Amelioration of ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and tumor promotion response by coumarin (1,2-benzopyrone) in Wistar rats

Khan, Naghma; Sharma, Sonia; Sultana, Sarwat

doi:10.1016/j.canlet.2004.01.011

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Volume 210, Issue 1 , Pages 17-26, 8 July 2004

Amelioration of ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and tumor promotion response by coumarin (1,2-benzopyrone) in Wistar rats

Section of Chemoprevention and Nutrition Toxicology, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi 110 062, India

Received 30 September 2003; received in revised form 14 January 2004; accepted 15 January 2004.

Abstract

In this study, we report the modulatory effect of coumarin (1,2-benzopyrone) on Ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and tumor promotion response in rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase, γ-glutamyl transpeptidase and hydrogen peroxide (H₂O₂) generation with reduction in antioxidant enzymes and renal glutathione content. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and thymidine [³H] incorporation into renal DNA. Prophylactic treatment of rats with coumarin (10 and 20 mg/kg body weight) resulted in significant recovery of antioxidant enzymes (P<0.001) and renal glutathione content (P<0.01). There was also significant decrease in γ-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H₂O₂ generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P<0.001). Thus, our results show that coumarin is a potent chemopreventive agent and suppresses Fe-NTA induced nephrotoxicity in Wistar rats.

Keywords: Coumarin, Ferric nitrilotriacetate, Tumor promotion response, Oxidative stress