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Curcumin attenuates dimethylnitrosamine-induced liver injury in rats through Nrf2-mediated induction of heme oxygenase-1

Cited 208 time in Web of Science Cited 229 time in Scopus
Authors
Farombi, E. Olatunde; Shrotriya, Sangeeta; Na, Hye-Kyung; Kim, Sung-Hoon; Surh, Young-Joon
Issue Date
2008-04
Citation
Food and Chemical Toxicology, Vol.46 No.4, pp.1279-1287
Keywords
curcumintetrahydrocurcuminheme oxygenase-1Nrf2hepatoprotectionARE
Abstract
Curcumin (diferuloymethane), a yellow colouring agent present in the rhizome of Curcunta longs 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 200 mg/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. (c) 2007 Elsevier Ltd. All rights reserved.
ISSN
0278-6915
URI
https://hdl.handle.net/10371/172707
DOI
https://doi.org/10.1016/j.fct.2007.09.095
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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