Melittin Exerts Beneficial Effects on Paraquat-Induced Lung Injuries in Mice by Modifying Oxidative Stress and Apoptosis
Identifieur interne : 000644 ( Main/Exploration ); précédent : 000643; suivant : 000645Melittin Exerts Beneficial Effects on Paraquat-Induced Lung Injuries in Mice by Modifying Oxidative Stress and Apoptosis
Auteurs : Bishoy El-Aarag [Égypte, Japon] ; Mohamed Magdy ; Mohamed F. Alajmi ; Shaden A. M. Khalifa ; Hesham R. El-Seedi [Suède, Pakistan]Source :
- Molecules [ 1420-3049 ] ; 2019.
Abstract
Melittin (MEL) is a 26-amino acid peptide with numerous biological activities. Paraquat (PQ) is one of the most widely used herbicides, although it is extremely toxic to humans. To date, PQ poisoning has no effective treatment, and therefore the current study aimed to assess for the first time the possible effects of MEL on PQ-induced lung injuries in mice. Mice received a single intraperitoneal (IP) injection of PQ (30 mg/kg), followed by IP treatment with MEL (0.1 and 0.5 mg/kg) twice per week for four consecutive weeks. Histological alterations, oxidative stress, and apoptosis in the lungs were studied. Hematoxylin and eosin (H&E) staining indicated that MEL markedly reduced lung injuries induced by PQ. Furthermore, treatment with MEL increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity, and decreased malonaldehyde (MDA) and nitric oxide (NO) levels in lung tissue homogenates. Moreover, immunohistochemical staining showed that B-cell lymphoma-2 (Bcl-2) and survivin expressions were upregulated after MEL treatment, while Ki-67 expression was downregulated. The high dose of MEL was more effective than the low dose in all experiments. In summary, MEL efficiently reduced PQ-induced lung injuries in mice. Specific pharmacological examinations are required to determine the effectiveness of MEL in cases of human PQ poisoning.
Url:
DOI: 10.3390/molecules24081498
PubMed: 30995821
PubMed Central: 6514788
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Melittin Exerts Beneficial Effects on Paraquat-Induced Lung Injuries in Mice by Modifying Oxidative Stress and Apoptosis</title><author><name sortKey="El Aarag, Bishoy" sort="El Aarag, Bishoy" uniqKey="El Aarag B" first="Bishoy" last="El-Aarag">Bishoy El-Aarag</name><affiliation wicri:level="1"><nlm:aff id="af1-molecules-24-01498">Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt</nlm:aff><country xml:lang="fr">Égypte</country><wicri:regionArea>Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom 32512</wicri:regionArea><wicri:noRegion>Shebin El-Koom 32512</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-01498">Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530</wicri:regionArea><wicri:noRegion>Okayama 7008530</wicri:noRegion></affiliation></author><author><name sortKey="Magdy, Mohamed" sort="Magdy, Mohamed" uniqKey="Magdy M" first="Mohamed" last="Magdy">Mohamed Magdy</name><affiliation><nlm:aff id="af3-molecules-24-01498">Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt;<email>mohamed_magdy201237@yahoo.com</email> (M.M.);<email>hesham.el-seedi@ilk.uu.se</email> (H.R.E.-S.)</nlm:aff></affiliation></author><author><name sortKey="Alajmi, Mohamed F" sort="Alajmi, Mohamed F" uniqKey="Alajmi M" first="Mohamed F." last="Alajmi">Mohamed F. Alajmi</name><affiliation><nlm:aff id="af4-molecules-24-01498">Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;<email>malajmii@ksu.edu.sa</email></nlm:aff></affiliation></author><author><name sortKey="Khalifa, Shaden A M" sort="Khalifa, Shaden A M" uniqKey="Khalifa S" first="Shaden A. M." last="Khalifa">Shaden A. M. Khalifa</name><affiliation><nlm:aff id="af5-molecules-24-01498">Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91 Stockholm, Sweden;<email>shaden.khalifa@su.se</email></nlm:aff></affiliation></author><author><name sortKey="El Seedi, Hesham R" sort="El Seedi, Hesham R" uniqKey="El Seedi H" first="Hesham R." last="El-Seedi">Hesham R. El-Seedi</name><affiliation><nlm:aff id="af3-molecules-24-01498">Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt;<email>mohamed_magdy201237@yahoo.com</email> (M.M.);<email>hesham.el-seedi@ilk.uu.se</email> (H.R.E.