Hyperargininemia is a metabolic disorder biochemically characterized by tissue accumulating 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 initially investigated the in vitro effect of
arginine,
homoarginine, N-acetylarginine and
argininic acid on
acetylcholinesterase and
butyrylcholinesterase in hippocampus and serum of 15-, 30- and 60-day-old rats. Results showed that
arginine in vitro significantly decreased
acetylcholinesterase activity in hippocampus of 15-day-old rats and increased this
enzyme activity in hippocampus of 60-day-old rats,
homoarginine and N-acetylarginine significantly increased
acetylcholinesterase activity both in hippocampus of 15- and 30-day-old rats. On the other hand,
butyrylcholinesterase was inhibited by
homoarginine in serum of 15-day-old rats. The influence of the
antioxidants trolox and
ascorbic acid on the effects elicited by
arginine,
homoarginine and N-acetylarginine was also studied. Results showed that these
antioxidants were able to prevent the alteration on
acetylcholinesterase and
butyrylcholinesterase activities caused by
guanidine compounds studied, suggesting that alterations on these
cholinesterases were probably mediated by
free radicals. It is presumed that these results might be associated, at least in part, with the neuronal dysfunction of patients affected by
hyperargininemia.