Effect of some Indole Derivatives on Xenobiotic Metabolism and Xenobiotic-induced Toxicity in Cultured Rat Liver Slices
Identifieur interne : 001950 ( Istex/Corpus ); précédent : 001949; suivant : 001951Effect of some Indole Derivatives on Xenobiotic Metabolism and Xenobiotic-induced Toxicity in Cultured Rat Liver Slices
Auteurs : A. B. Renwick ; H. Mistry ; P. T. Barton ; F. Mallet ; R. J. Price ; J. A. Beamand ; B. G. LakeSource :
- Food and Chemical Toxicology [ 0278-6915 ] ; 1999.
Abstract
In this study the effect of some indole derivatives on xenobiotic metabolizing enzymes and xenobiotic-induced toxicity has been examined in cultured precision-cut liver slices from male Sprague–Dawley rats. While treatment of rat liver slices for 72 hours with 2–200 μm of either indole-3-carbinol (I3C) or indole-3-acetonitrile (3-ICN) had little effect on cytochrome P-450 (CYP)-dependent enzyme activities, enzyme induction was observed after in vivo administration of I3C. The treatment of rat liver slices with 50 μm 3,3′-diindolylmethane (DIM; a dimer derived from I3C under acidic conditions) for 72 hours resulted in a marked induction of CYP-dependent enzyme activities. DIM appears to be a mixed inducer of CYP in rat liver slices having effects on CYP1A, CYP2B and CYP3A subfamily isoforms. Small increases in liver slice reduced glutathione levels and glutathione S-transferase activity were also observed after DIM treatment. While aflatoxin B1 and monocrotaline produced a concentration-dependent inhibition of protein synthesis in 72-hour-cultured rat liver slices, cytotoxicity was markedly reduced in liver slices cultured with 50 μm DIM. These results demonstrate that cultured rat liver slices may be employed to evaluate the effects of chemicals derived from cruciferous and other vegetables on CYP isoforms. In addition, liver slices can also be utilized to examine the ability of such chemicals to modulate xenobiotic-induced toxicity.
Url:
DOI: 10.1016/S0278-6915(99)00026-5
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Barton</name><affiliation><mods:affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</mods:affiliation></affiliation></author><author><name sortKey="Mallet, F" sort="Mallet, F" uniqKey="Mallet F" first="F." last="Mallet">F. Mallet</name><affiliation><mods:affiliation>ENS BANA, Universitéde Bourgogne, Campus Universitaire Montmuzard, 21000 Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Price, R J" sort="Price, R J" uniqKey="Price R" first="R. J." last="Price">R. J. Price</name><affiliation><mods:affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</mods:affiliation></affiliation></author><author><name sortKey="Beamand, J A" sort="Beamand, J A" uniqKey="Beamand J" first="J. A." last="Beamand">J. A. 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Renwick</name><affiliation><mods:affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</mods:affiliation></affiliation></author><author><name sortKey="Mistry, H" sort="Mistry, H" uniqKey="Mistry H" first="H." last="Mistry">H. Mistry</name><affiliation><mods:affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</mods:affiliation></affiliation></author><author><name sortKey="Barton, P T" sort="Barton, P T" uniqKey="Barton P" first="P. T." last="Barton">P. T. Barton</name><affiliation><mods:affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</mods:affiliation></affiliation></author><author><name sortKey="Mallet, F" sort="Mallet, F" uniqKey="Mallet F" first="F." last="Mallet">F. Mallet</name><affiliation><mods:affiliation>ENS BANA, Universitéde Bourgogne, Campus Universitaire Montmuzard, 21000 Dijon, France</mods:affiliation></affiliation></author><author><name sortKey="Price, R J" sort="Price, R J" uniqKey="Price R" first="R. J." last="Price">R. J. Price</name><affiliation><mods:affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</mods:affiliation></affiliation></author><author><name sortKey="Beamand, J A" sort="Beamand, J A" uniqKey="Beamand J" first="J. A." last="Beamand">J. A. Beamand</name><affiliation><mods:affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</mods:affiliation></affiliation></author><author><name sortKey="Lake, B G" sort="Lake, B G" uniqKey="Lake B" first="B. G." last="Lake">B. G. Lake</name><affiliation><mods:affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Food and Chemical Toxicology</title><title level="j" type="abbrev">FCT</title><idno type="ISSN">0278-6915</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999">1999</date><biblScope unit="volume">37</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="609">609</biblScope><biblScope unit="page" to="618">618</biblScope></imprint><idno type="ISSN">0278-6915</idno></series><idno type="istex">275E4CF8E30661F255DCC690CCEF8F521DCAD7AA</idno><idno type="DOI">10.1016/S0278-6915(99)00026-5</idno><idno type="PII">S0278-6915(99)00026-5</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0278-6915</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In this study the effect of some indole derivatives on xenobiotic metabolizing enzymes and xenobiotic-induced toxicity has been examined in cultured precision-cut liver slices from male Sprague–Dawley rats. While treatment of rat liver slices for 72 hours with 2–200 μm of either indole-3-carbinol (I3C) or indole-3-acetonitrile (3-ICN) had little effect on cytochrome P-450 (CYP)-dependent enzyme activities, enzyme induction was observed after in vivo administration of I3C. The treatment of rat liver slices with 50 μm 3,3′-diindolylmethane (DIM; a dimer derived from I3C under acidic conditions) for 72 hours resulted in a marked induction of CYP-dependent enzyme activities. DIM appears to be a mixed inducer of CYP in rat liver slices having effects on CYP1A, CYP2B and CYP3A subfamily isoforms. Small increases in liver slice reduced glutathione levels and glutathione S-transferase activity were also observed after DIM treatment. While aflatoxin B1 and monocrotaline produced a concentration-dependent inhibition of protein synthesis in 72-hour-cultured rat liver slices, cytotoxicity was markedly reduced in liver slices cultured with 50 μm DIM. These results demonstrate that cultured rat liver slices may be employed to evaluate the effects of chemicals derived from cruciferous and other vegetables on CYP isoforms. In addition, liver slices can also be utilized to examine the ability of such chemicals to modulate xenobiotic-induced toxicity.