Folic acid pretreatment prevents the reduction of Na+,K+-ATPase and butyrylcholinesterase activities in rats subjected to acute hyperhomocysteinemia

The main objective of the present study was to evaluate the effect of folic acid pretreatment on parietal cortex Na+,K+-ATPase and serum butyrylcholinesterase activities in rats subjected to acute hyperhomocysteinemia. Animals were pretreated daily with an intraperitoneal injection of folic acid (5 mg/kg) or saline from the 22th to the 28th day of age. Twelve hours after the last injection of folic acid or saline, the rats received a single subcutaneous injection of homocysteine (0.6 μmol/g of weight body) or saline and were killed 1 h later. Serum was collected and the brain was quickly removed and parietal cortex dissected. Results showed that acute homocysteine administration significantly decreased the activities of Na+,K+-ATPase and butyrylcholinesterase on parietal cortex and serum, respectively. Furthermore, folic acid pretreatment totally prevented these inhibitory effects. We also evaluated the effect of acute homocysteine administration on some parameters of oxidative stress, namely thiobarbituric acid-reactive substances and total thiol content in parietal cortex of rats. No alteration of these parameters were observed in parietal cortex of homocysteinemic animals, indicating that these oxidative stress parameters were probably not responsible for the reduction of Na+,K+-ATPase and butyrylcholinesterase activities. The presented results confirm previous findings that acute hyperhomocysteinemia produces an inhibition of Na+,K+-ATPase and butyrylcholinesterase activities and that pretreatment with folic acid prevents such effects. Assuming that homocysteine might also reduce the activities of these enzymes in human beings, our results support a new potential therapeutic strategy based on folic acid supplementation to prevent the neurological damage found in hyperhomocysteinemia.