Curcumin attenuates dimethylnitrosamine-induced liver injury in rats through Nrf2-mediated induction of heme oxygenase-1.
Curcumin (diferuloymethane), a yellow colouring agent present in the rhizome of Curcuma longa Linn (Zingiberaceae), has been reported to possess anti-inflammatory, antioxidant, antimutagenic and anticarcinogenic activities. Curcumin exerts its chemoprotective and chemopreventive effects via multiple mechanisms. It has been reported to induce expression of the antioxidant enzymes in various cell lines. Heme oxygenase-1 (HO-1) is an important antioxidant enzyme that plays a pivotal role in cytoprotection against noxious stimuli of both endogenous and exogenous origin. In the present study, we found that oral administration of curcumin at 200mg/kg dose for four consecutive days not only protected against dimethylnitrosamine (DMN)-induced hepatic injury, but also resulted in more than three-fold induction of HO-1 protein expression as well as activity in rat liver. Inhibition of HO-1 activity by zinc protoporphyrin-IX abrogated the hepatoprotective effect of curcumin against DMN toxicity. NF-E2-related factor 2 (Nrf2) plays a role in the cellular protection against oxidative stress through antioxidant response element (ARE)-directed induction of several phase-2 detoxifying and antioxidant enzymes including HO-1. Curcumin administration resulted in enhanced nuclear translocation and ARE-binding of Nrf2. Taken together, these findings suggest that curcumin protects against DMN-induced hepatotoxicity, at least in part, through ARE-driven induction of HO-1 expression.
Farombi
E Olatunde
EO
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
Shrotriya
Sangeeta
S
Na
Hye-Kyung
HK
Kim
Sung-Hoon
SH
Surh
Young-Joon
YJ
D000818:Animals; D016588:Anticarcinogenic Agents; D015153:Blotting, Western; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004128:Dimethylnitrosamine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D024202:Electrophoretic Mobility Shift Assay; D004790:Enzyme Induction / Q000187:drug effects; D004798:Enzymes / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004798:Enzymes; D051267:NF-E2-Related Factor 2; C096277:tetrahydrocurcumin; D051547:Heme Oxygenase-1; D005978:Glutathione; D003474:Curcumin; D004128:Dimethylnitrosamine