L-NAME administration prevents the inhibition of nucleotide hydrolysis by rat blood serum subjected to hyperargininemia.

The main objective of the present study was to evaluate the in vivo and in vitro effect of Arg on serum nucleotide hydrolysis. The action of Nomega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, on the effects produced by Arg was also examined. Sixty-day-old rats were treated with a single or a triple (with an interval of 1 h between each injection) intraperitoneal injection of saline (group I), Arg (0.8 g/kg) (group II), L-NAME (2.0 mg/kg or 20 mg/kg) (group III) or Arg (0.8 g/kg) plus L-NAME (2.0 mg/kg or 20 mg/kg) (group IV) and were killed 1 h later. The present results show that a triple Arg administration decreased ATP, ADP and AMP hydrolysis. Simultaneous injection of L-NAME (20 mg/kg) prevented such effects. Arg in vitro did not alter nucleotide hydrolysis. It is suggested that in vivo Arg administration reduces nucleotide hydrolysis in rat serum, probably through nitric oxide or/and peroxynitrite formation.

Effect of hyperprolinemia on acetylcholinesterase and butyrylcholinesterase activities in rat.

We observed here that acute proline (Pro) administration provoked a decrease (32%) of acetylcholinesterase (AChE) activity in cerebral cortex and an increase (22%) of butyrylcholinesterase (BuChE) activity in the serum of 29-day-old rats. In contrast, chronic administration of Pro did not alter AChE or BuChE activities. Furthermore, pretreatment of rats with vitamins E and C combined or alone, N(omega)-nitro-L-arginine methyl ester or melatonin prevented the reduction of AChE activity caused by acute Pro administration, suggesting the participation of oxidative stress in such effects.

In vitro stimulation of oxidative stress in cerebral cortex of rats by the guanidino compounds accumulating in hyperargininemia.

Hyperargininemia is a metabolic disorder biochemically characterized by tissue accumulation of arginine and other guanidino compounds. Convulsions, lethargy and psychomotor delay or cognitive deterioration are predominant clinical features of this disease. Although neurologic symptoms predominate in this disorder, their pathophysiology is still unknown. In the present study we investigated the in vitro effects of arginine, N-acetylarginine, argininic acid and homoarginine on some oxidative stress parameters in rat brain in the hope to identify a possible mechanism for the brain damage in hyperargininemia. Chemiluminescence, total radical-trapping antioxidant potential (TRAP), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were measured in the cerebral cortex of rats in the presence of various concentrations of these compounds. The results showed that all guanidino compounds tested significantly increased chemiluminescence and decreased TRAP at concentrations similar to those observed in the tissue of hyperargininemic patients. Furthermore, these compounds inhibited CAT and GSH-Px activities to varying extents, with GSH-Px activity being more susceptible to their action. In turn, argininic acid inhibited all enzyme activities, and its main action was also directed towards GSH-Px. The results suggest that oxidative stress caused by guanidino compounds may be involved in the brain dysfunction amongst other potential pathophysiological mechanisms observed in hyperargininemia.