Protective effects of diallyl disulfide on carbon tetrachloride-induced hepatotoxicity through activation of Nrf2

• DOI: 10.1002/tox.21930
• Publication Date: 2013-12-02T04:50:51Z
• Authors: In-Chul Lee; Sung-Hwan Kim; Hyung-Seon Baek; Changjong Moon; Sung-Ho Kim; Yun-Bae Kim; Won-Kee Yun; Hyoung-Chin Kim; Jong-Choon Kim
• Keywords: Diallyl disulfide; CCL4

This study was conducted to investigate the potential effects of diallyl disulfide (DADS) on carbon tetrachloride (CCl4)-induced acute hepatotoxicity and determine molecular mechanisms protection offered by DADS in rats. administered orally at 50 100 mg/kg/day once daily for 5 consecutive days prior CCl4 administration. The single oral dose (2 mL/kg) caused a significant elevation serum aspartate alanine aminotransferase activities, which decreased upon pretreatment with DADS. Histopathological examinations showed extensive liver injury, characterized hepatocellular degeneration/necrosis, fatty changes, inflammatory cell infiltration, congestion, were reversed following cytochrome P450 2E1 (CYP2E1), major isozyme involved bioactivation, also investigated. resulted decrease CYP2E1 protein levels dose-dependent manner. In addition, level cytoplasmic nuclear factor E2-related 2 (Nrf2) suppression translocation Nrf2 concurrent downregulation detoxifying phase II enzymes antioxidant enzyme activities. contrast, prevented depletion enhanced Nrf2, which, turn, upregulated and/or enzymes. These results indicate that protective against CCl4-induced possibly involve related its ability induce or activating block metabolic activation suppressing CYP2E1. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 538–548, 2015.