Induction of renal oxidative stress and cell proliferation response by ferric nitrilotriacetate (Fe-NTA): diminution by soy isoflavones.

Abstract

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.

• Authors: Naghma Khan, Sarwat Sultana
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 149 Issue 1 Pg. 23-35 (Aug 10 2004) ISSN: 0009-2797 [Print] Ireland
• PMID: 15294441 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• Ferric Compounds
• Isoflavones
• Glutathione
• Nitrilotriacetic Acid
• ferric nitrilotriacetate

Topics

• Administration, Oral
• Animals
• Carcinogens (administration & dosage, toxicity)
• Cell Division (drug effects)
• DNA Replication (drug effects)
• Drug Therapy, Combination
• Female
• Ferric Compounds (administration & dosage, antagonists & inhibitors, toxicity)
• Glutathione (metabolism)
• Injections, Intraperitoneal
• Isoflavones (administration & dosage, pharmacology)
• Kidney (drug effects, enzymology)
• Kidney Diseases (metabolism, prevention & control)
• Lipid Peroxidation (drug effects)
• Microsomes (drug effects, enzymology)
• Nitrilotriacetic Acid (administration & dosage, analogs & derivatives, antagonists & inhibitors, toxicity)
• Oxidative Stress (drug effects)
• Rats
• Rats, Wistar
• Glycine max (chemistry)