ANTIOXIDANT DEFENSE IN RAT-BRAIN AFTER CHRONIC TREATMENT WITH ANORECTIC DRUGS

Mazindol hydroxy-5-p-chlorophenyl-2,3-dihydro-5H-isoindole) although n ot chemically related to the phenylethylamine group, shows a pharmacol ogical profile similar to that of amphetamines. In rats these anorecti c drugs enhance dopamine (DA) turnover, which is the mechanism that ca uses anorexia. It has been hypothesized that amphetamine causes a long -lasting depletion of DA, a decrease of dopaminergic transport pumps a nd nerve terminal degeneration increasing. These actions provide a cel lular environment encouraging the autoxidation of DA that may lead to lipid peroxidation and neuronal damage. Considering that both drugs ma y cause neuronal damage by oxidative mechanisms, this study was conduc ted to investigate the action of mazindol and methamphetamine on brain cell antioxidant defense system and to investigate whether animal age is important in the antioxidant response to chronic anorectic adminis tration. The activity of superoxide dismutase (SOD), catalase (CAT) an d glutathione peroxidase (GPx), as well as the total glutathione (GSH) content in brains of rats, were measured. The animals (2 groups with 5 and 18 months old) were treated for 5 months (i.p.) with mazindol (1 0 mg/kg body weight/day), methamphetamine (2.5 mg/kg body weight/day) or saline. The results obtained showed no differences between SOD, CAT , GPx activities and GSH content in the brain of animals treated with saline compared with both drugs, either in 10-month or 23-month groups . On the other hand, brain total GSH content of old animals was found to be lower than that from young ones, independent of the treatment. S OD activity was found to be increased, CAT unchanged and GPx decreased , in the brain of old animals, treated with both drugs or saline. Thes e findings led us to conclude that the chronic administration of mazin dol and methamphetamine have no effects on the antioxidant systems stu died either in young (10 months) or in old (23 months) rats.