Allyl methyl trisulfide protected against acetaminophen (paracetamol)-induced hepatotoxicity by suppressing CYP2E1 and activating Nrf2 in mouse liver

• Published in: Food & function Vol. 10; no. 4; pp. 2244 - 2253
• Main Authors: Zhao, Hui-Juan, Li, Ming-Jun, Zhang, Meng-Ping, Wei, Meng-Ke, Shen, Li-Ping, Jiang, Min, Zeng, Tao
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 01.04.2019
• Subjects: Acetaminophen; Analgesics; Attenuation; Corn oil; CYP2E1 protein; Hepatotoxicity; Liver; Malondialdehyde; Mice; Morphology; Overdose; Paracetamol; Pretreatment; Proteins; Rodents
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/c9fo00170k

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 AMTS or corn oil for 7 d followed by intraperitoneal injection of 300 mg kg 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.