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 which induces lipid peroxidation and oxidative DNA damage in rat kidney. In this study, the in vivo and in vitro effects of melatonin on Fe-NTA-induced lipid and oxidative DNA damage were determined. The levels of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) were assayed as an index of lipid peroxidation 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-dependent. The increase in lipid peroxidation was inhibited by melatonin in a concentration-dependent manner. When Fe-NTA(15 mg Fe/kg body weight) was intraperitoneally 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 levels of these constituents in the control group. Pretreatment with melatonin (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 induced by Fe-NTA in the rat kidney. These results are consistent with the conclusion that the toxicity of Fe-NTA is due to the generation of reactive oxygen species and that melatonin's protective effects relate to its direct radical scavenging ability and due to other antioxidative processes induced by the indole.
Qi
W
W
Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio 78284-7762, USA.
Reiter
R J
RJ
Tan
D X
DX
Manchester
L C
LC
Kim
S J
SJ
Garcia
J J
JJ
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000633:toxicity; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002273:Carcinogens; D005290:Ferric Compounds; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D008550:Melatonin; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate