Inhibitory effects of melatonin on ferric nitrilotriacetate-induced lipid peroxidation and oxidative DNA damage in the rat kidney

Ferric nitrilotriacetate (Fe-NTA) is a known complete renal carcinogen whic h induces lipid peroxidation and oxidative DNA damage in rat kidney. In thi s study, the in vivo and in vitro effects of melatonin on Fe-NTA-induced li pid and oxidative DNA damage were determined. The levels of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) were assayed as an index of lipid pero xidation and the levels of 8-hydroxydeoxyguanosine (8-OH-dG) as an endpoint of oxidative DNA damage. In in vitro studies, the increased levels of MDA and 4-HDA induced by Fe-NTA were observed to be dose-dependent and time-dep endent. The increase in lipid peroxidation was inhibited by melatonin in a concentration-dependent manner. When Fe-NTA(IS mg Fe/kg body weight) was in traperitoneally injected into rats, the levels of MDA+4-HDA and 8-OH-dG in the rat kidney were increased 1 h after its administration as compared to l evels of these constituents in the control group. Pretreatment with melaton in (25 mg/kg or 50 mg/kg) 30 min before the Fe-NTA injection resulted in a significant reduction in the levels of lipid peroxidation and 8-OH-dG induc ed by Fe-NTA in the rat kidney. These results are consistent with the concl usion that the toxicity of Fe-NTA is due to the generation of reactive oxyg en species and that melatonin's protective effects relate to its direct rad ical scavenging ability and due to other antioxidative processes induced by the indole. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.