Orange Juice and Hesperetin Supplementation to Hyperuricemic Rats Alter Oxidative Stress Markers and Xanthine Oxidoreductase Activity
Identifieur interne : 001009 ( Pmc/Corpus ); précédent : 001008; suivant : 001010Orange Juice and Hesperetin Supplementation to Hyperuricemic Rats Alter Oxidative Stress Markers and Xanthine Oxidoreductase Activity
Auteurs : Fatemeh Haidari ; Seid Ali Keshavarz ; Mohammad Reza Rashidi ; Majid Mohammad ShahiSource :
- Journal of Clinical Biochemistry and Nutrition [ 0912-0009 ] ; 2009.
Abstract
Our objective was to examine the effect of orange juice and hesperetin on serum total antioxidant capacity (TAC), lipid peroxidation (MDA), uric acid and hepatic xanthine oxidase (XO) and xanthine dehydrogenase (XDH) activity in hyperuricemic rats. Experimentally hyperuricemia in rats was induced by intraperitoneal injection of potassium oxonate (250 mg/kg). Orange juice (5 ml/kg) and hesperetin (5 mg/kg) was given by oral gavage to rats for 2 weeks and biochemical data was measured. Data showed that orange juice supplementation increased serum TAC and decreased MDA concentration (
Url:
DOI: 10.3164/jcbn.09-15
PubMed: 19902018
PubMed Central: 2771249
Links to Exploration step
PMC:2771249Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Orange Juice and Hesperetin Supplementation to Hyperuricemic Rats Alter Oxidative Stress Markers and Xanthine Oxidoreductase Activity</title><author><name sortKey="Haidari, Fatemeh" sort="Haidari, Fatemeh" uniqKey="Haidari F" first="Fatemeh" last="Haidari">Fatemeh Haidari</name><affiliation><nlm:aff id="aff1">Nutrition Department of Para-Medical School, Ahvaz Jondishapur University of Medical Sciences, Ahvaz 61357-15794, Iran</nlm:aff></affiliation></author><author><name sortKey="Ali Keshavarz, Seid" sort="Ali Keshavarz, Seid" uniqKey="Ali Keshavarz S" first="Seid" last="Ali Keshavarz">Seid Ali Keshavarz</name><affiliation><nlm:aff id="aff2">Schools of Health and Institute of Public Health, Tehran University of Medical Science, Tehran 14176-14411, Iran</nlm:aff></affiliation></author><author><name sortKey="Reza Rashidi, Mohammad" sort="Reza Rashidi, Mohammad" uniqKey="Reza Rashidi M" first="Mohammad" last="Reza Rashidi">Mohammad Reza Rashidi</name><affiliation><nlm:aff id="aff3">Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz 51664-14766, Iran</nlm:aff></affiliation></author><author><name sortKey="Mohammad Shahi, Majid" sort="Mohammad Shahi, Majid" uniqKey="Mohammad Shahi M" first="Majid" last="Mohammad Shahi">Majid Mohammad Shahi</name><affiliation><nlm:aff id="aff1">Nutrition Department of Para-Medical School, Ahvaz Jondishapur University of Medical Sciences, Ahvaz 61357-15794, Iran</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19902018</idno><idno type="pmc">2771249</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771249</idno><idno type="RBID">PMC:2771249</idno><idno type="doi">10.3164/jcbn.09-15</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">001009</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Orange Juice and Hesperetin Supplementation to Hyperuricemic Rats Alter Oxidative Stress Markers and Xanthine Oxidoreductase Activity</title><author><name sortKey="Haidari, Fatemeh" sort="Haidari, Fatemeh" uniqKey="Haidari F" first="Fatemeh" last="Haidari">Fatemeh Haidari</name><affiliation><nlm:aff id="aff1">Nutrition Department of Para-Medical School, Ahvaz Jondishapur University of Medical Sciences, Ahvaz 61357-15794, Iran</nlm:aff></affiliation></author><author><name sortKey="Ali Keshavarz, Seid" sort="Ali Keshavarz, Seid" uniqKey="Ali Keshavarz S" first="Seid" last="Ali Keshavarz">Seid Ali Keshavarz</name><affiliation><nlm:aff id="aff2">Schools of Health and Institute of Public Health, Tehran University of Medical Science, Tehran 14176-14411, Iran</nlm:aff></affiliation></author><author><name sortKey="Reza Rashidi, Mohammad" sort="Reza Rashidi, Mohammad" uniqKey="Reza Rashidi M" first="Mohammad" last="Reza Rashidi">Mohammad Reza Rashidi</name><affiliation><nlm:aff id="aff3">Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz 51664-14766, Iran</nlm:aff></affiliation></author><author><name sortKey="Mohammad Shahi, Majid" sort="Mohammad Shahi, Majid" uniqKey="Mohammad Shahi M" first="Majid" last="Mohammad Shahi">Majid Mohammad Shahi</name><affiliation><nlm:aff id="aff1">Nutrition Department of Para-Medical School, Ahvaz Jondishapur University of Medical Sciences, Ahvaz 61357-15794, Iran</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Clinical Biochemistry and Nutrition</title><idno type="ISSN">0912-0009</idno><idno type="eISSN">1880-5086</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Our objective was to examine the effect of orange juice and hesperetin on serum total antioxidant capacity (TAC), lipid peroxidation (MDA), uric acid and hepatic xanthine oxidase (XO) and xanthine dehydrogenase (XDH) activity in hyperuricemic rats. Experimentally hyperuricemia in rats was induced by intraperitoneal injection of potassium oxonate (250 mg/kg). Orange juice (5 ml/kg) and hesperetin (5 mg/kg) was given by oral gavage to rats for 2 weeks and biochemical data was measured. Data showed that orange juice supplementation increased serum TAC and decreased MDA concentration (<italic>p</italic>≤0.05). Orange juice also inhibited hepatic XO and XDH activity and decreased serum uric acid levels. Hesperetin, which is the main flavanone constituent in orange juice, also exhibited antioxidative and antihyperuricemic properties, but its effect was weaker than that of orange juice. Although the hypouricemic effect of allopurinol (5 mg/kg), as a positive control, was much higher than that of orange juice and hesperetin, it could not significantly change biomarkers of oxidative stress. These features of orange juice and hesperetin make them an attractive candidate for the prophylactic treatment of hyperuricaemia, particularly if these compounds are to be taken on a long-term basis.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Mo, S F" uniqKey="Mo S">S.F. Mo</name></author><author><name sortKey="Zhou, F" uniqKey="Zhou F">F. Zhou</name></author><author><name sortKey="Lv, Y Z" uniqKey="Lv Y">Y.Z. Lv</name></author><author><name sortKey="Hu, Q H" uniqKey="Hu Q">Q.H. Hu</name></author><author><name sortKey="Zhang, D M" uniqKey="Zhang D">D.M. Zhang</name></author><author><name sortKey="Kong, L D" uniqKey="Kong L">L.D. Kong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Strazzullo, P" uniqKey="Strazzullo P">P. Strazzullo</name></author><author><name sortKey="Puig, J G" uniqKey="Puig J">J.G. Puig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Liote, F" uniqKey="Liote F">F. Liote</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nguyen, M T" uniqKey="Nguyen M">M.T. Nguyen</name></author><author><name sortKey="Awale, S" uniqKey="Awale S">S. Awale</name></author><author><name sortKey="Tezuka, Y" uniqKey="Tezuka Y">Y. Tezuka</name></author><author><name sortKey="Tran, Q L" uniqKey="Tran Q">Q.L. Tran</name></author><author><name sortKey="Watanabe, H" uniqKey="Watanabe H">H. Watanabe</name></author><author><name sortKey="Kadota, S" uniqKey="Kadota S">S. Kadota</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Maia, L" uniqKey="Maia L">L. Maia</name></author><author><name sortKey="Duarte, R O" uniqKey="Duarte R">R.O. Duarte</name></author><author><name sortKey="Ponces Freire, A" uniqKey="Ponces Freire A">A. Ponces-Freire</name></author><author><name sortKey="Moura, J J" uniqKey="Moura J">J.J. Moura</name></author><author><name sortKey="Mira, L" uniqKey="Mira L">L. Mira</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choi, E J" uniqKey="Choi E">E.J. Choi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fels, E" uniqKey="Fels E">E. Fels</name></author><author><name sortKey="Sundy, J S" uniqKey="Sundy J">J.S. Sundy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Zhu, J X" uniqKey="Zhu J">J.X. Zhu</name></author><author><name sortKey="Kong, L D" uniqKey="Kong L">L.D. Kong</name></author><author><name sortKey="Yang, C" uniqKey="Yang C">C. Yang</name></author><author><name sortKey="Cheng, C H" uniqKey="Cheng C">C.H. Cheng</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kinoshita, T" uniqKey="Kinoshita T">T. Kinoshita</name></author><author><name sortKey="Lepp, Z" uniqKey="Lepp Z">Z. Lepp</name></author><author><name sortKey="Kawai, Y" uniqKey="Kawai Y">Y. Kawai</name></author><author><name sortKey="Terao, J" uniqKey="Terao J">J. Terao</name></author><author><name sortKey="Chuman, H" uniqKey="Chuman H">H. Chuman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rackova, L" uniqKey="Rackova L">L. Rackova</name></author><author><name sortKey="Oblozinsky, M" uniqKey="Oblozinsky M">M. Oblozinsky</name></author><author><name sortKey="Kostalova, D" uniqKey="Kostalova D">D. Kostalova</name></author><author><name sortKey="Kettmann, V" uniqKey="Kettmann V">V. Kettmann</name></author><author><name sortKey="Bezakova, L" uniqKey="Bezakova L">L. Bezakova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lin, C M" uniqKey="Lin C">C.M. Lin</name></author><author><name sortKey="Chen, C S" uniqKey="Chen C">C.S. Chen</name></author><author><name sortKey="Chen, C T" uniqKey="Chen C">C.T. Chen</name></author><author><name sortKey="Liang, Y C" uniqKey="Liang Y">Y.C. Liang</name></author><author><name sortKey="Lin, J K" uniqKey="Lin J">J.K. Lin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Potapovich, A I" uniqKey="Potapovich A">A.I. Potapovich</name></author><author><name sortKey="Kostyuk, V A" uniqKey="Kostyuk V">V.A. Kostyuk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choi, E J" uniqKey="Choi E">E.J. Choi</name></author><author><name sortKey="Kim, G D" uniqKey="Kim G">G.D. Kim</name></author><author><name sortKey="Chee, K M" uniqKey="Chee K">K.M. Chee</name></author><author><name sortKey="Kim, G H" uniqKey="Kim G">G.H. Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kaur, G" uniqKey="Kaur G">G. Kaur</name></author><author><name sortKey="Tirkey, N" uniqKey="Tirkey N">N. Tirkey</name></author><author><name sortKey="Chopra, K" uniqKey="Chopra K">K. Chopra</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Proteggente, A R" uniqKey="Proteggente A">A.R. Proteggente</name></author><author><name sortKey="Saija, A" uniqKey="Saija A">A. Saija</name></author><author><name sortKey="De Pasquale, A" uniqKey="De Pasquale A">A. De Pasquale</name></author><author><name sortKey="Rice Evans, C A" uniqKey="Rice Evans C">C.A. Rice-Evans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cirico, T L" uniqKey="Cirico T">T.L. Cirico</name></author><author><name sortKey="Omaye, S T" uniqKey="Omaye S">S.T. Omaye</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jung, U J" uniqKey="Jung U">U.J. Jung</name></author><author><name sortKey="Kim, H J" uniqKey="Kim H">H.J. Kim</name></author><author><name sortKey="Lee, J S" uniqKey="Lee J">J.S. Lee</name></author><author><name sortKey="Lee, M K" uniqKey="Lee M">M.K. Lee</name></author><author><name sortKey="Kim, H O" uniqKey="Kim H">H.O. Kim</name></author><author><name sortKey="Park, E J" uniqKey="Park E">E.J. Park</name></author><author><name sortKey="Kim, H K" uniqKey="Kim H">H.K. Kim</name></author><author><name sortKey="Jeong, T S" uniqKey="Jeong T">T.S. Jeong</name></author><author><name sortKey="Choi, M S" uniqKey="Choi M">M.S. Choi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hall, I H" uniqKey="Hall I">I.H. Hall</name></author><author><name sortKey="Scoville, J P" uniqKey="Scoville J">J.P. Scoville</name></author><author><name sortKey="Reynolds, D J" uniqKey="Reynolds D">D.J. Reynolds</name></author><author><name sortKey="Simlot, R" uniqKey="Simlot R">R. Simlot</name></author><author><name sortKey="Duncan, P" uniqKey="Duncan P">P. Duncan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prajda, N" uniqKey="Prajda N">N. Prajda</name></author><author><name sortKey="Weber, G" uniqKey="Weber G">G. Weber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Benzie, I F" uniqKey="Benzie I">I.F. Benzie</name></author><author><name sortKey="Strain, J J" uniqKey="Strain J">J.J. Strain</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yoshioka, T" uniqKey="Yoshioka T">T. Yoshioka</name></author><author><name sortKey="Kawada, K" uniqKey="Kawada K">K. Kawada</name></author><author><name sortKey="Shimada, T" uniqKey="Shimada T">T. Shimada</name></author><author><name sortKey="Mori, M" uniqKey="Mori M">M. Mori</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nuki, G" uniqKey="Nuki G">G. Nuki</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kong, L D" uniqKey="Kong L">L.D. Kong</name></author><author><name sortKey="Yang, C" uniqKey="Yang C">C. Yang</name></author><author><name sortKey="Ge, F" uniqKey="Ge F">F. Ge</name></author><author><name sortKey="Wang, H D" uniqKey="Wang H">H.D. Wang</name></author><author><name sortKey="Guo, Y S" uniqKey="Guo Y">Y.S. Guo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, J X" uniqKey="Zhu J">J.X. Zhu</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y. Wang</name></author><author><name sortKey="Kong, L D" uniqKey="Kong L">L.D. Kong</name></author><author><name sortKey="Yang, C" uniqKey="Yang C">C. Yang</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X. Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, W Y" uniqKey="Lee W">W.Y. Lee</name></author><author><name sortKey="Lee, S M" uniqKey="Lee S">S.M. Lee</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moon, Y J" uniqKey="Moon Y">Y.J. Moon</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X. Wang</name></author><author><name sortKey="Morris, M E" uniqKey="Morris M">M.E. Morris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vijayalakshmi, B" uniqKey="Vijayalakshmi B">B. Vijayalakshmi</name></author><author><name sortKey="Chandrasekhar, M" uniqKey="Chandrasekhar M">M. Chandrasekhar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Johnson, R J" uniqKey="Johnson R">R.J. Johnson</name></author><author><name sortKey="Kang, D H" uniqKey="Kang D">D.H. Kang</name></author><author><name sortKey="Feig, D" uniqKey="Feig D">D. Feig</name></author><author><name sortKey="Kivlighn, S" uniqKey="Kivlighn S">S. Kivlighn</name></author><author><name sortKey="Kanellis, J" uniqKey="Kanellis J">J. Kanellis</name></author><author><name sortKey="Watanabe, S" uniqKey="Watanabe S">S. Watanabe</name></author><author><name sortKey="Tuttle, K R" uniqKey="Tuttle K">K.R. Tuttle</name></author><author><name sortKey="Rodriguez Iturbe, B" uniqKey="Rodriguez Iturbe B">B. Rodriguez-Iturbe</name></author><author><name sortKey="Herrera Acosta, J" uniqKey="Herrera Acosta J">J. Herrera-Acosta</name></author><author><name sortKey="Mazzali, M" uniqKey="Mazzali M">M. Mazzali</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ross, J A" uniqKey="Ross J">J.A. Ross</name></author><author><name sortKey="Kasum, C M" uniqKey="Kasum C">C.M. Kasum</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stinefelt, B" uniqKey="Stinefelt B">B. Stinefelt</name></author><author><name sortKey="Leonard, S S" uniqKey="Leonard S">S.S. Leonard</name></author><author><name sortKey="Blemings, K P" uniqKey="Blemings K">K.P. Blemings</name></author><author><name sortKey="Shi, X" uniqKey="Shi X">X. Shi</name></author><author><name sortKey="Klandorf, H" uniqKey="Klandorf H">H. Klandorf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, X" uniqKey="Zhao X">X. Zhao</name></author><author><name sortKey="Zhu, J X" uniqKey="Zhu J">J.X. Zhu</name></author><author><name sortKey="Mo, S F" uniqKey="Mo S">S.F. Mo</name></author><author><name sortKey="Pan, Y" uniqKey="Pan Y">Y. Pan</name></author><author><name sortKey="Kong, L D" uniqKey="Kong L">L.D. Kong</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">J Clin Biochem Nutr</journal-id><journal-id journal-id-type="publisher-id">JCBN</journal-id><journal-title-group><journal-title>Journal of Clinical Biochemistry and Nutrition</journal-title></journal-title-group><issn pub-type="ppub">0912-0009</issn><issn pub-type="epub">1880-5086</issn><publisher><publisher-name>the Society for Free Radical Research Japan</publisher-name><publisher-loc>Kyoto, Japan</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">19902018</article-id><article-id pub-id-type="pmc">2771249</article-id><article-id pub-id-type="publisher-id">jcbn09-15</article-id><article-id pub-id-type="doi">10.3164/jcbn.09-15</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Article</subject></subj-group></article-categories><title-group><article-title>Orange Juice and Hesperetin Supplementation to Hyperuricemic Rats Alter Oxidative Stress Markers and Xanthine Oxidoreductase Activity</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Haidari</surname><given-names>Fatemeh</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib><contrib contrib-type="author"><name><surname>Ali Keshavarz</surname><given-names>Seid</given-names></name><xref ref-type="aff" rid="aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Reza Rashidi</surname><given-names>Mohammad</given-names></name><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Mohammad Shahi</surname><given-names>Majid</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Nutrition Department of Para-Medical School, Ahvaz Jondishapur University of Medical Sciences, Ahvaz 61357-15794, Iran</aff><aff id="aff2"><label>2</label>Schools of Health and Institute of Public Health, Tehran University of Medical Science, Tehran 14176-14411, Iran</aff><aff