Effect of hypermethioninemia on some parameters of oxidative stress and on Na(+),K (+)-ATPase activity in hippocampus of rats.

In the present study we investigated the effect of chronic administration of methionine, a metabolite accumulated in many inherited pathological conditions such as methionine adenosyltransferase deficiency and homocystinuria, on some parameters of oxidative stress, namely thiobarbituric acid reactive substances (TBARS), catalase activity and total thiol content, as well as on Na(+),K(+)-ATPase activity in rat hippocampus. For chronic treatment, rats received subcutaneous injections of methionine (1.34-2.68 mumol/g of body weight), twice a day, from the 6th to the 28th day of age and controls received saline. Animals were killed 12 h after the last injection. Results showed that chronic hypermethioninemia significantly increased TBARS, decreased Na(+),K(+)-ATPase activity but did not alter catalase and total thiol content. Since chronic hypermethioninemia altered TBARS and Na(+),K(+)-ATPase activity at 12 h after methionine administration, we also investigated the effect of acute administration of this amino acid on the same parameters studied after chronic methionine administration. For acute treatment,29-day-old rats received one single injection of methionine (2.68 mumol/g of body weight) or saline and were killed 1, 3 or 12 h later. Results showed that rats subjected to acute hypermethioninemia presented a reduction of Na(+),K(+)-ATPase activity and an increase in TBARS when the animals were killed at 3 and 12 h, but not at 1 h, after methionine administration. These data indicate that hypermethioninemia increases lipid peroxidation which may, at least partially, explain the effect of methionine on the reduction in Na(+),K(+)-ATPase activity. If confirmed in human beings, our findings could suggest that the induction of oxidative stress and the inhibition of Na(+),K(+)-ATPase activity caused by methionine might contribute to the neurophysiopathology observed in patients with severe hypermethioninemia.