The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats

• Published in: Food and chemical toxicology 2014-01, Vol.63, p.174-185
• Main Authors: Lee, In-Chul, Kim, Sung-Hwan, Baek, Hyung-Seon, Moon, Changjong, Kang, Seong-Soo, Kim, Sung-Ho, Kim, Yun-Bae, Shin, In-Sik, Kim, Jong-Choon
• Format: Article
• Language: English
• Subjects: Allyl Compounds - pharmacology; Animals; Apoptosis - drug effects; Base Sequence; Biological and medical sciences; Blotting, Western; Carbon tetrachloride; Carbon Tetrachloride - toxicity; Caspase 3 - metabolism; Diallyl disulfide; Disulfides - pharmacology; DNA Primers; Glutathione - metabolism; Hepatotoxicity; Inflammation - prevention & control; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Medical sciences; NF-E2-Related Factor 2 - physiology; NF-kappa B - metabolism; Nuclear factor E2-related factor 2; Nuclear factor kappaB; Oxidative Stress - drug effects; Phosphorylation; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Toxicology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2013.11.006

•Diallyl disulfide showed protective effects against carbon tetrachloride-induced hepatotoxicity in rats.•It enhanced phase II detoxifying or antioxidant enzyme activities by activating nuclear factor E2-related factor 2.•It reduced hepatocellular apoptotic changes caused by carbon tetrachloride through mitochondrial pathway.•It suppressed inflammatory response by inhibiting nuclear factor kappaB activation and I kappaB phosphorylation. This study investigated the potential effect of diallyl disulfide (DADS) against carbon tetrachloride (CCl4)-induced oxidative hepatic damage and inflammatory response in rat liver. DADS at doses of 50 and 100mg/kg/day was administered orally once daily for 5days, prior to CCl4 administration. Pretreatment with DADS attenuated CCl4-induced elevated serum transaminase activities and histopathological alterations in liver. It prevented the hepatocellular apoptotic changes with induction of Bcl-2-associated X (Bax), cytochrome c, and caspase-3 caused by CCl4. An increase in the nuclear translocation of nuclear factor-kappaB (NF-κB) and phosphorylation of I kappaB alpha (IκBα) was observed in the livers of CCl4-treated rats that coincided with induction of inflammatory mediators or cytokines. In contrast, DADS inhibited NF-κB translocation and IκBα phosphorylation, and that subsequently decreased inflammatory mediators. Furthermore, DADS prevented CCl4-induced depletion of cytosolic nuclear factor E2-related factor 2 (Nrf2) and suppression of nuclear translocation of Nrf2, which, in turn, up-regulated phase II/antioxidant enzyme activities. Taken together, these results demonstrate that DADS increases the expression of phase II/antioxidant enzymes and simultaneously decreases the expression of inflammatory mediators in CCl4-induced liver injury. These findings indicate that DADS induces antioxidant defense mechanism by activating Nrf2 pathway and reduces inflammatory response by inhibiting NF-κB activation.