-S.)</nlm:aff></affiliation><affiliation wicri:level="4"><nlm:aff id="af6-molecules-24-01498">Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, SE-75123 Uppsala, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, SE-75123 Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af7-molecules-24-01498">International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan</nlm:aff><country xml:lang="fr">Pakistan</country><wicri:regionArea>International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270</wicri:regionArea><wicri:noRegion>Karachi-75270</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">30995821</idno><idno type="pmc">6514788</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514788</idno><idno type="RBID">PMC:6514788</idno><idno type="doi">10.3390/molecules24081498</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000712</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000712</idno><idno type="wicri:Area/Pmc/Curation">000712</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000712</idno><idno type="wicri:Area/Pmc/Checkpoint">000594</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000594</idno><idno type="wicri:Area/Ncbi/Merge">000546</idno><idno type="wicri:Area/Ncbi/Curation">000546</idno><idno type="wicri:Area/Ncbi/Checkpoint">000546</idno><idno type="wicri:Area/Main/Merge">000644</idno><idno type="wicri:Area/Main/Curation">000644</idno><idno type="wicri:Area/Main/Exploration">000644</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Melittin Exerts Beneficial Effects on Paraquat-Induced Lung Injuries in Mice by Modifying Oxidative Stress and Apoptosis</title><author><name sortKey="El Aarag, Bishoy" sort="El Aarag, Bishoy" uniqKey="El Aarag B" first="Bishoy" last="El-Aarag">Bishoy El-Aarag</name><affiliation wicri:level="1"><nlm:aff id="af1-molecules-24-01498">Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt</nlm:aff><country xml:lang="fr">Égypte</country><wicri:regionArea>Biochemistry Division, Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom 32512</wicri:regionArea><wicri:noRegion>Shebin El-Koom 32512</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-01498">Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530, Japan</nlm:aff><country xml:lang="fr">Japon</country><wicri:regionArea>Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama 7008530</wicri:regionArea><wicri:noRegion>Okayama 7008530</wicri:noRegion></affiliation></author><author><name sortKey="Magdy, Mohamed" sort="Magdy, Mohamed" uniqKey="Magdy M" first="Mohamed" last="Magdy">Mohamed Magdy</name><affiliation><nlm:aff id="af3-molecules-24-01498">Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt;<email>mohamed_magdy201237@yahoo.com</email> (M.M.);<email>hesham.el-seedi@ilk.uu.se</email> (H.R.E.-S.)</nlm:aff></affiliation></author><author><name sortKey="Alajmi, Mohamed F" sort="Alajmi, Mohamed F" uniqKey="Alajmi M" first="Mohamed F." last="Alajmi">Mohamed F. Alajmi</name><affiliation><nlm:aff id="af4-molecules-24-01498">Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;<email>malajmii@ksu.edu.sa</email></nlm:aff></affiliation></author><author><name sortKey="Khalifa, Shaden A M" sort="Khalifa, Shaden A M" uniqKey="Khalifa S" first="Shaden A. M." last="Khalifa">Shaden A. M. Khalifa</name><affiliation><nlm:aff id="af5-molecules-24-01498">Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, S-106 91 Stockholm, Sweden;<email>shaden.khalifa@su.se</email></nlm:aff></affiliation></author><author><name sortKey="El Seedi, Hesham R" sort="El Seedi, Hesham R" uniqKey="El Seedi H" first="Hesham R." last="El-Seedi">Hesham R. El-Seedi</name><affiliation><nlm:aff id="af3-molecules-24-01498">Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koom 32512, Egypt;<email>mohamed_magdy201237@yahoo.com</email> (M.M.);<email>hesham.el-seedi@ilk.uu.se</email> (H.R.E.