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>A.B. Renwick</name><affiliations><json:string>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</json:string></affiliations></json:item><json:item><name>H. Mistry</name><affiliations><json:string>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</json:string></affiliations></json:item><json:item><name>P.T. Barton</name><affiliations><json:string>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</json:string></affiliations></json:item><json:item><name>F. Mallet</name><affiliations><json:string>ENS BANA, Universitéde Bourgogne, Campus Universitaire Montmuzard, 21000 Dijon, France</json:string></affiliations></json:item><json:item><name>R.J. Price</name><affiliations><json:string>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</json:string></affiliations></json:item><json:item><name>J.A. Beamand</name><affiliations><json:string>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</json:string></affiliations></json:item><json:item><name>B.G. Lake</name><affiliations><json:string>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>cytochrome P-450</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>3,3′-diindolylmethane</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>enzyme induction in vitro</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>rat liver</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>precision-cut rat liver slices</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>AFB1=aflatoxin B1</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ARO=Aroclor 1254</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>CYP=cytochrome P-450</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>DIM=3,3′-diindolylmethane</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>DMSO=dimethyl sulfoxide</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>GSH=reduced glutathione</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>GSSG=oxidized glutathione</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>I3C=indole-3-carbinol</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>3-ICN=indole-3-acetonitrile</value></json:item></subject><language><json:string>eng</json:string></language><originalGenre><json:string>Full-length article</json:string></originalGenre><abstract>In this study the effect of some indole derivatives on xenobiotic metabolizing enzymes and xenobiotic-induced toxicity has been examined in cultured precision-cut liver slices from male Sprague–Dawley rats. While treatment of rat liver slices for 72 hours with 2–200 μm of either indole-3-carbinol (I3C) or indole-3-acetonitrile (3-ICN) had little effect on cytochrome P-450 (CYP)-dependent enzyme activities, enzyme induction was observed after in vivo administration of I3C. The treatment of rat liver slices with 50 μm 3,3′-diindolylmethane (DIM; a dimer derived from I3C under acidic conditions) for 72 hours resulted in a marked induction of CYP-dependent enzyme activities. DIM appears to be a mixed inducer of CYP in rat liver slices having effects on CYP1A, CYP2B and CYP3A subfamily isoforms. Small increases in liver slice reduced glutathione levels and glutathione S-transferase activity were also observed after DIM treatment. While aflatoxin B1 and monocrotaline produced a concentration-dependent inhibition of protein synthesis in 72-hour-cultured rat liver slices, cytotoxicity was markedly reduced in liver slices cultured with 50 μm DIM. These results demonstrate that cultured rat liver slices may be employed to evaluate the effects of chemicals derived from cruciferous and other vegetables on CYP isoforms. In addition, liver slices can also be utilized to examine the ability of such chemicals to modulate xenobiotic-induced toxicity.</abstract><qualityIndicators><score>7.532</score><pdfVersion>1.2</pdfVersion><pdfPageSize>595 x 792 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>14</keywordCount><abstractCharCount>1457</abstractCharCount><pdfWordCount>5148</pdfWordCount><pdfCharCount>31800</pdfCharCount><pdfPageCount>10</pdfPageCount><abstractWordCount>211</abstractWordCount></qualityIndicators><title>Effect of some Indole Derivatives on Xenobiotic Metabolism and Xenobiotic-induced Toxicity in Cultured Rat Liver Slices</title><pii><json:string>S0278-6915(99)00026-5</json:string></pii><refBibs><json:item><author><json:item><name>J.D. Adams, Jr</name></json:item><json:item><name>B.H. Lauterberg</name></json:item><json:item><name>J.R. Mitchell</name></json:item></author><host><volume>227</volume><pages><last>754</last><first>749</first></pages><author></author><title>Journal of Pharmacology and Experimental Therapeutics</title></host><title>Plasma glutathione and glutathione disulfide in the rat: regulation and response to oxidative stress</title></json:item><json:item><author><json:item><name>P.H. Bach</name></json:item><json:item><name>A.E.M. Vickers</name></json:item><json:item><name>R. Fisher</name></json:item><json:item><name>A. Baumann</name></json:item><json:item><name>E. Brittebo</name></json:item><json:item><name>D.J. Carlile</name></json:item><json:item><name>H.J. Koster</name></json:item><json:item><name>B.G. Lake</name></json:item><json:item><name>F. Salmon</name></json:item><json:item><name>T.W. Sawyer</name></json:item><json:item><name>G. Skibinski</name></json:item></author><host><volume>24</volume><pages><last>923</last><first>893</first></pages><author></author><title>ATLA</title></host><title>The use of tissue slices for pharmacotoxicology studies. The report and recommendations of ECVAM Workshop 20</title></json:item><json:item><author><json:item><name>J.A. Beamand</name></json:item><json:item><name>R.J. Price</name></json:item><json:item><name>M.E. Cunninghame</name></json:item><json:item><name>B.G. Lake</name></json:item></author><host><volume>31</volume><pages><last>147</last><first>137</first></pages><author></author><title>Food and Chemical Toxicology</title></host><title>Culture of precision-cut liver slices : effect of some peroxisome proliferators</title></json:item><json:item><author><json:item><name>L.F. Bjeldanes</name></json:item><json:item><name>J-Y. Kim</name></json:item><json:item><name>K.R. Grose</name></json:item><json:item><name>J.C. Bartholomew</name></json:item><json:item><name>C.A. Bradfield</name></json:item></author><host><volume>88</volume><pages><last>9547</last><first>9543</first></pages><author></author><title>Proceedings of the National Academy of Sciences of the U.S.A.