Glyceryl trinitrate, a nitric oxide donor, abrogates ferric nitrilotriacetate-induced oxidative stress and renal damage.
Ferric nitrilotriacetate (Fe-NTA), a common water pollutant and a known renal carcinogen, acts through the generation of oxidative stress and hyperproliferative response. In the present study, we show that the nitric oxide (NO) generated by the administration of glyceryl trinitrate (GTN) affords protection against Fe-NTA-induced oxidative stress and proliferative response. Administration of Fe-NTA resulted in a significant (P<0.001) depletion of renal glutathione (GSH) content with concomitant increase in lipid peroxidation and elevated tissue damage marker release in serum. Parallel to these changes, Fe-NTA also caused down-regulation of GSH metabolizing enzymes including glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase and several fold induction in ornithine decarboxylase (ODC) activity and rate of DNA synthesis. Subsequent exogenous administration of GTN at doses of 3 and 6mg/kg body weight resulted in significant (P<0.001) recovery of GSH metabolizing enzymes and amelioration of tissue GSH content, in a dose-dependent manner. GTN administration also inhibited malondialdehyde (MDA) formation, induction of ODC activity, enhanced rate of DNA synthesis, and pathological deterioration in a dose-dependent fashion. Further, administration of NO inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), exacerbated Fe-NTA-induced oxidative tissue injury, hyperproliferative response, and pathological damage. Overall, the study suggests that NO administration subsequent to Fe-NTA affords protection against ROS-mediated damage induced by Fe-NTA.
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005290:Ferric Compounds / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity*; D005996:Nitroglycerin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D002273:Carcinogens; D004791:Enzyme Inhibitors; D005290:Ferric Compounds; D020030:Nitric Oxide Donors; D005996:Nitroglycerin; D009571:Nitrilotriacetic Acid; D019331:NG-Nitroarginine Methyl Ester; C020326:ferric nitrilotriacetate