thiobarbituric-acid and Nerve-Degeneration

Increasing evidence suggests that some of the neurobiological and neurotoxic actions of apomorphine and other dopamine receptor agonists might be mediated by their oxidation derivatives. The aim of the present study was to evaluate the effects of apomorphine and its oxidation derivative, 8-oxo-apomorphine-semiquinone (8-OASQ), on oxidative stress parameters and antioxidant enzyme activity. Adult male CF-1 mice were treated with a systemic injection of apomorphine (0.4, 4.0 or 40.0 mg/kg) or 8-OASQ (0.4, 4.0 or 40.0 mg/kg). Animals were sacrificed by decapitation 24 h after treatment, and the forebrains were collected for analysis of thiobarbituric acid reactive species, protein carbonyls, the total radical-trapping antioxidant parameter, catalase and superoxide dismutase. These treatments did not induce lipid peroxidation at any dose tested. In contrast, apomorphine induced an increase in protein carbonylation and a decrease in total radical-trapping antioxidant parameter at all doses tested. 8-OASQ induced an increase in protein carbonylation and a decrease in total radical-trapping antioxidant parameter only at the higher dose tested. All apomorphine doses tested induced an increase in catalase, but not superoxide dismutase activities. In contrast, 8-OASQ induced a dose-dependent increase in CAT activity. The results suggest that apomorphine and its oxidation product, 8-OASQ, induce differential effects on CNS oxidative parameters.

Topics: Animals; Apomorphine; Brain; Catalase; Dopamine Agonists; Dose-Response Relationship, Drug; Free Radicals; Male; Mice; Nerve Degeneration; Neurons; Oxidative Stress; Quinones; Reactive Oxygen Species; Superoxide Dismutase; Thiobarbiturates

Topics: Animals; Corpus Striatum; Culture Techniques; Dopamine; Electron Spin Resonance Spectroscopy; Free Radicals; Hydroxides; Hydroxyl Radical; Levodopa; Male; Mice; Mice, Inbred ICR; Microscopy, Electron; Nerve Degeneration; Receptors, Dopamine; Subcellular Fractions; Substantia Nigra; Superoxides; Thiobarbiturates