id="aff3"><label>3</label>Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz 51664-14766, Iran</aff><author-notes><corresp id="cor1">*To whom correspondence should be addressed. Tel: +98-611-3367550 Fax: +98-611-3367550 E-mail: <email>haidari58@gmail.com</email></corresp></author-notes><pub-date pub-type="ppub"><month>11</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>28</day><month>10</month><year>2009</year></pub-date><volume>45</volume><issue>3</issue><fpage>285</fpage><lpage>291</lpage><history><date date-type="received"><day>13</day><month>2</month><year>2009</year></date><date date-type="accepted"><day>20</day><month>3</month><year>2009</year></date></history><permissions><copyright-statement>Copyright © 2009 JCBN</copyright-statement><copyright-year>2009</copyright-year><license license-type="open-access"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>Our objective was to examine the effect of orange juice and hesperetin on serum total antioxidant capacity (TAC), lipid peroxidation (MDA), uric acid and hepatic xanthine oxidase (XO) and xanthine dehydrogenase (XDH) activity in hyperuricemic rats. Experimentally hyperuricemia in rats was induced by intraperitoneal injection of potassium oxonate (250 mg/kg). Orange juice (5 ml/kg) and hesperetin (5 mg/kg) was given by oral gavage to rats for 2 weeks and biochemical data was measured. Data showed that orange juice supplementation increased serum TAC and decreased MDA concentration (<italic>p</italic>≤0.05). Orange juice also inhibited hepatic XO and XDH activity and decreased serum uric acid levels. Hesperetin, which is the main flavanone constituent in orange juice, also exhibited antioxidative and antihyperuricemic properties, but its effect was weaker than that of orange juice. Although the hypouricemic effect of allopurinol (5 mg/kg), as a positive control, was much higher than that of orange juice and hesperetin, it could not significantly change biomarkers of oxidative stress. These features of orange juice and hesperetin make them an attractive candidate for the prophylactic treatment of hyperuricaemia, particularly if these compounds are to be taken on a long-term basis.</p></abstract><kwd-group><kwd>antioxidant</kwd><kwd>flavonoids</kwd><kwd>uric acid</kwd><kwd>xanthine oxidase</kwd></kwd-group></article-meta></front><body><sec sec-type="introduction"><title>Introduction</title><p>Hyperuricemia, characterized by abnormal high levels of uric acid, is a common metabolic disorder with a worldwide distribution [<xref ref-type="bibr" rid="B1">1</xref>]. It has been considered as an important risk factor for gout and may be associated with oxidative stress conditions [<xref ref-type="bibr" rid="B2">2</xref>]. That is way the control of uric acid production has been widely considered as a key factor in the prevention and treatment of these diseases [<xref ref-type="bibr" rid="B3">3</xref>]. Xanthine oxidoreductase (XOR), a molybdenum-containing enzyme, is the key enzyme in the catabolism of purines; that catalyses the oxidative hydroxylation of hypoxanthine to xanthine and xanthine to the terminal catabolite uric acid [<xref ref-type="bibr" rid="B4">4</xref>]. It is worth noting that XOR occurs in two different forms. Xanthine dehydrogenase (XDH) is the prevalent operative form under physiological conditions and has greater affinity for oxidized nicotinamide adenine dinucleotide (NAD<sup>+</sup>) compared to oxygen, as the electron acceptor. Under pathological conditions, however, in parallel to the degradation of ATP into adenine and xanthine, an extensive conversion of XDH to xanthine oxidase (XO) takes place. The latter uses molecular oxygen in place of NAD<sup>+</sup> as electron acceptor and leads to the formation of superoxide anion and hydrogen peroxide in parallel with uric acid production. Therefore, XOR can act as a source of reactive oxygen species (ROS) [<xref ref-type="bibr" rid="B5">5</xref>]. ROS may be involved in the pathogenesis of various degenerative diseases because they induce damage to biological macromolecules such as proteins, fats and DNA [<xref ref-type="bibr" rid="B6">6</xref>]. That is way the inhibition of XOR activity may be decrease the level of uric acid and ROS production, and results in anti-hyperuricemic and antioxidative effects.</p><p>Allopurinol is the sole XOR inhibitor under the clinical application and has served as a dominant uric acid-lowering agent in the past three decades [<xref ref-type="bibr" rid="B7">7</xref>]. However, some severe adverse effects such as hepatitis, nephropathy and allergic reactions limit the clinical use of allopurinol and it would be highly desired to search for new XOR inhibitors, in particular from natural sources, as alternatives for allopurinol [<xref ref-type="bibr" rid="B2">2</xref>, <xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B8">8</xref>].</p><p>Flavonoids are non-nutrient polyphenolic compounds that occur in edible plants and consist of six major classes based on specific structural differences: flavonols, flavones, flavanones, catechins, anthocyanidins, and isoflavones. Flavonoids possess a wide range of biochemical and pharmacological effects and have been recommended as chemopreventive agents or nutritional supplements [<xref ref-type="bibr" rid="B6">6</xref>, <xref ref-type="bibr" rid="B9">9</xref>]. The predominant mechanism of their biological actions is thought to result from antioxidant activity, enzyme inhibition, and the capacity to scavenge free radicals [<xref ref-type="bibr" rid="B10">10</xref>, <xref ref-type="bibr" rid="B11">11</xref>]. XOR is one of the most important enzymes that are inhibited by some flavonoids [<xref ref-type="bibr" rid="B12">12</xref>].</p><p>Hesperetin (3',5,7-trihydroxy-4'-methoxyflavanone), which occurs as hesperidin (its glycoside form) in nature, belongs to flavanone subclass of flavonoids and is mainly found in citrus fruits such as orange [<italic>13</italic>,<italic> 14</italic>]. There is significant interest in the direct antioxidant activities of citrus flavanones hesperidin and hesperetin, due to associations between consumption of flavanone-rich fruits, such as orange and decreased incidence of oxidative stress related disease [<xref ref-type="bibr" rid="B15">15</xref>–<xref ref-type="bibr" rid="B17">17</xref>]. However, indirect antioxidant action, such as the inhibition of ROS-producing enzymes, may be equally relevant to health benefits through a general reduction in oxidative stress <italic>in vivo</italic>. Although hesperetin produced from hesperidin is actually bioactive molecule in the body, only a few <italic>in vitro</italic> and <italic>in vivo</italic> studies have assessed hesperetin, rather than hesperidin.</p><p>In this study, the effects of orange juice and hesperetin on the <italic>in vivo</italic> activity of XO and XDH and serum uric acid levels were assessed in oxonate-induced hyperuricemic rats, many for the first time. The possible role of those in reducing biomarkers of oxidative stress was also investigated.</p></sec><sec sec-type="materials and methods"><title>Materials and Methods</title><sec><title>Chemicals</title><p>Hesperetin, potassium oxonate, xanthine, NAD<sup>+</sup>, uric acid, allopurinol, tetraethoxypropane (TEP), trichloroacetic acid (TCA), 2-thiobarbituric acid (TBA), bicinchoninic acid kit and 6-mercaptopurine were purchased from Sigma-Aldrich Chemical Co. (Steinheim, Germany). All other reagents used were from of analytical grades. Orange (<italic>Citrus sinensis</italic> L.) was purchased from a wholesale market.</p></sec><sec><title>Test compound preparation</title><p>Orange is commonly peeled and squeezed for its juice. Hesperetin was first dissolved in propylene glycol and then added 0.9% saline (1:20 V:V). Allopurinol used as a positive control, was prepared in 0.9% saline.</p></sec><sec><title>Animals</title><p>A total of 30 male Wistar rats (body weights: 180–200 g) were obtained from the animal house of Tabriz University of Medical Sciences, Iran. They were fed with a commercial laboratory diet and allowed food and water ad libitum for an acclimatization period of 1 week prior to the experiment. All animals were maintained on a 12 h/12 h light/dark cycle and the temperature and humidity were kept at 18 ± 1°C and 50%, respectively. They were handled according to the recommendation of the local and national ethic committees.</p></sec><sec><title>Animal model of hyperuricemia in rats</title><p>Experimentally-induced hyperuricemia in rats (due to inhibition of uricase with potassium oxonate) was used to study anti-hyperuricemic and antioxidant effects of test compounds [<xref ref-type="bibr" rid="B18">18</xref>]. Briefly, 250 mg/kg potassium oxonate (PO) dissolved in 0.9% saline solution was administrated intraperitonially to each animal 1 h before oral administration of test compounds.