Protective melatonin effect on oxidative stress induced by okadaic acid into rat brain.

We studied the effect of melatonin on the oxidative changes produced by the intracerebroventricular (i.c.v.) injection of okadaic acid (200 ng/kg BW) in the Wistar rat. The effects of okadaic acid were evaluated as changes in the quantity of lipid peroxides, reduced glutathione content (GSH) and activity of antioxidative enzymes. Okadaic acid caused lipid peroxidation (5.35 +/- 0.47 micro mol/g tissue in the i.c.v. vehicle group versus 10.14 +/- 0.88 micro mol/g tissue in the okadaic acid group, P < 0.001), GSH consumption (0.115 +/- 0.0065 micro mol/g tissue in the i.c.v. vehicle group versus 0.024 +/- 0.0021 micro mol/g tissue, P < 0.001), and a reduction in the activity of GSH-peroxidase, GSH-reductase and GSH-transferase between 60-80%. All these changes were prevented by pre-injection of 4.5 mg melatonin per kg BW 2 hr before okadaic acid. These findings indicate: (i) okadaic acid induces a status of oxidative stress in the brain, characterized by a high level of lipid peroxidation, decreases in GSH content and diminished activities of antioxidative enzymes, and (ii) melatonin prevents the deleterious effects induced by okadaic acid. In conclusion, the results show the ability of melatonin to modify the neural response to okadaic acid with the protective mechanism likely involving the antioxidative processes of melatonin.