Potential preventive effects of coenzyme Q and creatine supplementation on brain energy metabolism in rats exposed to chronic cerebral hypoperfusion

It is well known that both oxidative stress and mitochondrial dysfunction play important roles in animal models of brain ischemia. This study was undertaken to test whether oral supplementation of coenzyme Q10 (ubiquinone) or creatine citrate could protect brain ischemia-induced mitochondrial damage in the rats. Brain ischemia was induced for 50 min. with three-vessel occlusion (3-VO). Coenzyme Q10 was administered for 30 days before the ischemic event, and coenzyme Q10 or creatine citrate was administered for 30 days postischemia. Moreover, the concentrations of coenzyme Q10 and α-tocopherols as well as the formation of thiobarbituric acid reactive substances (TBARS) were measured in brain mitochondria and in plasma. Transient hypoperfusion revealed significant impairment in brain energy metabolism as detected by mitochondrial oxidative phosphorylation, decreased concentrations of brain and plasma endogenous antioxidants, and increased formation of TBARS in plasma. When compared with the ischemic group, supplementation of coenzyme Q10 was ineffective as a preventive agent. However, the positive effect of therapeutic coenzyme Q10 supplementation was supported by the oxygen consumption values (p < 0.05) and ATP production (p < 0.05) in brain mitochondria, by increased concentration of coenzyme Q9 (p < 0.05) and α-tocopherol (p < 0.05) in brain mitochondria, and by increased concentration of α-tocopherol (p < 0.05) and γ-tocopherol in plasma. This suggests that coenzyme Q10 therapy involves resistance to oxidative stress and improved brain bioenergetics, when supplemented during reperfusion after the chronic hypoperfusion induced ischemic brain injury.