</p></sec><sec><title>Experimental design</title><p>This study was conducted from April 2008 to Oct 2008. Rats were randomly divided into five equal groups (6 rats per group). In group 1, the normal group, each animal received only water as vehicle. In group 2, the hyperurecemic control group, uricase inhibitor PO (250 mg/kg) was administrated intraperitoneally. In groups 3, 4 and 5, each animal received the same dose of PO 1 h before administration of 5 ml/kg orange juice, 5 mg/kg hesperetin and 5 mg/kg allopurinol, respectively. The freshly prepared samples were administrated to corresponding groups by oral gavage once a day for 2 weeks.</p></sec><sec><title>Sample preparation</title><p>At the end of the experiment, rats were anesthetized between 09.00 and 10.00 am. Blood was taken from the abdominal aorta 1 h after the test compound administration. Serum was obtained by centrifuging blood sample at 6000 g for 10 min. For the high performance liquid chromatography (HPLC) analysis, the serum was filtered using SPARTAN 13/0.45 RC, Watman (USA). The sera were stored at −20°C until use.</p><p>After blood sampling, livers were removed, weighed and then rapidly washed in 0.9% cold saline and placed in ice-cold isotonic potassium chloride solution (1.15% KCl w/v) containing 0.1 mM EDTA. The livers were then chopped into 4–5 volumes of 50 mM phosphate buffer (pH 7.4) and homogenized by a homogenizer fitted with a Teflon pestle. The homogenate was then centrifuged at 3000 g for 10 min, the lipid layer was carefully removed, and the resulting supernatant fraction was further centrifuged at 15,000 g for 60 min at 4°C. The supernatant stored at −80°C until use.</p></sec><sec><title>Uric acid determination</title><p>The serum uric acid levels were analyzed by HPLC method using a system supplied by Waters Associates (Northwich, Cheshire) which consisted of a Waters 515 pump, Waters 717 plus Autosampler, Waters 2487, Dual λ Absorbance Detector. The mobile phase was a mixture of 100 mM KH<sub>2</sub>PO<sub>4</sub> (pH 3.5): Methanol (97:3, v/v). Separations were performed on a C-18 column (Perfectsil Target ODS-3 (5 µm), 250 × 4.6 mm) with a C-18 guard column (Perfectsil Target ODS-3 (5 µm), 10 × 4 mm). The effluent was monitored by UV detection at 290 nm at a flow rate of 1.0 ml/min. Standard solutions of uric acid in the range of 10 to 1000 µM/L were prepared in mobile phase. Serum uric acid concentrations were expressed as µM/L. 6-Mercaptopurine (1 mM) was used as the internal standard. The percentage decrease in serum uric acid levels was calculated as [(<italic>C</italic>C–<italic>C</italic>T)/(<italic>C</italic>C–<italic>C</italic>N)] *100, where <italic>C</italic>C, <italic>C</italic>N, and <italic>C</italic>T are the uric acid concentrations (µM/L) of control (PO treated), normal (without PO treatment), and test (PO + test compounds treated) groups.</p></sec><sec><title>XO and XDH activities determination</title><p>The XO and XDH activities were measured spectrophotometrically by monitoring the production of uric acid from xanthine according to Prajda and Weber’s method [<xref ref-type="bibr" rid="B19">19</xref>]. In the case of XDH, the assay mixture consisted of 50 µM xanthine, 50 µM phosphate buffer (pH 7.4), 200 µM NAD<sup>+</sup>, and 100 µl of the enzyme solution. After preincubation at 37°C for 15 min, the reaction was initiated by the addition of the substrate solution. After 30 min, the reaction was terminated by adding 0.5 ml HCl (0.6 M), and the absorbance was measured at 290 nm using a Shimadzu 2550 UV/VIS spectrophotometer which was controlled by the Shimadzu UV Probe personal software package including kinetics software (Shimadzu, Kyoto, Japan). The instrument was connected to a Shimadzu cell temperature control unit. XO activity was measured using a similar method described for XDH with the difference being that molecular oxygen was used in place of NAD<sup>+</sup> as electron acceptor. One unit (U) of activity was defined as 1 nM of uric acid formed per minute at 37°C, pH 7.4.</p></sec><sec><title>Protein determination</title><p>Protein concentration was determined spectrophotometrically by bicinchoninic acid kit using bovine serum albumin as the standard.</p></sec><sec><title>Total antioxidant capacity (TAC) assay</title><p>Total serum antioxidant capacity assay was performed using TPTZ (tripyridyltriazine) reagent. This method measures the ability of the antioxidants contained in the sample to reduce ferrictripiridyltriazine (Fe<sup>3+</sup>-TPTZ) to a ferrous form (Fe<sup>2+</sup>) which absorbs light at 593 nm. TAC of serum was calculated by plotting a standard curve of absorbance against µM/L concentration of Fe<sup>2+</sup> standard solution [<xref ref-type="bibr" rid="B20">20</xref>].</p></sec><sec><title>Lipid peroxide determination</title><p>Lipid peroxide in the serum was measured according to the method of Yoshioka <italic>et al.</italic> [<xref ref-type="bibr" rid="B21">21</xref>].</p></sec><sec><title>Statistical analysis</title><p>All the samples and standards were run in duplicate and the results were expressed as means ± standard deviation (SD). The statistical comparison of each experimental group with control group was performed by Independent-sample <italic>t</italic> test using SPSS computer program. The probabilities of 5% or less (<italic>p</italic>≤0.05) were considered significant.</p></sec></sec><sec sec-type="results"><title>Results</title><p>As shown in Table <xref ref-type="table" rid="T1">1</xref>, potassium oxonate administration can lead to a decrease in serum total antioxidant capacity in hyperuricemic control rats compared to normal rats. As it is also obvious in Table <xref ref-type="table" rid="T1">1</xref>, a significant increase (<italic>p</italic>≤0.05) in serum total antioxidant capacity after orange juice administration compared to hyperuricemic control group (280 ± 30.16 vs 213 ± 65.92 µM/L) was observed.</p><p>As also shown in Table <xref ref-type="table" rid="T1">1</xref>, in hyperuricemic control rats, the level of serum malondialdehyde (MDA), as a biomarker of lipid peroxidation, was statistically higher than that of normal rats (<italic>p</italic>≤0.05). Orange juice administration was also significantly able to decrease MDA concentration compared to hyperuricemic control rats (<italic>p</italic>≤0.05). Hesperetin and Allopurinol treatment could not significantly increase serum total antioxidant capacity or decrease MDA concentration in this study (<italic>p</italic>≥0.05).</p><p>The effects of the orally administered orange juice and hesperetin on hepatic XO and XDH <italic>activity</italic> are shown in Table <xref ref-type="table" rid="T2">2</xref>. In oxonate-pretreated rats, orange juice and hesperetin resulted in significant inhibition on both hepatic XO and XDH activity. The inhibitory effect of orange juice on XO and XDH activity was 24.49% (<italic>p</italic>≤0.05) and 30.89% (<italic>p</italic>≤0.001), respectively. Hesperetin treatment caused 23.69% (<italic>p</italic>≤0.05) and 20.68% (<italic>p</italic>≤0.05) inhibition on XO and XDH activity, respectively. Allopurinol, as a positive control, significantly decreased the mean activity of XO and XDH, respectively by 57.83% (<italic>p</italic>≤0.001) and 66.75% (<italic>p</italic>≤0.001).</p><p>As shown in Fig. <xref ref-type="fig" rid="F1">1</xref>, intraperitoneal injection of potassium oxonate (250 mg/kg) to control group markedly increased the serum uric acid levels, and reached to 214.36 ± 26.42 (µM/L) at the end of the experiment. The uric acid level in normal rats was only 99.87 ± 17.44 (µM/L).</p><p>As also shown in Fig. <xref ref-type="fig" rid="F1">1</xref>, oral administration of orange juice and hesperetin significantly decreased the serum uric acid levels in hyperuricemic rats. The extents of reduction for orange juice and hesperetin were 38.76% and 24.93%, respectively. The reference drug allopurinol substantially reduced the uric acid level by 124%. It is worth to note that in present study, we found a positive correlation between serum uric acid levels and MDA concentration (Fig. <xref ref-type="fig" rid="F2">2</xref>).</p></sec><sec sec-type="Discussion"><title>Discussion</title><p>Hyperuricemia is a metabolic disorder which may play an important role in the development of gout and oxidative stress related disease such as cancer and cardiovascular diseases [<xref ref-type="bibr" rid="B2">2</xref>, <xref ref-type="bibr" rid="B22">22</xref>]. At the present, allopurinol, a purine analogue, which causes inhibition on XOR, is the only drug with clinical application to lower uric acid production [<xref ref-type="bibr" rid="B7">7</xref>]. Due to some serious side effects of this drug, many attempts are made to find a safer alternative for allopurinol particularly from natural sources [<xref ref-type="bibr" rid="B2">2</xref>, <xref ref-type="bibr" rid="B23">23</xref>–<xref ref-type="bibr" rid="B25">25</xref>].