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Food Funct ; 10(4): 2244-2253, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30958500

RESUMO

In order to investigate the protective effects of allyl methyl trisulfide (AMTS) on acetaminophen (APAP)-induced hepatotoxicity, 75 KM mice were randomized into 5 groups, i.e. a control group, an APAP group, and three AMTS/APAP groups. The mice in the AMTS/APAP groups and APAP group were gavaged with 25-100 mg kg-1 AMTS or corn oil for 7 d followed by intraperitoneal injection of 300 mg kg-1 APAP, while mice in the control group were treated with a vehicle. We found that AMTS significantly attenuated APAP-induced hepatotoxicity shown by reduced mortality, decreased serum aminotransferase activities, and improved liver histological morphology. APAP overdose resulted in a significant increase of hepatic malondialdehyde (MDA) level and a decrease of the protein levels of NQO-1, γ-GCS, HO-1, and SOD, which was suppressed by AMTS pretreatment. Furthermore, AMTS inhibited the APAP-induced elevation of hepatic p62 and LC3II protein levels. Interestingly, AMTS attenuated the APAP-induced decline of hepatic CYP2E1 protein levels, but AMTS alone led to the decrease of CYP2E1 protein expression in mouse liver. Collectively, these data suggest that AMTS could attenuate APAP-induced hepatotoxicity by suppressing CYP2E1 and activating Nrf2.


Assuntos
Acetaminofen/efeitos adversos , Compostos Alílicos/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Citocromo P-450 CYP2E1/metabolismo , Fígado/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Protetoras/administração & dosagem , Sulfetos/administração & dosagem , Alanina Transaminase/sangue , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Citocromo P-450 CYP2E1/genética , Glutationa/metabolismo , Fígado/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo
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