</title></host><title>Aromatic hydrocarbon responsiveness-receptor agonists generated from indole-3-carbinol in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin</title></json:item><json:item><author><json:item><name>M.D. Burke</name></json:item><json:item><name>S. Thompson</name></json:item><json:item><name>C.R. Elcombe</name></json:item><json:item><name>J. Halpert</name></json:item><json:item><name>T. Haaparanta</name></json:item><json:item><name>R.T. Mayer</name></json:item></author><host><volume>34</volume><pages><last>3345</last><first>3337</first></pages><author></author><title>Biochemical Pharmacology</title></host><title>Ethoxy-, pentoxy- and benzyloxyphenoxazones and homologues : a series of substrates to distinguish between different induced cytochromes P-450</title></json:item><json:item><author><json:item><name>I. Chen</name></json:item><json:item><name>S. Safe</name></json:item><json:item><name>L. Bjeldanes</name></json:item></author><host><volume>51</volume><pages><last>1076</last><first>1069</first></pages><author></author><title>Biochemical Pharmacology</title></host><title>Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells</title></json:item><json:item><author><json:item><name>A.H. Conney</name></json:item></author><host><volume>39</volume><pages><last>2518</last><first>2493</first></pages><author></author><title>Life Sciences</title></host><title>Induction of microsomal cytochrome P-450 enzymes : the first Bernard B. Brodie lecture at Pennyslvania State University</title></json:item><json:item><author><json:item><name>C.A. de Kruif</name></json:item><json:item><name>J.W. Marsman</name></json:item><json:item><name>J.C. Venekamp</name></json:item><json:item><name>H.E. Falke</name></json:item><json:item><name>J. Noordhoek</name></json:item><json:item><name>B.J. Blaauboer</name></json:item><json:item><name>H.M. Wortelboer</name></json:item></author><host><volume>80</volume><pages><last>315</last><first>303</first></pages><author></author><title>Chemico–Biological Interactions</title></host><title>Structure elucidation of acid reaction products of indole-3–carbinol: detection in vivo and enzyme induction in vitro</title></json:item><json:item><author><json:item><name>A.T. Drahushuk</name></json:item><json:item><name>B.P. McGarrigle</name></json:item><json:item><name>H-L. Tai</name></json:item><json:item><name>S. Kitareewan</name></json:item><json:item><name>J.A. Goldstein</name></json:item><json:item><name>J.R. Olson</name></json:item></author><host><volume>140</volume><pages><last>403</last><first>393</first></pages><author></author><title>Toxicology and Applied Pharmacology</title></host><title>Validation of precision-cut liver slices in dynamic organ culture as an in vitro model for studying CYP1A1 and CYP1A2 induction</title></json:item><json:item><author><json:item><name>S.R. Dueker</name></json:item><json:item><name>M.W. Lamé</name></json:item><json:item><name>D. Morin</name></json:item><json:item><name>D.W. Wilson</name></json:item><json:item><name>H.J. Segall</name></json:item></author><host><volume>20</volume><pages><last>280</last><first>275</first></pages><author></author><title>Drug Metabolism and Disposition</title></host><title>Guinea pig and rat hepatic microsomal metabolism of monocrotaline</title></json:item><json:item><author><json:item><name>D.L. Eaton</name></json:item><json:item><name>E.P. Gallagher</name></json:item></author><host><volume>34</volume><pages><last>172</last><first>135</first></pages><author></author><title>Annual Review of Pharmacology and Toxicology</title></host><title>Mechanisms of aflatoxin carcinogenesis</title></json:item><json:item><author><json:item><name>M.S. Gokhale</name></json:item><json:item><name>T.E. Bunton</name></json:item><json:item><name>J. Zurlo</name></json:item><json:item><name>J.D. Yager</name></json:item></author><host><volume>27</volume><pages><last>355</last><first>341</first></pages><author></author><title>Xenobiotica</title></host><title>Cytochrome P450 isoenzyme activities in cultured rat and mouse liver slices</title></json:item><json:item><author><json:item><name>D. Guo</name></json:item><json:item><name>H.A.J. Schut</name></json:item><json:item><name>C.D. Davis</name></json:item><json:item><name>E.G. Snyderwine</name></json:item><json:item><name>G.S. Bailey</name></json:item><json:item><name>R.H. Dashwood</name></json:item></author><host><volume>16</volume><pages><last>2937</last><first>2931</first></pages><author></author><title>Carcinogenesis</title></host><title>Protection by chlorophyllin and indole-3-carbinol against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced DNA adducts and colonic aberrant crypts in the F344 rat</title></json:item><json:item><author><json:item><name>W.H. Habig</name></json:item><json:item><name>M.J. Pabst</name></json:item><json:item><name>W.B. Jakoby</name></json:item></author><host><volume>249</volume><pages><last>7139</last><first>7130</first></pages><author></author><title>Journal of Biological Chemistry</title></host><title>Glutathione S-transferases. The first step in mercapturic acid formation</title></json:item><json:item><host><author></author></host></json:item><json:item><author><json:item><name>S. Imaoka</name></json:item><json:item><name>S. Ikemoto</name></json:item><json:item><name>T. Shimada</name></json:item><json:item><name>Y. Funae</name></json:item></author><host><volume>269</volume><pages><last>236</last><first>231</first></pages><author></author><title>Mutation Research</title></host><title>Mutagenic activation of aflatoxin B1 by pulmonary, renal and hepatic cytochrome P450 s from rats</title></json:item><json:item><author><json:item><name>A.C. Japenga</name></json:item><json:item><name>S. Davies</name></json:item><json:item><name>R.J. Price</name></json:item><json:item><name>B.G. Lake</name></json:item></author><host><volume>23</volume><pages><last>179</last><first>169</first></pages><author></author><title>Xenobiotica</title></host><title>Effect of treatment with pyrazine and some derivatives on cytochrome P450 and some enzyme activities in rat liver</title></json:item><json:item><author><json:item><name>M.A. Kall</name></json:item><json:item><name>O. Vang</name></json:item><json:item><name>J. Clausen</name></json:item></author><host><volume>17</volume><pages><last>799</last><first>793</first></pages><author></author><title>Carcinogenesis</title></host><title>Effects of dietary broccoli on human in vivo drug metabolizing enzymes : evaluation of caffeine, oestrone and chlorzoxazone metabolism</title></json:item><json:item><host><author></author></host></json:item><json:item><author><json:item><name>B.G. Lake</name></json:item><json:item><name>J.A. Beamand</name></json:item><json:item><name>A.C. Japenga</name></json:item><json:item><name>A. Renwick</name></json:item><json:item><name>S. Davies</name></json:item><json:item><name>R.J. Price</name></json:item></author><host><volume>31</volume><pages><last>386</last><first>377</first></pages><author></author><title>Food and Chemical Toxicology</title></host><title>Induction of cytochrome P-450-dependent enzyme activities in cultured rat liver slices</title></json:item><json:item><author><json:item><name>B.G. Lake</name></json:item><json:item><name>C. Charzat</name></json:item><json:item><name>J.M. Tredger</name></json:item><json:item><name>A.B. Renwick</name></json:item><json:item><name>J.A. Beamand</name></json:item><json:item><name>R.J. Price</name></json:item></author><host><volume>26</volume><pages><last>306</last><first>297</first></pages><author></author><title>Xenobiotica</title></host><title>Induction of cytochrome P450 isoenzymes in cultured precision-cut rat and human liver