</p><p>Positive healthy effects of flavonoids and diets rich in these compounds have been reported in several diseases. Flavonoids have been described as health-promoting, disease-preventing dietary supplements because they are extremely safe and associates with low toxicity, making them to be excellent candidates for agents [<xref ref-type="bibr" rid="B26">26</xref>]. In the present <italic>in vivo</italic> investigation, the effects of orange juice (5 ml/kg) and hesperetin (5 mg/kg) on biomarkers of oxidative stress, serum uric acid levels and hepatic XO and XDH activity in oxonate-induced hyperuricemic rats were assessed, many for the first time.</p><p>Following treatment of the hyperuricemic rats with orange juice a significant increase (<italic>p</italic>≤0.05) in serum total antioxidant capacity compared to hyperuricemic control was found. Orange juice administration was also significantly able to decrease serum MDA levels, a marker of lipid peroxidation, compared to hyperuricemic control rats (<italic>p</italic>≤0.05). Flavonoids presenting in orange juice possess antioxidant properties and suppress destructive oxygen free radicals. An overabundance of free radicals can damage all components of the cell, including proteins, fats and DNA, contributing to the development of several pathological conditions [<xref ref-type="bibr" rid="B9">9</xref>, <xref ref-type="bibr" rid="B27">27</xref>].</p><p>In oxonate-pretreated control rats, a significant increase in serum MDA levels and decrease in serum total antioxidant capacity was found. Potassium oxonate, a selectively competitive uricase inhibitor, blocks the effect of hepatic uricase and produces hyperuricemia in rodents [<xref ref-type="bibr" rid="B18">18</xref>]. Increased uric acid level has been associated with increased production of oxygen free radicals, due to the conversion of XDH to XO that plays a pivotal role in progression of oxidative stress condition [<xref ref-type="bibr" rid="B5">5</xref>]. In present study, uric acid was positively correlated with MDA. XO is a source of ROS and may explain the link between hyperuricemia and oxidative stress-induced diseases [<xref ref-type="bibr" rid="B2">2</xref>, <xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B5">5</xref>]. Moreover, serum uric acid elevation may promote oxygenation of LDL-C and facilitate lipid peroxidation [<xref ref-type="bibr" rid="B28">28</xref>]. This capacity of XO makes the enzyme the focus of interest in many recent biochemical and clinical studies [<xref ref-type="bibr" rid="B5">5</xref>]. From the above discussion we can assume that serum uric acid through lipid peroxidation, might be working towards the etiopathogenesis of ROS-mediated diseases and its serum level may be a deciding factor for progression of the disease.</p><p>Our study also showed that orange juice has a higher potential than hesperetin to improve total antioxidant capacity and to reverse MDA. In orange, hesperidin (hesperetin 7-O-beta-rutinoside) is predominant and it is well known that the bioavailability of hesperidin in orange is higher than that of its aglycon [<xref ref-type="bibr" rid="B29">29</xref>]. Therefore, the higher efficiency of orange juice compared to hesperetin to improve biomarkers of oxidative stress could be attributed to its higher intestinal absorption. Furthermore, it is possible that the other flavonoids except hesperetin -studied in this investigation- to be responsible for the antioxidative effects of orange juice. In this study, allopurinol could not significantly increase total antioxidant capacity or decrease MDA concentration in hyperuricemic rats. However, the inhibition of XO by allopurinol was previously reported to decrease the level of ROS production and reduce the hepatic injury associated with liver transplantation [<xref ref-type="bibr" rid="B25">25</xref>].</p><p>We also showed that the orally administered orange juice (5 ml/kg) and hesperetin (5 mg/g) could significantly decrease the uric acid levels compared to hyperuricemic control rats, but the mean levels of uric acid in these treated animals were yet higher than that of normal values. In this study, we did not investigate the dose response effect of them. It is speculated that the higher dosage of orange juice and hesperetin may be more effective in this regards.</p><p>It is important to note that, orange juice was more potent than hesperetin to attenuate and or to reverse hyperuricemia. As it is mentioned before, the less bioavailability of hesperetin aglycon than that of hesperetin glycosides representing in orange juice may be responsible for this finding. However, the effect of allopurinol, as a reference drug on reducing uric acid level was even more potent and reached serum uric acid levels to a lower level than that of normal levels (72.38 ± 0.32 vs 99.87 ± 0.29 µM/L). On the other hand, this property of orange juice and hesperetin could be considered as an advantage for them. Although the elevated levels of uric acid in the circulation could give rise to gout and possibly other pathological conditions [<xref ref-type="bibr" rid="B22">22</xref>], the antioxidant action of uric acid, particularly its ability to inhibit DNA damage, is also well documented [<xref ref-type="bibr" rid="B30">30</xref>]. Thus, excessive lowering of the uric acid level in the circulation beyond that of the normal range might even be counter productive [<xref ref-type="bibr" rid="B8">8</xref>]. These data also indicated that orange juice and hesperetin might bring fewer side effects than allopurinol in treatment of hyperuricemia and oxidative stress related diseases.</p><p>In oxonate-pretreated rats, orange juice and hesperetin resulted in significant inhibition on both hepatic XO and XDH activity. Several <italic>in vitro</italic> studies confirmed the competitive inhibition of flavonoids such as hesperetin and naringenin on XDH and XO activity. Structure–activity relationships of flavonoids have been proposed for the enzyme inhibitory effect of them. Due to the presence of several hydroxyl moieties on the carbon atoms of the basic skeleton, flavonoids may interact with active site of XDH and XO and inhibit them [<xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B11">11</xref>]. Therefore the hypouricemic property of orange juice and hesperetin observed in this study could be explained by the inhibitory effect of them on XDH and XO activity; however, there is not apparently a parallel relationship between the extent of the hypouricemic action and the reduction in the enzyme activity. Therefore, the observed hypouricemic effect can not be entirely attributed to this mechanism. Similar results have been reported by others [<xref ref-type="bibr" rid="B8">8</xref>, <xref ref-type="bibr" rid="B23">23</xref>, <xref ref-type="bibr" rid="B24">24</xref>]. According to these studies, the involvement of other possible mechanisms such as enhanced uric acid clearance or actions on other purine metabolizing enzymes can not be ruled out [<xref ref-type="bibr" rid="B8">8</xref>, <xref ref-type="bibr" rid="B23">23</xref>]. This could be further supported by the existence of some hypouricemic compounds including natural products that are devoid of XDH and XO inhibitory activity [<xref ref-type="bibr" rid="B8">8</xref>, <xref ref-type="bibr" rid="B31">31</xref>].</p><p>In conclusion, orange juice and hesperetin prevented oxidative stress by enhancing total antioxidant capacity and decreasing lipid peroxidation. However, the hypouricemic and XOR inhibitory action of orange juice (5 ml/kg) and hesperetin (5 mg/kg) was significant in this study; but this effect was partially weak and they could not reach the uric acid levels to the normal values in hyperuricemic rats. The higher dosage of orange juice and hesperetin should be investigated later. As orange is the most frequently consumed fruit in almost throughout the world and can be used safely long-term, this natural food could be served as a possible alternative for allopurinol, or at least in combination therapy to minimize the side-effects of allopurinol. Further investigations to explore the effect of other components of orange (<italic>Citrus sinensis</italic> L.) and to define their clinical efficacy would be highly desirable. Furthermore, the search for safe anti-hyperuricemic and antioxidative foods and diets must continue.