Vitamins E and C prevent the impairment of retention of an inhibitory avoidance task caused by arginine administration

Abstract

Hyperargininemia is an inherited metabolic disease of urea cycle caused by the deficiency of arginase I activity, resulting in tissue accumulation of arginine (Arg). Patients affected by this disease usually develop spasticity, epilepsy and mental retardation as principal symptoms. Previous studies from our laboratory have showed that acute administration of Arg impairs retention of the inhibitory avoidance task and that l‐NAME (NOS inhibitor) prevents this effect. In the present study, we investigated the effect of chronic treatment with antioxidants (vitamins E and C) on the retrieval of the inhibitory avoidance task in adults rats subjected to experimental model of acute hyperargininemia in order to investigate the participation of oxidative stress on this phenomenon. Sixty‐day‐old‐rats were treated for one week with i.p. injection of saline (0.9%) or vitamins E and C (vit E 40 mg/kg and vit C 100 mg/kg). Twelve hours after the last injection Arg (0.8 g/kg) or an equivalent volume of saline were administered 1 h before training, 1 h before testing or immediately after training sessions. Memory was significantly impaired in Arg‐treated group, whereas the rats chronically treated with vitamins E and C had this effect prevented. Present data strongly indicate that Arg administration impairs memory, an effect probably mediated by oxidative stress since treatment with vitamins E and C prevented amnesia. Assuming the possibility that this might occur in the human condition, reported results may be relevant to explain, at least in part, neurologic dysfunction associated with hyperargininemia.