slices</title></json:item><json:item><author><json:item><name>B.G. Lake</name></json:item><json:item><name>J.M. Tredger</name></json:item><json:item><name>A.B. Renwick</name></json:item><json:item><name>P.T. Barton</name></json:item><json:item><name>R.J. Price</name></json:item></author><host><volume>28</volume><pages><last>811</last><first>803</first></pages><author></author><title>Xenobiotica</title></host><title>3,3′-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices</title></json:item><json:item><author><json:item><name>E.L. LeCluyse</name></json:item><json:item><name>P.L. Bullock</name></json:item><json:item><name>A. Parkinson</name></json:item></author><host><volume>22</volume><pages><last>186</last><first>133</first></pages><author></author><title>Advanced Drug Delivery Reviews</title></host><title>Strategies for restoration and maintenance of normal hepatic structure and function in long-term cultures of rat hepatocytes</title></json:item><json:item><author><json:item><name>O.H. Lowry</name></json:item><json:item><name>N.J. Rosebrough</name></json:item><json:item><name>A.L. Farr</name></json:item><json:item><name>R.J. Randall</name></json:item></author><host><volume>193</volume><pages><last>275</last><first>265</first></pages><author></author><title>Journal of Biological Chemistry</title></host><title>Protein measurement with the Folin phenol reagent</title></json:item><json:item><author><json:item><name>R.E. McDanell</name></json:item><json:item><name>L.A. Henderson</name></json:item><json:item><name>K. Russell</name></json:item><json:item><name>A.E.M. McLean</name></json:item></author><host><volume>11</volume><pages><last>172</last><first>167</first></pages><author></author><title>Human and Experimental Toxicology</title></host><title>The effect of brassica vegetable consumption on caffeine metabolism in humans</title></json:item><json:item><author><json:item><name>R. McDanell</name></json:item><json:item><name>A.E.M. McLean</name></json:item><json:item><name>A.B. Hanley</name></json:item><json:item><name>R.K. Heaney</name></json:item><json:item><name>G.R. Fenwick</name></json:item></author><host><volume>25</volume><pages><last>368</last><first>363</first></pages><author></author><title>Food and Chemical Toxicology</title></host><title>Differential induction of mixed-function oxidase (MFO) activity in rat liver and intestine by diets containing processed cabbage: correlation with cabbage levels of glucosinolates and glucosinolate hydrolysis products</title></json:item><json:item><author><json:item><name>R. McDanell</name></json:item><json:item><name>A.E.M. McLean</name></json:item><json:item><name>A.B. Hanley</name></json:item><json:item><name>R.K. Heaney</name></json:item><json:item><name>G.R. Fenwick</name></json:item></author><host><volume>26</volume><pages><last>70</last><first>59</first></pages><author></author><title>Food and Chemical Toxicology</title></host><title>Chemical and biological properties of indole glucosinolates (glucobrassicins): a review</title></json:item><json:item><author><json:item><name>D. Müller</name></json:item><json:item><name>R. Glöckner</name></json:item><json:item><name>M. Rost</name></json:item></author><host><volume>48</volume><pages><last>438</last><first>433</first></pages><author></author><title>Experimental Toxicology and Pathology</title></host><title>Monooxygenation, cytochrome P4501A1 and P4501A1–mRNA in rat liver slices exposed to beta-naphthoflavone and dexamethasone in vitro</title></json:item><json:item><author><json:item><name>D.R. Nelson</name></json:item><json:item><name>L. Koymans</name></json:item><json:item><name>T. Kamataki</name></json:item><json:item><name>J.J. Stegeman</name></json:item><json:item><name>R. Feyereisen</name></json:item><json:item><name>D.J. Waxman</name></json:item><json:item><name>M.R. Waterman</name></json:item><json:item><name>O. Gotoh</name></json:item><json:item><name>M.J. Coon</name></json:item><json:item><name>R.W. Estabrook</name></json:item><json:item><name>I.C. Gunsalus</name></json:item><json:item><name>D.W. Nebert</name></json:item></author><host><volume>6</volume><pages><last>42</last><first>1</first></pages><author></author><title>Pharmacogenetics</title></host><title>P450 superfamily : update on new sequences, gene mapping, accession numbers and nomenclature</title></json:item><json:item><author><json:item><name>P.V. Nerurkar</name></json:item><json:item><name>S.S. Park</name></json:item><json:item><name>P.E. Thomas</name></json:item><json:item><name>R.W. Nims</name></json:item><json:item><name>R.A. Lubet</name></json:item></author><host><volume>46</volume><pages><last>943</last><first>933</first></pages><author></author><title>Biochemical Pharmacology</title></host><title>Methoxyresorufin and benzyloxyresorufin : substrates preferentially metabolized by cytochromes P4501A2 and 2B, respectively, in the rat and mouse</title></json:item><json:item><author><json:item><name>A.B. Okey</name></json:item></author><host><volume>45</volume><pages><last>298</last><first>241</first></pages><author></author><title>Pharmacology and Therapeutics</title></host><title>Enzyme induction in the cytochrome P-450 system</title></json:item><json:item><author><json:item><name>E.J. Pantuck</name></json:item><json:item><name>C.B. Pantuck</name></json:item><json:item><name>K.E. Anderson</name></json:item><json:item><name>L.W. Wattenberg</name></json:item><json:item><name>A.H. Conney</name></json:item><json:item><name>A. Kappas</name></json:item></author><host><volume>35</volume><pages><last>169</last><first>161</first></pages><author></author><title>Clinical Pharmacology and Therapeutics</title></host><title>Effect of Brussels sprouts and cabbage on drug conjugation</title></json:item><json:item><author><json:item><name>E.J. Pantuck</name></json:item><json:item><name>C.B. Pantuck</name></json:item><json:item><name>W.A. Garland</name></json:item><json:item><name>B.H. Min</name></json:item><json:item><name>L.W. Wattenberg</name></json:item><json:item><name>K.E. Anderson</name></json:item><json:item><name>A. Kappas</name></json:item><json:item><name>A.H. Conney</name></json:item></author><host><volume>25</volume><pages><last>95</last><first>88</first></pages><author></author><title>Clinical Pharmacology and Therapeutics</title></host><title>Stimulatory effects of Brussels sprouts and cabbage on human drug metabolism</title></json:item><json:item><host><author></author></host></json:item><json:item><author><json:item><name>A.R. Parrish</name></json:item><json:item><name>A.J. Gandolfi</name></json:item><json:item><name>K. Brendel</name></json:item></author><host><volume>57</volume><pages><last>1901</last><first>1887</first></pages><author></author><title>Life Sciences</title></host><title>Precision-cut tissue slices : applications in pharmacology and toxicology</title></json:item><json:item><author><json:item><name>T. Prestera</name></json:item><json:item><name>W.D. Holtzclaw</name></json:item><json:item><name>Y. Zhang</name></json:item><json:item><name>P. Talalay</name></json:item></author><host><volume>90</volume><pages><last>2969</last><first>2965</first></pages><author></author><title>Proceedings of the National Academy of Sciences of the U.S.A.