</p></sec></body><back><ack><title>Acknowledgment</title><p>The authors would like to acknowledge the financial support provided by Tehran University of Medical Sciences. The authors are also grateful for the technical help of School of Pharmacy of Tabriz University of Medical Sciences. This work was supported Financially by a grant from Tehran University of Medical Sciences (NO: 85-04-27-4935).</p></ack><ref-list><title>References</title><ref id="B1"><label>1</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Mo</surname><given-names>S.F.</given-names></name><name><surname>Zhou</surname><given-names>F.</given-names></name><name><surname>Lv</surname><given-names>Y.Z.</given-names></name><name><surname>Hu</surname><given-names>Q.H.</given-names></name><name><surname>Zhang</surname><given-names>D.M.</given-names></name><name><surname>Kong</surname><given-names>L.D.</given-names></name></person-group><article-title>Hypouricemic action of selected flavonoids in mice: structure–activity relationships</article-title><source>Biol. Pharm. Bull.</source><volume>30</volume><fpage>1551</fpage><lpage>1556</lpage><year>2007</year><pub-id pub-id-type="pmid">17666819</pub-id></mixed-citation></ref><ref id="B2"><label>2</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Strazzullo</surname><given-names>P.</given-names></name><name><surname>Puig</surname><given-names>J.G.</given-names></name></person-group><article-title>Uric acid and oxidative stress: relative impact on cardiovascular risk</article-title><source>Nutr. Metab. Cardiovasc. Dis.</source><volume>17</volume><fpage>409</fpage><lpage>414</lpage><year>2007</year><pub-id pub-id-type="pmid">17643880</pub-id></mixed-citation></ref><ref id="B3"><label>3</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Liote</surname><given-names>F.</given-names></name></person-group><article-title>Hyperuricemia and gout</article-title><source>Curr. Rheumatol. Rep.</source><volume>5</volume><fpage>227</fpage><lpage>234</lpage><year>2003</year><pub-id pub-id-type="pmid">12744816</pub-id></mixed-citation></ref><ref id="B4"><label>4</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nguyen</surname><given-names>M.T.</given-names></name><name><surname>Awale</surname><given-names>S.</given-names></name><name><surname>Tezuka</surname><given-names>Y.</given-names></name><name><surname>Tran</surname><given-names>Q.L.</given-names></name><name><surname>Watanabe</surname><given-names>H.</given-names></name><name><surname>Kadota</surname><given-names>S.</given-names></name></person-group><article-title>Xanthine oxidase inhibitory activity of Vietnames medicinal plants</article-title><source>Biol. Pharm. Bull.</source><volume>27</volume><fpage>1414</fpage><lpage>1421</lpage><year>2004</year><pub-id pub-id-type="pmid">15340229</pub-id></mixed-citation></ref><ref id="B5"><label>5</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Maia</surname><given-names>L.</given-names></name><name><surname>Duarte</surname><given-names>R.O.</given-names></name><name><surname>Ponces-Freire</surname><given-names>A.</given-names></name><name><surname>Moura</surname><given-names>J.J.</given-names></name><name><surname>Mira</surname><given-names>L.</given-names></name></person-group><article-title>NADH oxidase activity of rat and human liver xanthine oxidoreductase: potential role in superoxide production</article-title><source>J. Biol. Inorg. Chem.</source><volume>12</volume><fpage>777</fpage><lpage>787</lpage><year>2007</year><pub-id pub-id-type="pmid">17440754</pub-id></mixed-citation></ref><ref id="B6"><label>6</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Choi</surname><given-names>E.J.</given-names></name></person-group><article-title>Antioxidative effects of hesperetin against 7,12-dimethylbenz(a)anthracene-induced oxidative stress in mice</article-title><source>Life Sci.</source><volume>82</volume><fpage>1059</fpage><lpage>1064</lpage><year>2008</year><pub-id pub-id-type="pmid">18433790</pub-id></mixed-citation></ref><ref id="B7"><label>7</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fels</surname><given-names>E.</given-names></name><name><surname>Sundy</surname><given-names>J.S.</given-names></name></person-group><article-title>Refractory gout: what is it and what to do about it?</article-title><source>Curr. Opin. Rheumatol.</source><volume>20</volume><fpage>198</fpage><lpage>202</lpage><year>2008</year><pub-id pub-id-type="pmid">18349751</pub-id></mixed-citation></ref><ref id="B8"><label>8</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>Y.</given-names></name><name><surname>Zhu</surname><given-names>J.X.</given-names></name><name><surname>Kong</surname><given-names>L.D.</given-names></name><name><surname>Yang</surname><given-names>C.</given-names></name><name><surname>Cheng</surname><given-names>C.H.</given-names></name><name><surname>Zhang</surname><given-names>X.</given-names></name></person-group><article-title>Administration of procyanidins from grape seeds reduces serum uric acid levels and decreases hepatic xanthine dehydrogenase/oxidase activities in oxonate-treated mice</article-title><source>Basic Clin. Pharmacol. Toxicol.</source><volume>94</volume><fpage>232</fpage><lpage>237</lpage><year>2004</year><pub-id pub-id-type="pmid">15125693</pub-id></mixed-citation></ref><ref id="B9"><label>9</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kinoshita</surname><given-names>T.</given-names></name><name><surname>Lepp</surname><given-names>Z.</given-names></name><name><surname>Kawai</surname><given-names>Y.</given-names></name><name><surname>Terao</surname><given-names>J.</given-names></name><name><surname>Chuman</surname><given-names>H.</given-names></name></person-group><article-title>An integrated database of flavonoids</article-title><source>Biofactors</source><volume>26</volume><fpage>179</fpage><lpage>188</lpage><year>2006</year><pub-id pub-id-type="pmid">16971749</pub-id></mixed-citation></ref><ref id="B10"><label>10</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rackova</surname><given-names>L.</given-names></name><name><surname>Oblozinsky</surname><given-names>M.</given-names></name><name><surname>Kostalova</surname><given-names>D.</given-names></name><name><surname>Kettmann</surname><given-names>V.</given-names></name><name><surname>Bezakova</surname><given-names>L.</given-names></name></person-group><article-title>Free radical scavenging activity and lipoxygenase inhibition of Mahonia aquifolium extract and isoquinoline alkaloids</article-title><source>J. Inflamm.</source><volume>4</volume><fpage>15</fpage><lpage>22</lpage><year>2007</year></mixed-citation></ref><ref id="B11"><label>11</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lin</surname><given-names>C.M.</given-names></name><name><surname>Chen</surname><given-names>C.S.</given-names></name><name><surname>Chen</surname><given-names>C.T.</given-names></name><name><surname>Liang</surname><given-names>Y.C.</given-names></name><name><surname>Lin</surname><given-names>J.K.</given-names></name></person-group><article-title>Molecular modeling of flavonoids that inhibits xanthine oxidase</article-title><source>Biochem. Biophys. Res. Commun.</source><volume>294</volume><fpage>167</fpage><lpage>172</lpage><year>2002</year><pub-id pub-id-type="pmid">12054758</pub-id></mixed-citation></ref><ref id="B12"><label>12</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Potapovich</surname><given-names>A.I.</given-names></name><name><surname>Kostyuk</surname><given-names>V.A.</given-names></name></person-group><article-title>Comparative study of antioxidant properties and cytoprotective activity of flavonoids</article-title><source>Biochemistry</source><volume>68</volume><fpage>514</fpage><lpage>519</lpage><year>2003</year><pub-id pub-id-type="pmid">12882632</pub-id></mixed-citation></ref><ref id="B13"><label>13</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Choi</surname><given-names>E.J.</given-names></name><name><surname>Kim</surname><given-names>G.D.</given-names></name><name><surname>Chee</surname><given-names>K.M.</given-names></name><name><surname>Kim</surname><given-names>G.H.</given-names></name></person-group><article-title>Effects of hesperetin on vessel structure formation in mouse embryonic stem (mES) cells</article-title><source>Nutrition</source><volume>22</volume><fpage>947</fpage><lpage>951</lpage><year>2006</year><pub-id pub-id-type="pmid">16815676</pub-id></mixed-citation></ref><ref id="B14"><label>14</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kaur</surname><given-names>G.</given-names></name><name><surname>Tirkey</surname><given-names>N.</given-names></name><name><surname>Chopra</surname><given-names>K.