Induction of renal oxidative stress and cell proliferation response by ferric nitrilotriacetate (Fe-NTA): diminution by soy isoflavones.
Ferric nitrilotriacetate (Fe-NTA) is a known potent nephrotoxic agent. In this communication, we report the chemopreventive effect of soy isoflavones on renal oxidative stress, toxicity and cell proliferation response in Wistar rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances gamma-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. Fe-NTA treatment also induced tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. A sharp elevation in the levels of blood urea nitrogen and serum creatinine has also been observed. Treatment of rats orally with soy isoflavones (5 mg/kg body weight and 10 mg/kg body weight) resulted in significant decreases in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Renal glutathione content (P < 0.01), glutathione metabolizing enzymes (P < 0.001) and antioxidant enzymes were also returned to normal levels (P < 0.001). Thus, our data suggest that soy isoflavones may be used as an effective chemopreventive agent against Fe-NTA-mediated renal oxidative stress, toxicity and cell proliferation response 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.
Naghma
N
Khan
Sarwat
S
Sultana
D000284:Administration, Oral; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007529:Isoflavones / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007674:Kidney Diseases / Q000378:metabolism / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D009571:Nitrilotriacetic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013025:Glycine max / Q000737:chemistry
D002273:Carcinogens; D005290:Ferric Compounds; D007529:Isoflavones; D005978:Glutathione; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate