The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats.
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 100 mg/kg/day was administered orally once daily for 5 days, 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.
['Lee|In-Chul|IC|', 'Kim|Sung-Hwan|SH|', 'Baek|Hyung-Seon|HS|', 'Moon|Changjong|C|', 'Kang|Seong-Soo|SS|', 'Kim|Sung-Ho|SH|', 'Kim|Yun-Bae|YB|', 'Shin|In-Sik|IS|', 'Kim|Jong-Choon|JC|']
D000498:Allyl Compounds D000818:Animals D017209:Apoptosis D001483:Base Sequence D015153:Blotting, Western D002251:Carbon Tetrachloride D053148:Caspase 3 D017931:DNA Primers D004220:Disulfides D005978:Glutathione D007249:Inflammation D008099:Liver D008297:Male D051267:NF-E2-Related Factor 2 D016328:NF-kappa B D018384:Oxidative Stress D010766:Phosphorylation D051381:Rats D017207:Rats, Sprague-Dawley D060888:Real-Time Polymerase Chain Reaction
Nrf2 Diallyl disulfide Diallyl disulfide DADS Carbon tetrachloride Carbon tetrachloride Bcl-2-associated X Bax nuclear factor-kappaB NF-κB I kappaB alpha IκBα Nuclear factor E2-related factor 2 Nuclear factor E2-related factor 2 ALT ANOVA ARE AST CCl(4) CYPs Cox-2 GAPDH GPx GR GSH GSTα H&E HO-1 Hepatotoxicity IKK IL-1β IL-6 IκB kinase Keap1 Kelch like-ECH-associated protein 1 MDA NAD(P)H quinine oxidoreductase NQO1 Nuclear factor kappaB ROS RT-PCR SOD TNF-α TUNEL Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling alanine aminotransferase analysis of variance antioxidant response element aspartate aminotransferase carbon tetrachloride cyclooxygenase-2 cytochrome P450 isoenzymes diallyl disulfide glutathione S-transferase alpha glutathione peroxidase glutathione reductase glyceraldehydes-3-phosphate dehydrogenase hematoxylin and eosin heme oxygenase-1 iNOS inducible nitric oxide synthase interleukin-1β interleukin-6 malondialdehyde nuclear factor E2-related factor 2 p-IκBα phosphor-I kappa B alpha reactive oxygen species real-time polymerase chain reaction reduced glutathione superoxide dismutase tumor necrosis factor-alpha