Arsenic increased lipid peroxidation in rat tissues by a mechanism independent of glutathione levels.
The role of lipid peroxidation in the mechanism of arsenic toxicity was investigated in female rats pretreated with N-acetylcysteine (NAC, a glutathione [GSH] inducer) or with buthionine sulfoximine (BSO, a GSH depletor). Rats were challenged with sodium arsenite, and sacrificed 1 hr after this treatment. Results showed that arsenic decreased GSH levels and increased lipid peroxidation in liver, kidney, and heart, with a larger effect at 18.2 mg/kg than at 14.8 mg/kg for lipid peroxidation induction. In the liver of rats treated with arsenic, pretreatment with NAC increased the levels of GSH and decreased lipid peroxidation. In kidney and heart, NAC pretreatment protected the tissues against arsenic-induced depletion of GSH levels, but the same degree of protection was not found for lipid peroxidation induction. In its turn, BSO had an additive effect with arsenic in lowering the levels of GSH in the liver and kidney, but an inverse correlation between GSH levels and lipid peroxidation was found only in liver. Arsenic content in tissues of rats pretreated with NAC was lower than in rats treated only with arsenic. In rats with depleted levels of GSH (BSO-pretreated rats), a shift in arsenic tissue distribution was found, with higher levels in skin and lower levels in kidney. A clear tendency for a positive correlation between arsenic concentration and lipid peroxidation levels was found in liver, kidney, and heart.
Ramos
O
O
Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, México.
Carrizales
L
L
Yáñez
L
L
Mejía
J
J
Batres
L
L
Ortíz
D
D
Díaz-Barriga
F
F
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D019328:Buthionine Sulfoximine; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors*; D005978:Glutathione / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D001151:Arsenic; D000111:Acetylcysteine