title: Diazepam induced early oxidative changes at the subcellular level in rat brain.
abstract: Studies were conducted to ascertain any involvement of free radical mediated prooxidative processes in different brain regions following diazepam administration. A significant decrease in TBA reactive substance formation was observed in cerebral cortex, cerebellum and brain stem regions after single doses of 1.5, 3 and 6 mg/kg b.wt. For further studies rats were given diazepam (i.p.) at 3 mg/kg body weight dose and sacrificed after 1 h to follow changes in the pro/antioxidant status. An enhancement in the TBARS formation was found in the mitochondrial fractions from cerebral cortex and brain stem. This effect was highest in brain stem being 107% as compared to controls. In the post mitochondrial fraction, cerebellum showed 49% enhancement whereas decreased formation of thiobarbituric acid reactive substances was observed in cerebral cortex and brain stem. Isozymes of superoxide dismutase showed a decrease in activity which was region dependent. Even though, total thiols were not significantly altered, free thiols showed depletion in cerebellum (39.8%) and brain stem (50%). Glutathione reductase activity was also decreased in cerebellum and brain stem. The results indicate that a single dose of diazepam causes free radical mediated changes and the modulatory response of antioxidant defences appears to be region specific.
authors.affiliation: Ecotoxicology Division, Industrial Toxicology Research Centre, M.G. Marg, Lucknow, India.
authors.forename: S
authors.initials: S
authors.lastname: Musavi
authors.forename: P
authors.initials: P
authors.lastname: Kakkar
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D005609:Free Radicals; D005980:Glutathione Reductase / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D002491:Central Nervous System Agents; D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D005980:Glutathione Reductase; D003975:Diazepam