Neuroprotective Effect of Grape Seed and Skin Extract on Lithium-Induced Oxidative Stress in Healthy Rat Brain

Lithium is used in the therapy of various psychoses based on its antidepressant and mood stabilizing properties. However it also exerted toxic side effects in long standing treatment. We studied the effect of lithium on brain oxidative stress status into healthy rat as well as the putative protection afforded by grape seed and skin extract, used as an antioxidant and anti-inflammatory agent. Lithium generated an oxidative stress characterized by increased lipoperoxidation and carbonylation, decreased antioxidant enzyme activities as catalase, superoxide dismutase and glutathione peroxidase. Furthermore lithium altered transition metals distribution and associated enzyme activities, increased intracellular mediators as H2O2, free iron, calcium, magnesium and calpain activity but decreased acetylcholinesterase activity. Lithium also disturbed brain lipidemia as evidenced by high triglyceride and cholesterol and low lipase activity. Almost all deleterious effects of lithium were normalized by grape seed and skin extract especially at the therapeutic doses of lithium. Grape seed and skin extract could be proposed as an efficient neuroprotectant to mitigate the adverse side effects of lithium.