</given-names></name></person-group><article-title>Beneficial effect of hesperidin on lipopolysaccharide-induced hepatotoxicity</article-title><source>Toxicology</source><volume>226</volume><fpage>152</fpage><lpage>160</lpage><year>2006</year><pub-id pub-id-type="pmid">16919860</pub-id></mixed-citation></ref><ref id="B15"><label>15</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Proteggente</surname><given-names>A.R.</given-names></name><name><surname>Saija</surname><given-names>A.</given-names></name><name><surname>De Pasquale</surname><given-names>A.</given-names></name><name><surname>Rice-Evans</surname><given-names>C.A.</given-names></name></person-group><article-title>The compositional characterisation and antioxidant activity of fresh juices from sicilian sweet orange (Citrus sinensis L. Osbeck) varieties</article-title><source>Free Radic. Res.</source><volume>37</volume><fpage>681</fpage><lpage>687</lpage><year>2003</year><pub-id pub-id-type="pmid">12868495</pub-id></mixed-citation></ref><ref id="B16"><label>16</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cirico</surname><given-names>T.L.</given-names></name><name><surname>Omaye</surname><given-names>S.T.</given-names></name></person-group><article-title>Additive or synergetic effects of phenolic compounds on human low density lipoprotein oxidation</article-title><source>Food Chem. Toxicol.</source><volume>44</volume><fpage>510</fpage><lpage>516</lpage><year>2006</year><pub-id pub-id-type="pmid">16216401</pub-id></mixed-citation></ref><ref id="B17"><label>17</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Jung</surname><given-names>U.J.</given-names></name><name><surname>Kim</surname><given-names>H.J.</given-names></name><name><surname>Lee</surname><given-names>J.S.</given-names></name><name><surname>Lee</surname><given-names>M.K.</given-names></name><name><surname>Kim</surname><given-names>H.O.</given-names></name><name><surname>Park</surname><given-names>E.J.</given-names></name><name><surname>Kim</surname><given-names>H.K.</given-names></name><name><surname>Jeong</surname><given-names>T.S.</given-names></name><name><surname>Choi</surname><given-names>M.S.</given-names></name></person-group><article-title>Naringin supplementation lowers plasma lipids and enhances erythrocyte antioxidant enzyme activities in hypercholesterolemic subjects</article-title><source>Clin. Nutr.</source><volume>22</volume><fpage>561</fpage><lpage>568</lpage><year>2003</year><pub-id pub-id-type="pmid">14613759</pub-id></mixed-citation></ref><ref id="B18"><label>18</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hall</surname><given-names>I.H.</given-names></name><name><surname>Scoville</surname><given-names>J.P.</given-names></name><name><surname>Reynolds</surname><given-names>D.J.</given-names></name><name><surname>Simlot</surname><given-names>R.</given-names></name><name><surname>Duncan</surname><given-names>P.</given-names></name></person-group><article-title>Substituted cyclic imides as potential anti-gout agents</article-title><source>Life Sci.</source><volume>46</volume><fpage>1923</fpage><lpage>1927</lpage><year>1990</year><pub-id pub-id-type="pmid">2362548</pub-id></mixed-citation></ref><ref id="B19"><label>19</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Prajda</surname><given-names>N.</given-names></name><name><surname>Weber</surname><given-names>G.</given-names></name></person-group><article-title>Malignant transformation-linked imbalance: decreased xanthine oxidase activity in hepatomas</article-title><source>FEBS Lett.</source><volume>59</volume><fpage>245</fpage><lpage>249</lpage><year>1975</year><pub-id pub-id-type="pmid">179860</pub-id></mixed-citation></ref><ref id="B20"><label>20</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Benzie</surname><given-names>I.F.</given-names></name><name><surname>Strain</surname><given-names>J.J.</given-names></name></person-group><article-title>The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay</article-title><source>Anal. Biochem.</source><volume>239</volume><fpage>70</fpage><lpage>76</lpage><year>1996</year><pub-id pub-id-type="pmid">8660627</pub-id></mixed-citation></ref><ref id="B21"><label>21</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Yoshioka</surname><given-names>T.</given-names></name><name><surname>Kawada</surname><given-names>K.</given-names></name><name><surname>Shimada</surname><given-names>T.</given-names></name><name><surname>Mori</surname><given-names>M.</given-names></name></person-group><article-title>Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood</article-title><source>Am. J. Obstet. Gynecol.</source><volume>135</volume><fpage>372</fpage><lpage>376</lpage><year>1979</year><pub-id pub-id-type="pmid">484629</pub-id></mixed-citation></ref><ref id="B22"><label>22</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Nuki</surname><given-names>G.</given-names></name></person-group><article-title>Gout</article-title><source>Medicine</source><volume>34</volume><fpage>417</fpage><lpage>423</lpage><year>2006</year></mixed-citation></ref><ref id="B23"><label>23</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kong</surname><given-names>L.D.</given-names></name><name><surname>Yang</surname><given-names>C.</given-names></name><name><surname>Ge</surname><given-names>F.</given-names></name><name><surname>Wang</surname><given-names>H.D.</given-names></name><name><surname>Guo</surname><given-names>Y.S.</given-names></name></person-group><article-title>A Chinese herbal medicine Ermiao wan reduces serum uric acid level and inhibits liver xanthine dehydrogenase and xanthine oxidase in mice</article-title><source>J. Ethnopharmacol.</source><volume>93</volume><fpage>325</fpage><lpage>330</lpage><year>2004</year><pub-id pub-id-type="pmid">15234772</pub-id></mixed-citation></ref><ref id="B24"><label>24</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhu</surname><given-names>J.X.</given-names></name><name><surname>Wang</surname><given-names>Y.</given-names></name><name><surname>Kong</surname><given-names>L.D.</given-names></name><name><surname>Yang</surname><given-names>C.</given-names></name><name><surname>Zhang</surname><given-names>X.</given-names></name></person-group><article-title>Effects of Biota orientalis extract and its flavonoid constituents, quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver</article-title><source>J. Ethnopharmacol.</source><volume>93</volume><fpage>133</fpage><lpage>140</lpage><year>2004</year><pub-id pub-id-type="pmid">15182918</pub-id></mixed-citation></ref><ref id="B25"><label>25</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>W.Y.</given-names></name><name><surname>Lee</surname><given-names>S.M.</given-names></name></person-group><article-title>Synergistic protective effect of ischemic preconditioning and allopurinol on ischemia/reperfusion injury in rat liver</article-title><source>Biochem. Biophys. Res. Commun.</source><volume>349</volume><fpage>1087</fpage><lpage>1093</lpage><year>2006</year><pub-id pub-id-type="pmid">16959212</pub-id></mixed-citation></ref><ref id="B26"><label>26</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Moon</surname><given-names>Y.J.</given-names></name><name><surname>Wang</surname><given-names>X.</given-names></name><name><surname>Morris</surname><given-names>M.E.</given-names></name></person-group><article-title>Dietary flavonoids: effects on xenobiotic and carcinogen metabolism</article-title><source>Toxicol. In Vitro</source><volume>20</volume><fpage>187</fpage><lpage>210</lpage><year>2006</year><pub-id pub-id-type="pmid">16289744</pub-id></mixed-citation></ref><ref id="B27"><label>27</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vijayalakshmi</surname><given-names>B.</given-names></name><name><surname>Chandrasekhar</surname><given-names>M.</given-names></name></person-group><article-title>Oxidative stress and their resultant products as the target molecules in clinical diagnosis of age related disease</article-title><source>Curr. Trends Biotechnol. Pharm.</source><volume>2</volume><fpage>239</fpage><lpage>250</lpage><year>2008</year></mixed-citation></ref><ref id="B28"><label>28</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Johnson</surname><given-names>R.J.</given-names></name><name><surname>Kang</surname><given-names>D.H.</given-names></name><name><surname>Feig</surname><given-names>D.</given-names></name><name><surname>Kivlighn</surname><given-names>S.</given-names></name><name><surname>Kanellis</surname><given-names>J.</given-names></name><name><surname>Watanabe</surname><given-names>S.</given-names></name><name><surname>Tuttle</surname><given-names>K.R.</given-names></name><name><surname>Rodriguez-Iturbe</surname><given-names>B.</given-names></name><name><surname>Herrera-Acosta</surname><given-names>J.</given-names></name><name><surname>Mazzali</surname><given-names>M.