Tumor Promotion and Oxidative Stress in Ferric Nitrilotriacetate–Mediated Renal Carcinogenesis: Protection by Adhatoda vasica

Abstract

ABSTRACTIn the present study, we report the chemopreventive effects of Adhatoda vasica against ferric nitrilotriacetate (Fe-NTA)–induced renal oxidative stress, hyperproliferative response, and two-stage renal carcinogenesis. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances renal lipid peroxidation, xanthine oxidase (XO), and hydrogen peroxide (H2O2) generation with concomitant reduction in renal glutathione content (GSH), antioxidant enzymes, and phase II metabolizing enzymes. It induces blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity, and [3H] thymidine incorporation into renal DNA. It also enhances DEN (N-diethylnitrosamine)-initiated renal carcinogenesis by increasing the percentage incidences of kidney tumors. Pretreatment of rats orally with A. vasica (50 and 100 mg/kg body weight) resulted in a significant decrease in lipid peroxidation, H2O2 generation, xanthine oxidase (XO), blood urea nitrogen, serum creatinine, renal ODC activity, DNA synthesis (p < 0.001), and incidence of tumors. Renal GSH (p < 0.01), glutathione-metabolizing enzymes (p < 0.001), and antioxidant enzymes were also recovered significantly (p < 0.001). Thus, our results show that A. vasica may meet the criteria demanded from a chemopreventive agent and in a rodent system it can reduce hyperproliferative response toxicity and carcinogenic activity of Fe-NTA.