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

Cited 30 time in scopus
Metadata Downloads
Title
Protective effects of diallyl disulfide on carbon tetrachloride-induced hepatotoxicity through activation of Nrf2
Author(s)
In Chul Lee; S H Kim; H S Baek; C Moon; S H Kim; Y B Kim; Woon Kee YoonHyoung-Chin Kim; J C Kim
Bibliographic Citation
Environmental Toxicology, vol. 30, no. 5, pp. 538-548
Publication Year
2015
Abstract
This study was conducted to investigate the potential effects of diallyl disulfide (DADS) on carbon tetrachloride (CCl4)-induced acute hepatotoxicity and to determine the molecular mechanisms of protection offered by DADS in rats. DADS was administered orally at 50 and 100 mg/kg/day once daily for 5 consecutive days prior to CCl4 administration. The single oral dose of CCl4 (2 mL/kg) caused a significant elevation in serum aspartate and alanine aminotransferase activities, which decreased upon pretreatment with DADS. Histopathological examinations showed extensive liver injury, characterized by extensive hepatocellular degeneration/necrosis, fatty changes, inflammatory cell infiltration, and congestion, which were reversed following pretreatment with DADS. The effects of DADS on cytochrome P450 2E1 (CYP2E1), the major isozyme involved in CCl4 bioactivation, were also investigated. DADS pretreatment resulted in a significant decrease in CYP2E1 protein levels in dose-dependent manner. In addition, CCl4 caused a decrease in protein level of cytoplasmic nuclear factor E2-related factor 2 (Nrf2) and suppression of nuclear translocation of Nrf2 concurrent with downregulation of detoxifying phase II enzymes and a decrease in antioxidant enzyme activities. In contrast, DADS prevented the depletion of cytoplasmic Nrf2 and enhanced nuclear translocation of Nrf2, which, in turn, upregulated antioxidant and/or phase II enzymes. These results indicate that the protective effects of DADS against CCl4-induced hepatotoxicity possibly involve mechanisms related to its ability to induce antioxidant or detoxifying enzymes by activating Nrf2 and block metabolic activation of CCl4 by suppressing CYP2E1.
Keyword
Carbon tetrachlorideCytochrome P450 2E1Diallyl disulfideHepatotoxicityNuclear factor E2-related factor 2
ISSN
1520-4081
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/tox.21930
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Functional Biomaterial Research Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
Ochang Branch Institute > Division of Bioinfrastructure > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.