The effects of exogenous glutathione and cysteine on oxidative stress induced by ferric nitrilotriacetate.
The effects of the antioxidants, glutathione (GSH) and its precursor cysteine (Cys) on oxidative damage induced by ferric nitrilotriacetate (Fe-NTA) were examined. Fe-NTA-associated oxidative stress caused the depletion of renal cellular GSH content. Administration of exogenous GSH and Cys suppressed 8-hydroxydeoxyguanosine (8-OH-dG) formation, an indicator of oxidative DNA damage and nephrotoxicity following Fe-NTA treatment. This suggests that generation of free radicals may be causally involved in oxidative lesion generation. Since lipid peroxidation was found to be inhibited only by GSH and not Cys treatment, this suggests that this effect and the DNA damage might be mediated by different pathways. Fe-NTA-associated oxidative stress in renal tubular cells might thus operate via both intracellular and external space modes.
Umemura
T
T
Division of Toxicology, National Institute of Hygienic Sciences, Tokyo, Japan.
Sai
K
K
Takagi
A
A
Hasegawa
R
R
Kurokawa
Y
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D003545:Cysteine / Q000494:pharmacology*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D005290:Ferric Compounds / Q000633:toxicity*; D005609:Free Radicals; D005978:Glutathione / Q000494:pharmacology*; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000975:Antioxidants; D005290:Ferric Compounds; D005609:Free Radicals; D013438:Sulfhydryl Compounds; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005978:Glutathione; D003545:Cysteine; D009571:Nitrilotriacetic Acid; C020326:ferric nitrilotriacetate