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

ABSTRACT

In 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.

KEYWORDS :

• Kidney
• Hyperproliferative Response
• Fe-NTA
• Thymidine Incorporation