The protective role of glutathione, cysteine and vitamin C against oxidative DNA damage induced in rat kidney by potassium bromate.
The roles of glutathione (GSH), cysteine, vitamin C, liposome-encapsulated superoxide dismutase (L-SOD) and vitamin E in preventing oxidative DNA damage and cytotoxicity in the rat kidney after administration of potassium bromate (KBrO3) to male F344 rats were investigated by measuring 8-hydroxydeoxyguanosine (8-OH-dG), an oxidative DNA product, lipid peroxidation (LPO) levels and relative kidney weight (RKW). Combined pre- and posttreatment of animals with 2 x 800 mg/kg GSH i.p. inhibited the increase of 8-OH-dG, LPO levels and RKW caused by 80 mg/kg KBrO3 i.p. administration. In contrast, pretreatment with 0.3 ml/kg diethylmaleate (DEM) i.p., a depletor of tissue GSH, was associated with elevation of 8-OH-dG, LPO levels and RKW after a 20 mg/kg KBrO3 i.p. treatment, which itself caused no change. Administration of KBrO3 itself reduced renal non-protein thiol levels, but this was inhibited by the two doses of exogenous GSH. Combined treatment with DEM and KBrO3 lowered the non-protein thiol level in the kidney more than did DEM treatment alone. Protective effects against the oxidative damage caused by KBrO3 were also observed for pre- and posttreatment with 400 mg/kg cysteine i.p., another sulfhydryl compound, and daily i.g. application of 200 mg/kg vitamin C for 5 days. However, no influence was evident after pre- and posttreatment with 18,000 U/kg L-SOD i.p. or daily i.g. 100 mg/kg of vitamin E for 5 days. The results suggest that intracellular GSH plays an essential protective role against renal oxidative DNA damage and nephrotoxicity caused by KBrO3.
Sai
K
K
Division of Toxicology, National Institute of Hygienic Sciences, Tokyo.
Umemura
T
T
Takagi
A
A
Hasegawa
R
R
Kurokawa
Y
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001959:Bromates / Q000633:toxicity*; D003545:Cysteine / Q000494:pharmacology*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005978:Glutathione / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008298:Maleates / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013438:Sulfhydryl Compounds / Q000032:analysis; D013482:Superoxide Dismutase / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D001959:Bromates; D008298:Maleates; D013438:Sulfhydryl Compounds; C019536:potassium bromate; D014810:Vitamin E; D000080242:8-Hydroxy-2'-Deoxyguanosine; D013482:Superoxide Dismutase; C014476:diethyl maleate; D003849:Deoxyguanosine; D005978:Glutathione; D003545:Cysteine; D001205:Ascorbic Acid