</given-names></name></person-group><article-title>Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease?</article-title><source>Hypertension</source><volume>41</volume><fpage>1183</fpage><lpage>1190</lpage><year>2003</year><pub-id pub-id-type="pmid">12707287</pub-id></mixed-citation></ref><ref id="B29"><label>29</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ross</surname><given-names>J.A.</given-names></name><name><surname>Kasum</surname><given-names>C.M.</given-names></name></person-group><article-title>Dietary flavonoids: bioavailability, metabolic effects, and safety</article-title><source>Annu. Rev. Nutr.</source><volume>22</volume><fpage>19</fpage><lpage>34</lpage><year>2002</year><pub-id pub-id-type="pmid">12055336</pub-id></mixed-citation></ref><ref id="B30"><label>30</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Stinefelt</surname><given-names>B.</given-names></name><name><surname>Leonard</surname><given-names>S.S.</given-names></name><name><surname>Blemings</surname><given-names>K.P.</given-names></name><name><surname>Shi</surname><given-names>X.</given-names></name><name><surname>Klandorf</surname><given-names>H.</given-names></name></person-group><article-title>Free radical scavenging, DNA protection, and inhibition of lipid peroxidation mediated by uric acid</article-title><source>Ann. Clin. Lab. Sci.</source><volume>35</volume><fpage>37</fpage><lpage>45</lpage><year>2005</year><pub-id pub-id-type="pmid">15830708</pub-id></mixed-citation></ref><ref id="B31"><label>31</label><mixed-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhao</surname><given-names>X.</given-names></name><name><surname>Zhu</surname><given-names>J.X.</given-names></name><name><surname>Mo</surname><given-names>S.F.</given-names></name><name><surname>Pan</surname><given-names>Y.</given-names></name><name><surname>Kong</surname><given-names>L.D.</given-names></name></person-group><article-title>Effects of cassia oil on serum and hepatic uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver</article-title><source>J. Ethnopharmacol.</source><volume>103</volume><fpage>357</fpage><lpage>365</lpage><year>2006</year><pub-id pub-id-type="pmid">16182482</pub-id></mixed-citation></ref></ref-list></back><floats-group><fig id="F1" position="float"><label>Fig. 1</label><caption><p>Effect of orange juice, hesperetin and allopurinol on serum uric acid. All values are expressed as mean ± SD (<italic>n</italic> = 6). Independent-sample <italic>t</italic> test was used for statistical significance assessment. <bold>*</bold> indicates <italic>p</italic>≤0.05, <bold>**</bold> indicates <italic>p</italic>≤0.01 and <bold>***</bold> indicates <italic>p</italic>≤0.001 vs hyperuricemic control group. The number above bars means the percent of uric acid reduction vs hyperuricemic control group.</p></caption><graphic xlink:href="jcbn09-15f01"></graphic></fig><fig id="F2" position="float"><label>Fig. 2</label><caption><p>Linear regression between serum uric acid levels and MDA concentration</p></caption><graphic xlink:href="jcbn09-15f02"></graphic></fig><table-wrap id="T1" position="float"><label>Table 1</label><caption><p>Effect of orange juice, hesperetin and allopurinol on serum TAC and MDA</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Treatment</th><th align="center" rowspan="1" colspan="1">TAC (µmol/L)</th><th align="center" rowspan="1" colspan="1">MDA (µmol/L)</th></tr></thead><tbody><tr><td colspan="3" align="left" rowspan="1"><bold>Normal animal</bold></td></tr><tr><td align="left" rowspan="1" colspan="1">Vehicle</td><td align="center" rowspan="1" colspan="1">275 ± 78.67*</td><td align="center" rowspan="1" colspan="1">3.41 ± 0.57</td></tr><tr><td colspan="3" align="left" rowspan="1"><bold>Hyperuricemic animal</bold></td></tr><tr><td align="left" rowspan="1" colspan="1">PO + vehicle</td><td align="center" rowspan="1" colspan="1">213 ± 65.92<sup>#</sup></td><td align="center" rowspan="1" colspan="1">5.45 ± 0.89<sup>###</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">PO + orange juice (5 ml/kg)</td><td align="center" rowspan="1" colspan="1">280 ± 30.16*</td><td align="center" rowspan="1" colspan="1">4.04 ± 0.86*</td></tr><tr><td align="left" rowspan="1" colspan="1">PO + hesperetin (5 mg/kg)</td><td align="center" rowspan="1" colspan="1">271 ± 52.31</td><td align="center" rowspan="1" colspan="1">4.95 ± 0.71<sup>##</sup></td></tr><tr><td align="left" rowspan="1" colspan="1">PO + allopurinol (5 mg/kg)</td><td align="center" rowspan="1" colspan="1">244 ± 57.27</td><td align="center" rowspan="1" colspan="1">5.00 ± 0.92<sup>##</sup></td></tr></tbody></table><table-wrap-foot><p>All values are expressed as mean ± SD (<italic>n</italic> = 6). Independent-sample <italic>t</italic> test was used for statistical significance assessment. * indicates <italic>p</italic>≤0.05 vs hyperuricemic control group, <sup>#</sup> indicates <italic>p</italic>≤0.05, <sup>##</sup> indicates <italic>p</italic>≤0.01 and <sup>###</sup> indicates <italic>p</italic>≤0.001 vs normal control group.</p></table-wrap-foot></table-wrap><table-wrap id="T2" position="float"><label>Table 2</label><caption><p>Effect of orange juice, hesperetin and allopurinol on hepatic XO and XDH activity</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Treatment</th><th colspan="2" align="center" rowspan="1">Activity (U/mg protein)<hr></hr></th><th colspan="2" align="center" rowspan="1">Inhibition %<hr></hr></th></tr><tr><th rowspan="1" colspan="1"></th><th align="center" rowspan="1" colspan="1">XO</th><th align="center" rowspan="1" colspan="1">XDH</th><th align="center" rowspan="1" colspan="1">XO</th><th align="center" rowspan="1" colspan="1">XDH</th></tr></thead><tbody><tr><td align="left" rowspan="1" colspan="1"><bold>Normal animal</bold></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">Vehicle</td><td align="center" rowspan="1" colspan="1">2.50 ± 0.63</td><td align="center" rowspan="1" colspan="1">3.80 ± 0.38</td><td align="center" rowspan="1" colspan="1">—</td><td align="center" rowspan="1" colspan="1">—</td></tr><tr><td align="left" rowspan="1" colspan="1"><bold>Hyperuricemic animal</bold></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td><td rowspan="1" colspan="1"></td></tr><tr><td align="left" rowspan="1" colspan="1">PO + vehicle</td><td align="center" rowspan="1" colspan="1">2.49 ± 0.52</td><td align="center" rowspan="1" colspan="1">3.82 ± 0.62</td><td align="center" rowspan="1" colspan="1">—</td><td align="center" rowspan="1" colspan="1">—</td></tr><tr><td align="left" rowspan="1" colspan="1">PO + orange juice (5 ml/kg)</td><td align="center" rowspan="1" colspan="1">1.88 ± 0.37*<sup>,#</sup></td><td align="center" rowspan="1" colspan="1">2.64 ± 0.20***<sup>,###</sup></td><td align="center" rowspan="1" colspan="1">24.49</td><td align="center" rowspan="1" colspan="1">30.89</td></tr><tr><td align="left" rowspan="1" colspan="1">PO + hesperetin (5 mg/kg)</td><td align="center" rowspan="1" colspan="1">1.90 ± 0.37*<sup>,#</sup></td><td align="center" rowspan="1" colspan="1">3.03 ± 0.29*<sup>,##</sup></td><td align="center" rowspan="1" colspan="1">23.69</td><td align="center" rowspan="1" colspan="1">20.68</td></tr><tr><td align="left" rowspan="1" colspan="1">PO + allopurinol (5 mg/kg)</td><td align="center" rowspan="1" colspan="1">1.05 ± 0.18***<sup>,###</sup></td><td align="center" rowspan="1" colspan="1">1.27 ± 0.33***<sup>,###</sup></td><td align="center" rowspan="1" colspan="1">57.83</td><td align="center" rowspan="1" colspan="1">66.75</td></tr></tbody></table><table-wrap-foot><p>All values are expressed as mean ± SD (<italic>n</italic> = 6). Independent-sample <italic>t</italic> test was used for statistical significance assessment. * indicates <italic>p</italic>≤0.05, and *** indicates <italic>p</italic>≤0.001 vs hyperuricemic control group, <sup>#</sup> indicates <italic>p</italic>≤0.05, <sup>##</sup> indicates <italic>p</italic>≤0.01 and <sup>###</sup> indicates <italic>p</italic>≤0.001 vs normal control group.</p></table-wrap-foot></table-wrap></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Bois/explor/OrangerV1/Data/Pmc/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001009 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd -nk 001009 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Bois
|area= OrangerV1
|flux= Pmc
|étape= Corpus
|type= RBID
|clé= PMC:2771249
|texte= Orange Juice and Hesperetin Supplementation to Hyperuricemic Rats Alter Oxidative Stress Markers and Xanthine Oxidoreductase Activity
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Pmc/Corpus/RBID.i -Sk "pubmed:19902018" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Pmc/Corpus/biblio.hfd \
| NlmPubMed2Wicri -a OrangerV1
| This area was generated with Dilib version V0.6.25. |  |