Potential adverse effects of oseltamivir in rats: males are more vulnerable than females.
Identifieur interne : 001529 ( Main/Exploration ); précédent : 001528; suivant : 001530Potential adverse effects of oseltamivir in rats: males are more vulnerable than females.
Auteurs : Wael M. El-Sayed ; Mohamed Ali Al-KahtaniSource :
- Canadian journal of physiology and pharmacology [ 1205-7541 ] ; 2011.
Descripteurs français
- KwdFr :
- MESH :
- effets indésirables : Antiviraux, Oséltamivir.
- enzymologie : Foie.
- sang : Lipides.
- Animaux, Caractères sexuels, Femelle, Foie, Mâle, Peroxydation lipidique, Rat Wistar, Rein.
English descriptors
- KwdEn :
- MESH :
- chemical , adverse effects : Antiviral Agents, Oseltamivir.
- chemical , blood : Lipids.
- drug effects : Kidney, Lipid Peroxidation, Liver.
- enzymology : Liver.
- Animals, Female, Male, Rats, Wistar, Sex Characteristics.
Abstract
Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140-170 g). Oseltamivir was administered at 2.2 mg·kg(-1)·day(-1) for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.
DOI: 10.1139/y11-060
PubMed: 21861687
Affiliations:
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El-Sayed</name><affiliation><nlm:affiliation>King Faisal University, Faculty of Science, Department of Biological Sciences, Al-Hufof 31982, Ahsaa, KSA.</nlm:affiliation><wicri:noCountry code="subField">KSA</wicri:noCountry></affiliation></author><author><name sortKey="Al Kahtani, Mohamed Ali" sort="Al Kahtani, Mohamed Ali" uniqKey="Al Kahtani M" first="Mohamed Ali" last="Al-Kahtani">Mohamed Ali Al-Kahtani</name><affiliation><nlm:affiliation>King Faisal University, Faculty of Science, Department of Biological Sciences, Al-Hufof 31982, Ahsaa, KSA.</nlm:affiliation><wicri:noCountry code="subField">KSA</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="RBID">pubmed:21861687</idno><idno type="pmid">21861687</idno><idno type="doi">10.1139/y11-060</idno><idno type="wicri:Area/PubMed/Corpus">000612</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000612</idno><idno type="wicri:Area/PubMed/Curation">000610</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000610</idno><idno type="wicri:Area/PubMed/Checkpoint">000616</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000616</idno><idno type="wicri:Area/Ncbi/Merge">000472</idno><idno type="wicri:Area/Ncbi/Curation">000472</idno><idno type="wicri:Area/Ncbi/Checkpoint">000472</idno><idno type="wicri:Area/Main/Merge">001531</idno><idno type="wicri:Area/Main/Curation">001529</idno><idno type="wicri:Area/Main/Exploration">001529</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Potential adverse effects of oseltamivir in rats: males are more vulnerable than females.</title><author><name sortKey="El Sayed, Wael M" sort="El Sayed, Wael M" uniqKey="El Sayed W" first="Wael M" last="El-Sayed">Wael M. El-Sayed</name><affiliation><nlm:affiliation>King Faisal University, Faculty of Science, Department of Biological Sciences, Al-Hufof 31982, Ahsaa, KSA.</nlm:affiliation><wicri:noCountry code="subField">KSA</wicri:noCountry></affiliation></author><author><name sortKey="Al Kahtani, Mohamed Ali" sort="Al Kahtani, Mohamed Ali" uniqKey="Al Kahtani M" first="Mohamed Ali" last="Al-Kahtani">Mohamed Ali Al-Kahtani</name><affiliation><nlm:affiliation>King Faisal University, Faculty of Science, Department of Biological Sciences, Al-Hufof 31982, Ahsaa, KSA.</nlm:affiliation><wicri:noCountry code="subField">KSA</wicri:noCountry></affiliation></author></analytic><series><title level="j">Canadian journal of physiology and pharmacology</title><idno type="eISSN">1205-7541</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiviral Agents (adverse effects)</term><term>Female</term><term>Kidney (drug effects)</term><term>Lipid Peroxidation (drug effects)</term><term>Lipids (blood)</term><term>Liver (drug effects)</term><term>Liver (enzymology)</term><term>Male</term><term>Oseltamivir (adverse effects)</term><term>Rats, Wistar</term><term>Sex Characteristics</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antiviraux (effets indésirables)</term><term>Caractères sexuels</term><term>Femelle</term><term>Foie ()</term><term>Foie (enzymologie)</term><term>Lipides (sang)</term><term>Mâle</term><term>Oséltamivir (effets indésirables)</term><term>Peroxydation lipidique ()</term><term>Rat Wistar</term><term>Rein ()</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiviral Agents</term><term>Oseltamivir</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Lipids</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Kidney</term><term>Lipid Peroxidation</term><term>Liver</term></keywords><keywords scheme="MESH" qualifier="effets indésirables" xml:lang="fr"><term>Antiviraux</term><term>Oséltamivir</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Foie</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Liver</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Lipides</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Female</term><term>Male</term><term>Rats, Wistar</term><term>Sex Characteristics</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Caractères sexuels</term><term>Femelle</term><term>Foie</term><term>Mâle</term><term>Peroxydation lipidique</term><term>Rat Wistar</term><term>Rein</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140-170 g). Oseltamivir was administered at 2.2 mg·kg(-1)·day(-1) for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats. </div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Al Kahtani, Mohamed Ali" sort="Al Kahtani, Mohamed Ali" uniqKey="Al Kahtani M" first="Mohamed Ali" last="Al-Kahtani">Mohamed Ali Al-Kahtani</name><name sortKey="El Sayed, Wael M" sort="El Sayed, Wael M" uniqKey="El Sayed W" first="Wael M" last="El-Sayed">Wael M. El-Sayed</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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