</title></host><title>Chemical and molecular regulation of enzymes that detoxify carcinogens</title></json:item><json:item><author><json:item><name>R.J. Price</name></json:item><json:item><name>H. Mistry</name></json:item><json:item><name>P.T. Wield</name></json:item><json:item><name>A.B. Renwick</name></json:item><json:item><name>J.A. Beamand</name></json:item><json:item><name>B.G. Lake</name></json:item></author><host><volume>71</volume><pages><last>111</last><first>107</first></pages><author></author><title>Archives of Toxicology</title></host><title>Comparison of the toxicity of allyl alcohol, coumarin and menadione in precision-cut rat, guinea-pig, Cynomolgus monkey and human liver slices</title></json:item><json:item><author><json:item><name>R.J. Price</name></json:item><json:item><name>A.B. Renwick</name></json:item><json:item><name>P.T. Barton</name></json:item><json:item><name>J.B. Houston</name></json:item><json:item><name>B.G. Lake</name></json:item></author><host><volume>26</volume><pages><last>548</last><first>541</first></pages><author></author><title>ATLA</title></host><title>Influence of slice thickness and culture conditions on the metabolism of 7-ethoxycoumarin in precision-cut rat liver slices</title></json:item><json:item><author><json:item><name>R. Staack</name></json:item><json:item><name>S. Kingston</name></json:item><json:item><name>M.A. Wallig</name></json:item><json:item><name>E.H. Jeffery</name></json:item></author><host><volume>149</volume><pages><last>23</last><first>17</first></pages><author></author><title>Toxicology and Applied Pharmacology</title></host><title>A comparison of the individual and collective effects of four glucosinolate breakdown products from Brussels sprouts on induction of detoxification enzymes</title></json:item><json:item><author><json:item><name>G.S. Stoewsand</name></json:item></author><host><volume>33</volume><pages><last>543</last><first>537</first></pages><author></author><title>Food and Chemical Toxicology</title></host><title>Bioactive organosulfur phytochemicals in Brassica oleracea vegetables—a review</title></json:item><json:item><author><json:item><name>O. Vang</name></json:item><json:item><name>H. Jensen</name></json:item><json:item><name>H. Autrup</name></json:item></author><host><volume>78</volume><pages><last>96</last><first>85</first></pages><author></author><title>Chemico–Biological Interactions</title></host><title>Induction of cytochrome P-450IA1, IA2, IIB1, IIB2 and IIE1 by broccoli in rat liver and colon</title></json:item><json:item><author><json:item><name>D.T.H. Verhoeven</name></json:item><json:item><name>H. Verhagen</name></json:item><json:item><name>R.A. Goldbohm</name></json:item><json:item><name>P.A. van den Brandt</name></json:item><json:item><name>G. van Poppel</name></json:item></author><host><volume>103</volume><pages><last>129</last><first>79</first></pages><author></author><title>Chemico–Biological Interactions</title></host><title>A review of mechanisms underlying anticarcinogenicity by brassica vegetables</title></json:item><json:item><author><json:item><name>H.M. Wortelboer</name></json:item><json:item><name>C.A. de Kruif</name></json:item><json:item><name>A.A.J. van Iersel</name></json:item><json:item><name>H.E. Falke</name></json:item><json:item><name>J. Noordhoek</name></json:item><json:item><name>B.J. Blaauboer</name></json:item></author><host><volume>43</volume><pages><last>1447</last><first>1439</first></pages><author></author><title>Biochemical Pharmacology</title></host><title>Acid reaction products of indole-3-carbinol and their effects on cytochrome P450 and phase II enzymes in rat and monkey hepatocytes</title></json:item><json:item><author><json:item><name>H.M. Wortelboer</name></json:item><json:item><name>C.A. de Kruif</name></json:item><json:item><name>A.A.J. van Iersel</name></json:item><json:item><name>J. Noordhoek</name></json:item><json:item><name>B.J. Blaauboer</name></json:item><json:item><name>P.J. van Bladeren</name></json:item><json:item><name>H.E. Falke</name></json:item></author><host><volume>30</volume><pages><last>27</last><first>17</first></pages><author></author><title>Food and Chemical Toxicology</title></host><title>Effects of cooked Brussels sprouts on cytochrome P-450 profile and phase II enzymes in liver and small intestinal mucosa of the rat</title></json:item><json:item><author><json:item><name>H.M. Wortelboer</name></json:item><json:item><name>E.C.M. van der Linden</name></json:item><json:item><name>C.A. de Kruif</name></json:item><json:item><name>J. Noordhoek</name></json:item><json:item><name>B.J. Blaauboer</name></json:item><json:item><name>P.J. van Bladeren</name></json:item><json:item><name>H.E. Falke</name></json:item></author><host><volume>30</volume><pages><last>599</last><first>589</first></pages><author></author><title>Food and Chemical Toxicology</title></host><title>Effects of indole-3-carbinol on biotransformation enzymes in the rat: in vivo changes in liver and small intestinal mucosa in comparison with primary hepatocyte cultures</title></json:item><json:item><author><json:item><name>M.C. Wright</name></json:item><json:item><name>A.J. Paine</name></json:item></author><host><volume>43</volume><pages><last>243</last><first>237</first></pages><author></author><title>Biochemical Pharmacology</title></host><title>Evidence that the loss of rat liver cytochrome P450 in vitro is not solely associated with the use of collagenase, the loss of cell–cell contacts and/or the absence of an extracellular matrix</title></json:item><json:item><author><json:item><name>Y. Zhang</name></json:item><json:item><name>P. Talalay</name></json:item><json:item><name>C-G. Cho</name></json:item><json:item><name>G.H. Posner</name></json:item></author><host><volume>89</volume><pages><last>2403</last><first>2399</first></pages><author></author><title>Proceedings of the National Academy of Sciences of the U.S.A.