Decreased nitric oxide production in the rat brain after chronic arsenic exposure.
Chronic arsenic exposure is associated with nervous system damage, vascular disease, hepatic and renal damage as well as different types of cancer. Alterations of nitric oxide (NO) in the periphery have been detected after arsenic exposure, and we explored here NO production in the brain. Female Wistar rats were exposed to arsenite in drinking water (4-5 mg/kg/day) from gestation, lactation and until 4 months of age. NOS activity, NO metabolites content, reactive oxygen species production (ROS) and lipid peroxidation (LPx) were determined in vitro in the striatum, and NO production was estimated in vivo measuring citrulline by microdialysis. Exposed animals showed a significantly lower response to NMDA receptor stimulation, reduction of NOS activity and decreased levels of nitrites and nitrates in striatum. These markers of NO function were accompanied by significantly higher levels of LPx and ROS production. These results provide evidence of NO dysfunction in the rat brain associated with arsenic exposure.
Zarazúa
Sergio
S
Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, Av. V. Carranza 2405 Col. Los Filtros, 78210 San Luis Potosí S.L.P., Mexico.
Pérez-Severiano
Francisca
F
Delgado
Juan Manuel
JM
Martínez
Luz M
LM
Ortiz-Pérez
Deogracias
D
Jiménez-Capdeville
María E
ME
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D020261:Arsenic Poisoning; D018053:Arsenites / Q000008:administration & dosage / Q000494:pharmacology; D001835:Body Weight; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D017670:Sodium Compounds / Q000008:administration & dosage / Q000494:pharmacology
D018053:Arsenites; D004791:Enzyme Inhibitors; D017670:Sodium Compounds; D009569:Nitric Oxide; C017947:sodium arsenite; D019001:Nitric Oxide Synthase; D001151:Arsenic