THIORIDAZINE INDUCES LIPID-PEROXIDATION IN MYELIN OF RAT-BRAIN

In this study, the oxidative effect of the commonly used phenothiazine, thioridazine, on brain tissue has been investigated. Thioridazine (0.1 and 0.5%) supplemented in pellet diet (w/w), produced a significant increase (P < 0.001) in levels of myelin lipid peroxide, after 3 weeks of treatment. Besides myelin, there was a 2-fold increase in the mitochondrial lipid peroxides, as a result of treatment with thioridazine. However, these elevated levels of lipid peroxides returned to normal after withdrawal of thioridazine for 2 weeks. Myelin-associated enzyme activities of Na+,K+-ATPase and 5'-nucleotidase became inhibited by 20-25%, but CNPase activity was unaffected. Studies of in vitro lipid peroxidation on purified myelin from untreated rats suggested that extensive lipid peroxidation of myelin in thioridazine-treated rats could underlie inhibition of the myelin enzymes. Morphological studies revealed little or no structural alterations in myelin, produced by thioridazine. These studies suggest that thioridazine induces a reversible lipid peroxidation in myelin, that could result in functional alterations of the myelin-associated enzymes, during use of this drug.