ATTENUATION OF IRON-NITRILOTRIACETATE (FE-NTA)-MEDIATED RENAL OXIDATIVE STRESS, TOXICITY AND HYPERPROLIFERATIVE RESPONSE BY THE PROPHYLACTIC TREATMENT OF RATS WITH GARLIC OIL

Iron nitrilotriacetate (Fe-NTA) is a potent nephrotoxic agent.In this communication we show that Fe-NTA-mediated nephrotoxicity is diminishe d by 1 wk of oral daily pretreatment of male albino Wistar rats with g arlic oil given by gavage at 50 or 100 mg/kg body weight/ml corn oil. Intraperitoneal Fe-NTA treatment at a dose level of 9 mg Fe/kg body we ight/10 ml enhances renal microsomal lipid peroxidation and hydrogen p eroxide generation which are accompanied by a decrease in the activiti es of renal antioxidant enzymes (e.g. catalase,glutathione peroxidase, glutathione reductase and glutathione S-transferase), and a depletion in the level of renal glutathione. Parallel to these changes, a sharp increase in blood urea nitrogen and serum creatinine has been observe d. In addition, Fe-NTA treatment also enhances renal ornithine decarbo xylase (ODC) activity and increases [H-3]thymidine incorporation into renal DNA. Prophylactic treatment of-animals with garlic oil before th e administration of Fe-NTA resulted in the diminution of Fe-NTA mediat ed injury. The enhancement of renal lipid peroxidation and hydrogen pe roxide generation was decreased. In addition, there was recovery of gl utathione depletion and inhibition of the activities of antioxidant en zymes. Similarly, in animals given the higher dose of garlic oil (100 mg/kg body weight) the enhanced blood urea nitrogen and serum creatini ne levels, which are indicative of renal injury, showed a reduction of about 30% and 40%, respectively, in comparison with the group treated with Fe-NTA alone. Pretreatment with garlic oil also ameliorated the Fe-NTA-mediated induction of ODC activity and enhancement of [H-3]thym idine incorporation into DNA in a dose-dependent manner. Our data sugg est that garlic oil is a potent chemopreventive agent and may suppress Fe-NTA-induced nephrotoxicity. (C) 1998 Elsevier Science Ltd. All rig hts reserved.