</title></host><title>A major inducer of anticarcinogenic protective enzymes from broccoli isolation and elucidation of structure</title></json:item><json:item><host><author></author></host></json:item></refBibs><genre><json:string>research-article</json:string></genre><host><volume>37</volume><pii><json:string>S0278-6915(00)X0048-8</json:string></pii><pages><last>618</last><first>609</first></pages><issn><json:string>0278-6915</json:string></issn><issue>6</issue><genre><json:string>journal</json:string></genre><language><json:string>unknown</json:string></language><title>Food and Chemical Toxicology</title><publicationDate>1999</publicationDate></host><categories><wos><json:string>science</json:string><json:string>toxicology</json:string><json:string>food science & technology</json:string></wos><scienceMetrix><json:string>applied sciences</json:string><json:string>agriculture, fisheries & forestry</json:string><json:string>food science</json:string></scienceMetrix></categories><publicationDate>1999</publicationDate><copyrightDate>1999</copyrightDate><doi><json:string>10.1016/S0278-6915(99)00026-5</json:string></doi><id>275E4CF8E30661F255DCC690CCEF8F521DCAD7AA</id><score>0.11690372</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/275E4CF8E30661F255DCC690CCEF8F521DCAD7AA/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/275E4CF8E30661F255DCC690CCEF8F521DCAD7AA/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/275E4CF8E30661F255DCC690CCEF8F521DCAD7AA/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a">Effect of some Indole Derivatives on Xenobiotic Metabolism and Xenobiotic-induced Toxicity in Cultured Rat Liver Slices</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>ELSEVIER</p></availability><date>1999</date></publicationStmt><notesStmt><note type="content">Section title: Research Section</note><note type="content">Fig. 1: Structures of indole derivatives studied.</note><note type="content">Plate. 1: Immunoblots of rat liver microsomes incubated with anti-CYP1A1 (A), anti-CYP1A2 (B) and anti-CYP2B1/2 (C). Microsomal fractions (5μg protein per lane) were prepared from control (corn oil treated; lanes 1 and 2) rats and from rats treated with 25 (lanes 3 and 4) and 100 (lanes 5 and 6) mg/kg/day I3C by oral gavage for 3 days.</note><note type="content">Fig. 2: Effect of I3C, 3-ICN and ARO on 7-ethoxyresorufin O-deethylase in cultured rat liver slices. Liver slices were cultured with 0–200 μm I3C, 0–200 μm3-ICN and 2μg ARO/ml for 72hr. Results are expressed as means±SEM of three experiments. Values significantly different from control (DMSO only treated) cultures are: ∗∗∗P<0.001.</note><note type="content">Fig. 3: Effect of I3C, 3-ICN and ARO on 7-benzoxyresorufin O-debenzylase in cultured rat liver slices. Liver slices were cultured with 0–200 μm I3C, 0–200 μm 3-ICN and 2μg ARO /ml for 72hr. Results are expressed as means±SEM of three experiments. Values significantly different from control (DMSO only treated) cultures are: ∗P<0.05; ∗∗∗P<0.001.</note><note type="content">Fig. 4: Effect of 2–200 μm DIM on 7-ethoxyresorufin O-deethylase activity in 72-hr cultured rat liver slices. Results are expressed as means of two experiments. Mean 7-ethoxyresorufin O-deethylase activity in control (DMSO only treated) liver slices was 2.80 pmol/min/mg protein.</note><note type="content">Plate. 2: Immunoblots of 72-hr cultured rat liver slice microsomal fractions incubated with anti-CYP1A2 (A) and anti-CYP3A (B). Microsomal fractions (15μg protein per lane) were prepared from pooled control (DMSO only treated; lane 1), 50 μm I3C (lane 2), 50 μm DIM (lane 3) and 2μg ARO/ml (lane 4) treated liver slices.</note><note type="content">Fig. 5: Effect of DIM on AFB1- and monocrotaline-induced cytotoxicity in cultured rat liver slices. Liver slices were cultured for 72hr with 0 and 50 μm DIM. The medium was then changed to medium containing l-[1-14C]leucine and either no toxin (control), or 5 and 20 μm AFB1, or 0.5 and 1mm monocrotaline and the slices cultured for a further 4hr. Results are expressed as means±SEM of five experiments. Values significantly different from the appropriate control are: ∗P<0.05; ∗∗P<0.01. Rates of protein synthesis in 0 and 50 μm DIM treated liver slices cultured without any toxin (control) were not significantly different (P>0.05).</note><note type="content">Table 1: Effect of I3C on relative liver weight and some parameters of hepatic xenobiotic metabolism in the rat</note><note type="content">Table 2: Effect of DIM on levels of protein, CYP isoform activities, glutathione and glutathione S-transferase in 72hr cultured rat liver slices</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Effect of some Indole Derivatives on Xenobiotic Metabolism and Xenobiotic-induced Toxicity in Cultured Rat Liver Slices</title><author xml:id="author-1"><persName><forename type="first">A.B.</forename><surname>Renwick</surname></persName><affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</affiliation></author><author xml:id="author-2"><persName><forename type="first">H.</forename><surname>Mistry</surname></persName><affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</affiliation></author><author xml:id="author-3"><persName><forename type="first">P.T.</forename><surname>Barton</surname></persName><affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</affiliation></author><author xml:id="author-4"><persName><forename type="first">F.</forename><surname>Mallet</surname></persName><affiliation>ENS BANA, Universitéde Bourgogne, Campus Universitaire Montmuzard, 21000 Dijon, France</affiliation></author><author xml:id="author-5"><persName><forename type="first">R.J.</forename><surname>Price</surname></persName><affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</affiliation></author><author xml:id="author-6"><persName><forename type="first">J.A.</forename><surname>Beamand</surname></persName><affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</affiliation></author><author xml:id="author-7"><persName><forename type="first">B.G.</forename><surname>Lake</surname></persName><note type="correspondence"><p>Corresponding author</p></note><affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</affiliation></author></analytic><monogr><title level="j">Food and Chemical Toxicology</title><title level="j" type="abbrev">FCT</title><idno type="pISSN">0278-6915</idno><idno type="PII">S0278-6915(00)X0048-8</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1999"></date><biblScope unit="volume">37</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="609">609</biblScope><biblScope unit="page" to="618">618</biblScope></imprint></monogr><idno type="istex">275E4CF8E30661F255DCC690CCEF8F521DCAD7AA</idno><idno type="DOI">10.1016/S0278-6915(99)00026-5</idno><idno type="PII">S0278-6915(99)00026-5</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1999</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>In this study the effect of some indole derivatives on xenobiotic metabolizing enzymes and xenobiotic-induced toxicity has been examined in cultured precision-cut liver slices from male Sprague–Dawley rats. While treatment of rat liver slices for 72 hours with 2–200 μm of either indole-3-carbinol (I3C) or indole-3-acetonitrile (3-ICN) had little effect on cytochrome P-450 (CYP)-dependent enzyme activities, enzyme induction was observed after in vivo administration of I3C. The treatment of rat liver slices with 50 μm 3,3′-diindolylmethane (DIM; a dimer derived from I3C under acidic conditions) for 72 hours resulted in a marked induction of CYP-dependent enzyme activities. DIM appears to be a mixed inducer of CYP in rat liver slices having effects on CYP1A, CYP2B and CYP3A subfamily isoforms. Small increases in liver slice reduced glutathione levels and glutathione S-transferase activity were also observed after DIM treatment. While aflatoxin B1 and monocrotaline produced a concentration-dependent inhibition of protein synthesis in 72-hour-cultured rat liver slices, cytotoxicity was markedly reduced in liver slices cultured with 50 μm DIM. These results demonstrate that cultured rat liver slices may be employed to evaluate the effects of chemicals derived from cruciferous and other vegetables on CYP isoforms. In addition, liver slices can also be utilized to examine the ability of such chemicals to modulate xenobiotic-induced toxicity.