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J.Health Sci., 52(6), 730-737, 2006

Cerebral Oxidative Stress and Mitochondrial Dysfunction in Oxonate-Induced Hyperuricemic Mice

Satoshi Watanabe,*, a Fumiko Kiyama,a Aika Sakamaki,a Tadashi Yoshida,b and Tetsuya Fukuia

aDepartment of Health Chemistry, and bDepartment of Pathophysiology, Faculty of Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo 142-8501, Japan

Relation between blood uric acid levels and brain cell functions were examined using potassium oxonate-induced hyperuricemic mice and allopurinol-induced hypouricemic mice. In hyperuricemic mice and hypouricemic mice, erythrocyte catalase activity was significantly lower and higher, respectively, than that in the control group. No significant change of superoxide dismutase (SOD) activity or glutathione peroxidase activity was observed in either group. Cerebral lipid peroxide levels expressed as thiobarbituric acid reactive substances (TBARS) were significantly higher in hyperuricemic mice, and cerebral mitochondrial ATP synthesis and manganese-containing SOD (Mn-SOD) activity were significantly diminished in the same mice. In hypouricemic mice, no significant change was observed for TBARS levels, mitochondrial ATP synthesis and Mn-SOD activity. Then significant negative correlation between erythrocyte catalase activity and cerebral TBARS levels, and significant positive correlation between catalase activity and mitochondrial ATP synthesis were confirmed. Furthermore, when mouse erythrocytes were treated with uric acid, their catalase activities were particularly diminished. These results suggest that the reduction of erythrocyte catalase activity resulted from the elevation of blood uric acid levels is a major cause of cerebral oxidative stress and mitochondrial dysfunction in hyperuricemic mice. Therefore, it is possible that hyperuricemia and gout are risk factors of cerebral disorders.