期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 46, 期 4, 页码 1279-1287出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2007.09.095
关键词
curcumin; tetrahydrocurcumin; heme oxygenase-1; Nrf2; hepatoprotection; ARE
资金
- National Research Foundation of Korea [2004-02482, 과C6A2102] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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