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Article: Protective effect of diallyl sulfone against acetaminophen-induced hepatotoxicity in mice

TitleProtective effect of diallyl sulfone against acetaminophen-induced hepatotoxicity in mice
Authors
Issue Date1996
Citation
Journal Of Biochemical Toxicology, 1996, v. 11 n. 1, p. 11-20 How to Cite?
AbstractDiallyl sulfone (DASO2) is a metabolite of diallyl sulfide, a compound derived from garlic. The present study investigated the effect of DASO2 as a protective agent against acetaminophen (APAP)-induced hepatotoxicity in mice. Oral administration of DASO2 protected mice against the APAP-induced hepatotoxicity in a dose-and time-dependent manner. When administrated 1 hour prior to, immediately after, or 20 minutes after a toxic dose of APAP, DASO2 at a dose of 25 mg/kg completely protected mice from development of hepatotoxicity, as indicated by liver histopathology and serum lactate dehydrogenase levels. Protective effect was observed when DASO2 at a dose as low as 5 mg/kg was given to mice 1 hour prior to APAP administration. Oral administration of DASO2 to mice 1 hour prior to a toxic dose of APAP significantly inhibited the APAP-induced glutathione depletion in the liver. DASO2 treatment also decreased the levels of oxidative APAP metabolites in the plasma without affecting the concentrations of nonoxidative APAP metabolites. In liver microsomes, 0.1 mM of DASO2 caused a 60% decrease in the rate of APAP oxidation to IV-acetyl-p-benzoquinone imine, which was determined as glutathione conjugate. This inhibitory effect is mainly due to its inhibition of cytochrome P450 2E1 activity; with an IC50 value equal to 0.11 mM. DASO2 also slightly inhibited the activities of P450s 3A and 1A, with IC50 values >5 mM. Furthermore, a single oral dose of DASO2 inactivated P450 2E1- and P450 1A-dependent activities in liver microsomes. The results suggest that the protective effect of DASO2 against APAP-induced hepatotoxicity is due to its ability to block acetaminophen bioactivation mainly by the inactivation and inhibition of P450 2E1. © 1996 John Wiley & Sons, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/167553
ISSN
References

 

DC FieldValueLanguage
dc.contributor.authorLin, MCen_US
dc.contributor.authorWang, EJen_US
dc.contributor.authorPatten, Cen_US
dc.contributor.authorLee, MJen_US
dc.contributor.authorXiao, Fen_US
dc.contributor.authorReuhl, KRen_US
dc.contributor.authorYang, CSen_US
dc.date.accessioned2012-10-08T03:08:27Z-
dc.date.available2012-10-08T03:08:27Z-
dc.date.issued1996en_US
dc.identifier.citationJournal Of Biochemical Toxicology, 1996, v. 11 n. 1, p. 11-20en_US
dc.identifier.issn0887-2082en_US
dc.identifier.urihttp://hdl.handle.net/10722/167553-
dc.description.abstractDiallyl sulfone (DASO2) is a metabolite of diallyl sulfide, a compound derived from garlic. The present study investigated the effect of DASO2 as a protective agent against acetaminophen (APAP)-induced hepatotoxicity in mice. Oral administration of DASO2 protected mice against the APAP-induced hepatotoxicity in a dose-and time-dependent manner. When administrated 1 hour prior to, immediately after, or 20 minutes after a toxic dose of APAP, DASO2 at a dose of 25 mg/kg completely protected mice from development of hepatotoxicity, as indicated by liver histopathology and serum lactate dehydrogenase levels. Protective effect was observed when DASO2 at a dose as low as 5 mg/kg was given to mice 1 hour prior to APAP administration. Oral administration of DASO2 to mice 1 hour prior to a toxic dose of APAP significantly inhibited the APAP-induced glutathione depletion in the liver. DASO2 treatment also decreased the levels of oxidative APAP metabolites in the plasma without affecting the concentrations of nonoxidative APAP metabolites. In liver microsomes, 0.1 mM of DASO2 caused a 60% decrease in the rate of APAP oxidation to IV-acetyl-p-benzoquinone imine, which was determined as glutathione conjugate. This inhibitory effect is mainly due to its inhibition of cytochrome P450 2E1 activity; with an IC50 value equal to 0.11 mM. DASO2 also slightly inhibited the activities of P450s 3A and 1A, with IC50 values >5 mM. Furthermore, a single oral dose of DASO2 inactivated P450 2E1- and P450 1A-dependent activities in liver microsomes. The results suggest that the protective effect of DASO2 against APAP-induced hepatotoxicity is due to its ability to block acetaminophen bioactivation mainly by the inactivation and inhibition of P450 2E1. © 1996 John Wiley & Sons, Inc.en_US
dc.languageengen_US
dc.relation.ispartofJournal of Biochemical Toxicologyen_US
dc.subject.meshAcetaminophen - Administration & Dosage - Toxicityen_US
dc.subject.meshAdministration, Oralen_US
dc.subject.meshAllyl Compounds - Administration & Dosage - Pharmacologyen_US
dc.subject.meshAnalgesics, Non-Narcotic - Administration & Dosage - Toxicityen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBenzoquinones - Metabolismen_US
dc.subject.meshChromatography, High Pressure Liquiden_US
dc.subject.meshCytochrome P-450 Cyp2e1 - Antagonists & Inhibitorsen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshGlutathione - Metabolismen_US
dc.subject.meshImines - Metabolismen_US
dc.subject.meshL-Lactate Dehydrogenase - Blooden_US
dc.subject.meshLiver - Drug Effects - Enzymology - Injuries - Pathologyen_US
dc.subject.meshMaleen_US
dc.subject.meshMiceen_US
dc.subject.meshMicrosomes, Liver - Drug Effects - Metabolismen_US
dc.subject.meshOxidation-Reductionen_US
dc.subject.meshSulfones - Administration & Dosage - Pharmacologyen_US
dc.titleProtective effect of diallyl sulfone against acetaminophen-induced hepatotoxicity in miceen_US
dc.typeArticleen_US
dc.identifier.emailLin, MC:mcllin@hkucc.hku.hken_US
dc.identifier.authorityLin, MC=rp00746en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid8806047-
dc.identifier.scopuseid_2-s2.0-0030367945en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0030367945&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume11en_US
dc.identifier.issue1en_US
dc.identifier.spage11en_US
dc.identifier.epage20en_US
dc.identifier.scopusauthoridLin, MC=7404816359en_US
dc.identifier.scopusauthoridWang, EJ=7403414471en_US
dc.identifier.scopusauthoridPatten, C=7006031499en_US
dc.identifier.scopusauthoridLee, MJ=37022719700en_US
dc.identifier.scopusauthoridXiao, F=7201709646en_US
dc.identifier.scopusauthoridReuhl, KR=7006483839en_US
dc.identifier.scopusauthoridYang, CS=36037810500en_US

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