-S.)</nlm:aff></affiliation><affiliation wicri:level="4"><nlm:aff id="af6-molecules-24-01498">Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, SE-75123 Uppsala, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre, Box 574, SE-75123 Uppsala</wicri:regionArea><orgName type="university">Université d'Uppsala</orgName><placeName><settlement type="city">Uppsala</settlement><region nuts="1">Svealand</region><region nuts="1">East Middle Sweden</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="af7-molecules-24-01498">International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan</nlm:aff><country xml:lang="fr">Pakistan</country><wicri:regionArea>International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270</wicri:regionArea><wicri:noRegion>Karachi-75270</wicri:noRegion></affiliation></author></analytic><series><title level="j">Molecules</title><idno type="eISSN">1420-3049</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Melittin (MEL) is a 26-amino acid peptide with numerous biological activities. Paraquat (PQ) is one of the most widely used herbicides, although it is extremely toxic to humans. To date, PQ poisoning has no effective treatment, and therefore the current study aimed to assess for the first time the possible effects of MEL on PQ-induced lung injuries in mice. Mice received a single intraperitoneal (IP) injection of PQ (30 mg/kg), followed by IP treatment with MEL (0.1 and 0.5 mg/kg) twice per week for four consecutive weeks. Histological alterations, oxidative stress, and apoptosis in the lungs were studied. Hematoxylin and eosin (H&E) staining indicated that MEL markedly reduced lung injuries induced by PQ. Furthermore, treatment with MEL increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity, and decreased malonaldehyde (MDA) and nitric oxide (NO) levels in lung tissue homogenates. Moreover, immunohistochemical staining showed that B-cell lymphoma-2 (Bcl-2) and survivin expressions were upregulated after MEL treatment, while Ki-67 expression was downregulated. The high dose of MEL was more effective than the low dose in all experiments. In summary, MEL efficiently reduced PQ-induced lung injuries in mice. Specific pharmacological examinations are required to determine the effectiveness of MEL in cases of human PQ poisoning.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Tortorelli, M C" uniqKey="Tortorelli M">M.C. Tortorelli</name></author><author><name sortKey="Hernandez, D A" uniqKey="Hernandez D">D.A. Hernandez</name></author><author><name sortKey="Rey Vazquez, G" uniqKey="Rey Vazquez G">G. Rey Vazquez</name></author><author><name sortKey="Salibian, A" uniqKey="Salibian A">A. Salibian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baltazar, T" uniqKey="Baltazar T">T. 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Khalifa</name><name sortKey="Magdy, Mohamed" sort="Magdy, Mohamed" uniqKey="Magdy M" first="Mohamed" last="Magdy">Mohamed Magdy</name></noCountry><country name="Égypte"><noRegion><name sortKey="El Aarag, Bishoy" sort="El Aarag, Bishoy" uniqKey="El Aarag B" first="Bishoy" last="El-Aarag">Bishoy El-Aarag</name></noRegion></country><country name="Japon"><noRegion><name sortKey="El Aarag, Bishoy" sort="El Aarag, Bishoy" uniqKey="El Aarag B" first="Bishoy" last="El-Aarag">Bishoy El-Aarag</name></noRegion></country><country name="Suède"><region name="Svealand"><name sortKey="El Seedi, Hesham R" sort="El Seedi, Hesham R" uniqKey="El Seedi H" first="Hesham R." last="El-Seedi">Hesham R. El-Seedi</name></region></country><country name="Pakistan"><noRegion><name sortKey="El Seedi, Hesham R" sort="El Seedi, Hesham R" uniqKey="El Seedi H" first="Hesham R." last="El-Seedi">Hesham R. El-Seedi</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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