A model of Fe-NTA induced nephrotoxicity, oxidative stress and early tumor promotion markers in experimental rats: protective effect of butylate hydroxyanisole

Abstract

Background: In this study the protective effect of butylated hydroxyanisole (BHA), a phenolic antioxidant used in foods, on Ferric-Nitrilotriacetate (Fe–NTA) induced nephrotoxicity is reported. Materials and Methods: Male albino rats of Wistar strain (4–6 weeks old) weighing 125–150 g were used in this study. Animals were given a single dose of Fe-NTA (9 mg/kg body weight,intraperitoneal) after a week of treatment with BHA (1 and 2 mg/animal/day). Results: Fe-NTA treatment enhanced ornithine decarboxylase activity to 5.3 fold, and [3H] thymidine incorporation in DNA to 2.5 fold in kidney compared with the corresponding saline treated control whereas glutathione levels and the activities of antioxidant enzymes decreased to a range of 2–2.5 fold in kidney. These changes were reversed significantly in animals receiving a pretreatment of BHA. The enhanced ornithine decarboxylase activity and DNA synthesis showed a reduction to 2.12 fold and 1.15 fold respectively at a higher dose of 2 mg BHA/day/animal, compared with the Fe-NTA treated groups. Pretreatment with BHA prior to Fe-NTA treatment increased glutathione and the activities of antioxidant enzymes to a range of 1.5-2 folds in kidney. Conclusion: The results indicate that BHA is a potent chemopreventive agent and suppresses Fe-NTA induced nephrotoxicity in male wistar rats. However, a major concern which must be addressed when extrapolating animal findings to humans is the dosage of the agent studied.