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.
Dhaunsi
G S
GS
Department of Pediatrics, Medical University of South Carolina, Charleston 29425.
Singh
B
B
Singh
A K
AK
Kirschner
D A
DA
Singh
I
I
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D015720:5'-Nucleotidase / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D004032:Diet; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013881:Thioridazine / Q000494:pharmacology*; D014961:X-Ray Diffraction
D015720:5'-Nucleotidase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D000254:Sodium-Potassium-Exchanging ATPase; D013881:Thioridazine