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>cytochrome P-450</term></item><item><term>3,3′-diindolylmethane</term></item><item><term>enzyme induction in vitro</term></item><item><term>rat liver</term></item><item><term>precision-cut rat liver slices</term></item></list></keywords></textClass><textClass><keywords scheme="keyword"><list><head>Abbreviations</head><item><term>AFB1=aflatoxin B1</term></item><item><term>ARO=Aroclor 1254</term></item><item><term>CYP=cytochrome P-450</term></item><item><term>DIM=3,3′-diindolylmethane</term></item><item><term>DMSO=dimethyl sulfoxide</term></item><item><term>GSH=reduced glutathione</term></item><item><term>GSSG=oxidized glutathione</term></item><item><term>I3C=indole-3-carbinol</term></item><item><term>3-ICN=indole-3-acetonitrile</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1999">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/275E4CF8E30661F255DCC690CCEF8F521DCAD7AA/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: ce:floats; body; tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"><istex:entity SYSTEM="gr1" NDATA="IMAGE" name="gr1"></istex:entity><istex:entity SYSTEM="gr2" NDATA="IMAGE" name="gr2"></istex:entity><istex:entity SYSTEM="gr3" NDATA="IMAGE" name="gr3"></istex:entity><istex:entity SYSTEM="gr4" NDATA="IMAGE" name="gr4"></istex:entity><istex:entity SYSTEM="gr5" NDATA="IMAGE" name="gr5"></istex:entity></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>FCT</jid><aid>758</aid><ce:pii>S0278-6915(99)00026-5</ce:pii><ce:doi>10.1016/S0278-6915(99)00026-5</ce:doi><ce:copyright year="1999" type="unknown"></ce:copyright></item-info><head><ce:dochead><ce:textfn>Research Section</ce:textfn></ce:dochead><ce:title>Effect of some Indole Derivatives on Xenobiotic Metabolism and Xenobiotic-induced Toxicity in Cultured Rat Liver Slices</ce:title><ce:author-group><ce:author><ce:given-name>A.B.</ce:given-name><ce:surname>Renwick</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>H.</ce:given-name><ce:surname>Mistry</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>P.T.</ce:given-name><ce:surname>Barton</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>F.</ce:given-name><ce:surname>Mallet</ce:surname><ce:cross-ref refid="AFF2">b</ce:cross-ref></ce:author><ce:author><ce:given-name>R.J.</ce:given-name><ce:surname>Price</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>J.A.</ce:given-name><ce:surname>Beamand</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref></ce:author><ce:author><ce:given-name>B.G.</ce:given-name><ce:surname>Lake</ce:surname><ce:cross-ref refid="AFF1">a</ce:cross-ref><ce:cross-ref refid="CORR1">*</ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>ENS BANA, Universitéde Bourgogne, Campus Universitaire Montmuzard, 21000 Dijon, France</ce:textfn></ce:affiliation><ce:correspondence id="CORR1"><ce:label>*</ce:label><ce:text>Corresponding author</ce:text></ce:correspondence></ce:author-group><ce:date-accepted day="7" month="10" year="1998"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>In this study the effect of some indole derivatives on xenobiotic metabolizing enzymes and xenobiotic-induced toxicity has been examined in cultured precision-cut liver slices from male Sprague–Dawley rats. While treatment of rat liver slices for 72 hours with 2–200 <ce:italic>μ</ce:italic><ce:small-caps>m</ce:small-caps> of either indole-3-carbinol (I3C) or indole-3-acetonitrile (3-ICN) had little effect on cytochrome P-450 (CYP)-dependent enzyme activities, enzyme induction was observed after <ce:italic>in vivo</ce:italic> administration of I3C. The treatment of rat liver slices with 50 <ce:italic>μ</ce:italic><ce:small-caps>m</ce:small-caps> 3,3′-diindolylmethane (DIM; a dimer derived from I3C under acidic conditions) for 72 hours resulted in a marked induction of CYP-dependent enzyme activities. DIM appears to be a mixed inducer of CYP in rat liver slices having effects on CYP1A, CYP2B and CYP3A subfamily isoforms. Small increases in liver slice reduced glutathione levels and glutathione <ce:italic>S</ce:italic>-transferase activity were also observed after DIM treatment. While aflatoxin B<ce:inf>1</ce:inf> and monocrotaline produced a concentration-dependent inhibition of protein synthesis in 72-hour-cultured rat liver slices, cytotoxicity was markedly reduced in liver slices cultured with 50 <ce:italic>μ</ce:italic><ce:small-caps>m</ce:small-caps> DIM. These results demonstrate that cultured rat liver slices may be employed to evaluate the effects of chemicals derived from cruciferous and other vegetables on CYP isoforms. In addition, liver slices can also be utilized to examine the ability of such chemicals to modulate xenobiotic-induced toxicity.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords class="keyword"><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>cytochrome P-450</ce:text></ce:keyword><ce:keyword><ce:text>3,3′-diindolylmethane</ce:text></ce:keyword><ce:keyword><ce:text>enzyme induction <ce:italic>in vitro</ce:italic></ce:text></ce:keyword><ce:keyword><ce:text>rat liver</ce:text></ce:keyword><ce:keyword><ce:text>precision-cut rat liver slices</ce:text></ce:keyword></ce:keywords><ce:keywords class="abr"><ce:section-title>Abbreviations</ce:section-title><ce:keyword><ce:text>AFB<ce:inf>1</ce:inf>=aflatoxin B<ce:inf>1</ce:inf></ce:text></ce:keyword><ce:keyword><ce:text>ARO=Aroclor 1254</ce:text></ce:keyword><ce:keyword><ce:text>CYP=cytochrome P-450</ce:text></ce:keyword><ce:keyword><ce:text>DIM=3,3′-diindolylmethane</ce:text></ce:keyword><ce:keyword><ce:text>DMSO=dimethyl sulfoxide</ce:text></ce:keyword><ce:keyword><ce:text>GSH=reduced glutathione</ce:text></ce:keyword><ce:keyword><ce:text>GSSG=oxidized glutathione</ce:text></ce:keyword><ce:keyword><ce:text>I3C=indole-3-carbinol</ce:text></ce:keyword><ce:keyword><ce:text>3-ICN=indole-3-acetonitrile</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Effect of some Indole Derivatives on Xenobiotic Metabolism and Xenobiotic-induced Toxicity in Cultured Rat Liver Slices</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Effect of some Indole Derivatives on Xenobiotic Metabolism and Xenobiotic-induced Toxicity in Cultured Rat Liver Slices</title></titleInfo><name type="personal"><namePart type="given">A.B.</namePart><namePart type="family">Renwick</namePart><affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">H.