Brain Na+,K(+)-ATPase inhibition induced by arginine administration is prevented by vitamins E and C.

Hyperargininemia is a metabolic disorder caused by deficiency of arginase activity resulting in tissue accumulation of arginine and neurological dysfunction. We have previously demonstrated that arginine induces oxidative stress and decreases Na+,K(+)-ATPase in rat midbrain. In the present study we investigated the action of vitamins E and C on the inhibition of Na+,K(+)-ATPase provoked by arginine in the midbrain of 60-day-old rats. Animals were pretreated for 1 week with daily IP administration of saline (control) or vitamins E (40 mg/kg) and C (100 mg/kg). Twelve h after the last injection, animals received one injection of arginine (0.8 micromol/g of body weight) or saline. Chemiluminescence was significantly increased, whereas total antioxidant capacity and Na+,K(+)-ATPase activity were significantly decreased. Furthermore, treatment with vitamins E and C prevented these effects. If these effects also occur in the human condition, it is possible that antioxidant administration might slow the progression of neurodegeneration in this disorder.