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Curcumin attenuates oxidative damage in animals treated with a renal carcinogen, ferric nitrilotriacetate (Fe-NTA): implications for cancer prevention

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Abstract

Curcumin (diferuloylmethane), a biologically active ingredient derived from rhizome of the plant Curcuma longa, has potent anticancer properties as demonstrated in a plethora of human cancer cell lines/animal carcinogenesis model and also acts as a biological response modifier in various disorders. We have reported previously that dietary supplementation of curcumin suppresses renal ornithine decarboxylase (Okazaki et al. Biochim Biophys Acta 1740:357–366, 2005) and enhances activities of antioxidant and phase II metabolizing enzymes in mice (Iqbal et al. Pharmacol Toxicol 92:33–38, 2003) and also inhibits Fe-NTA-induced oxidative injury of lipids and DNA in vitro (Iqbal et al. Teratog Carcinog Mutagen 1:151–160, 2003). This study was designed to examine whether curcumin possess the potential to suppress the oxidative damage caused by kidney-specific carcinogen, Fe-NTA, in animals. In accord with previous report, at 1 h after Fe-NTA treatment (9.0 mg Fe/kg body weight intraperitoneally), a substantial increased formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts in renal proximal tubules of animals was observed. Likewise, the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and protein reactive carbonyl, an indicator of protein oxidation, were also increased at 1 h after Fe-NTA treatment in the kidneys of animals. The prophylactic feeding of animals with 1.0% curcumin in diet for 4 weeks completely abolished the formation of (i) HNE-modified protein adducts, (ii) 8-OHdG, and (iii) protein reactive carbonyl in the kidneys of Fe-NTA-treated animals. Taken together, our results suggest that curcumin may afford substantial protection against oxidative damage caused by Fe-NTA, and these protective effects may be mediated via its antioxidant properties. These properties of curcumin strongly suggest that it could be used as a cancer chemopreventive agent.

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Acknowledgments

Authors are thankful to Japan Society for the Promotion of Science (JSPS) for providing grant-in-aid for scientific research to support these studies. Authors are also thankful to Dr. S. Toyokuni (Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Japan) for providing monoclonal antibody, HNEJ-2, specific for HNE-modified protein adducts and N45.1, specific for 8-OHdG, respectively. Authors are also thankful to Dr. Nur Asikin (School of Medicine, University Malaysia Sabah) for reading the manuscript and valuable suggestions.

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  1. Biotechnology Research Institute, University Malaysia Sabah, Locked Bag No. 2073, 8999, Kota Kinabalu, Sabah, Malaysia

    Mohammad Iqbal

  2. Department of Pathological Research, Faculty of Medicine, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-Cho, Okayama, 700-8558, Japan

    Yasumasa Okazaki & Shigeru Okada

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  1. Mohammad Iqbal
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  2. Yasumasa Okazaki
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Correspondence to Mohammad Iqbal.

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Iqbal, M., Okazaki, Y. & Okada, S. Curcumin attenuates oxidative damage in animals treated with a renal carcinogen, ferric nitrilotriacetate (Fe-NTA): implications for cancer prevention. Mol Cell Biochem 324, 157–164 (2009). https://doi.org/10.1007/s11010-008-9994-z

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