</namePart><namePart type="family">Mistry</namePart><affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">P.T.</namePart><namePart type="family">Barton</namePart><affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">F.</namePart><namePart type="family">Mallet</namePart><affiliation>ENS BANA, Universitéde Bourgogne, Campus Universitaire Montmuzard, 21000 Dijon, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">R.J.</namePart><namePart type="family">Price</namePart><affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J.A.</namePart><namePart type="family">Beamand</namePart><affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">B.G.</namePart><namePart type="family">Lake</namePart><affiliation>BIBRA International, Woodmansterne Road, Carshalton, Surrey SM5 4DS, UK</affiliation><description>Corresponding author</description><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1999</dateIssued><copyrightDate encoding="w3cdtf">1999</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">In this study the effect of some indole derivatives on xenobiotic metabolizing enzymes and xenobiotic-induced toxicity has been examined in cultured precision-cut liver slices from male Sprague–Dawley rats. While treatment of rat liver slices for 72 hours with 2–200 μm of either indole-3-carbinol (I3C) or indole-3-acetonitrile (3-ICN) had little effect on cytochrome P-450 (CYP)-dependent enzyme activities, enzyme induction was observed after in vivo administration of I3C. The treatment of rat liver slices with 50 μm 3,3′-diindolylmethane (DIM; a dimer derived from I3C under acidic conditions) for 72 hours resulted in a marked induction of CYP-dependent enzyme activities. DIM appears to be a mixed inducer of CYP in rat liver slices having effects on CYP1A, CYP2B and CYP3A subfamily isoforms. Small increases in liver slice reduced glutathione levels and glutathione S-transferase activity were also observed after DIM treatment. While aflatoxin B1 and monocrotaline produced a concentration-dependent inhibition of protein synthesis in 72-hour-cultured rat liver slices, cytotoxicity was markedly reduced in liver slices cultured with 50 μm DIM. These results demonstrate that cultured rat liver slices may be employed to evaluate the effects of chemicals derived from cruciferous and other vegetables on CYP isoforms. In addition, liver slices can also be utilized to examine the ability of such chemicals to modulate xenobiotic-induced toxicity.</abstract><note type="content">Section title: Research Section</note><note type="content">Fig. 1: Structures of indole derivatives studied.</note><note type="content">Plate. 1: Immunoblots of rat liver microsomes incubated with anti-CYP1A1 (A), anti-CYP1A2 (B) and anti-CYP2B1/2 (C). Microsomal fractions (5μg protein per lane) were prepared from control (corn oil treated; lanes 1 and 2) rats and from rats treated with 25 (lanes 3 and 4) and 100 (lanes 5 and 6) mg/kg/day I3C by oral gavage for 3 days.</note><note type="content">Fig. 2: Effect of I3C, 3-ICN and ARO on 7-ethoxyresorufin O-deethylase in cultured rat liver slices. Liver slices were cultured with 0–200 μm I3C, 0–200 μm3-ICN and 2μg ARO/ml for 72hr. Results are expressed as means±SEM of three experiments. Values significantly different from control (DMSO only treated) cultures are: ∗∗∗P<0.001.</note><note type="content">Fig. 3: Effect of I3C, 3-ICN and ARO on 7-benzoxyresorufin O-debenzylase in cultured rat liver slices. Liver slices were cultured with 0–200 μm I3C, 0–200 μm 3-ICN and 2μg ARO /ml for 72hr. Results are expressed as means±SEM of three experiments. Values significantly different from control (DMSO only treated) cultures are: ∗P<0.05; ∗∗∗P<0.001.</note><note type="content">Fig. 4: Effect of 2–200 μm DIM on 7-ethoxyresorufin O-deethylase activity in 72-hr cultured rat liver slices. Results are expressed as means of two experiments. Mean 7-ethoxyresorufin O-deethylase activity in control (DMSO only treated) liver slices was 2.80 pmol/min/mg protein.</note><note type="content">Plate. 2: Immunoblots of 72-hr cultured rat liver slice microsomal fractions incubated with anti-CYP1A2 (A) and anti-CYP3A (B). Microsomal fractions (15μg protein per lane) were prepared from pooled control (DMSO only treated; lane 1), 50 μm I3C (lane 2), 50 μm DIM (lane 3) and 2μg ARO/ml (lane 4) treated liver slices.</note><note type="content">Fig. 5: Effect of DIM on AFB1- and monocrotaline-induced cytotoxicity in cultured rat liver slices. Liver slices were cultured for 72hr with 0 and 50 μm DIM. The medium was then changed to medium containing l-[1-14C]leucine and either no toxin (control), or 5 and 20 μm AFB1, or 0.5 and 1mm monocrotaline and the slices cultured for a further 4hr. Results are expressed as means±SEM of five experiments. Values significantly different from the appropriate control are: ∗P<0.05; ∗∗P<0.01. Rates of protein synthesis in 0 and 50 μm DIM treated liver slices cultured without any toxin (control) were not significantly different (P>0.05).</note><note type="content">Table 1: Effect of I3C on relative liver weight and some parameters of hepatic xenobiotic metabolism in the rat</note><note type="content">Table 2: Effect of DIM on levels of protein, CYP isoform activities, glutathione and glutathione S-transferase in 72hr cultured rat liver slices</note><subject><genre>Keywords</genre><topic>cytochrome P-450</topic><topic>3,3′-diindolylmethane</topic><topic>enzyme induction in vitro</topic><topic>rat liver</topic><topic>precision-cut rat liver slices</topic></subject><subject><genre>Abbreviations</genre><topic>AFB1=aflatoxin B1</topic><topic>ARO=Aroclor 1254</topic><topic>CYP=cytochrome P-450</topic><topic>DIM=3,3′-diindolylmethane</topic><topic>DMSO=dimethyl sulfoxide</topic><topic>GSH=reduced glutathione</topic><topic>GSSG=oxidized glutathione</topic><topic>I3C=indole-3-carbinol</topic><topic>3-ICN=indole-3-acetonitrile</topic></subject><relatedItem type="host"><titleInfo><title>Food and Chemical Toxicology</title></titleInfo><titleInfo type="abbreviated"><title>FCT</title></titleInfo><genre type="journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">199906</dateIssued></originInfo><identifier type="ISSN">0278-6915</identifier><identifier type="PII">S0278-6915(00)X0048-8</identifier><part><date>199906</date><detail type="volume"><number>37</number><caption>vol.</caption></detail><detail type="issue"><number>6</number><caption>no.</caption></detail><extent unit="issue pages"><start>569</start><end>670</end></extent><extent unit="pages"><start>609</start><end>618</end></extent></part></relatedItem><identifier type="istex">275E4CF8E30661F255DCC690CCEF8F521DCAD7AA</identifier><identifier type="DOI">10.1016/S0278-6915(99)00026-5</identifier><identifier type="PII">S0278-6915(99)00026-5</identifier><recordInfo><recordContentSource>ELSEVIER</recordContentSource></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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