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

Abstract

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 micromol/g of weight body) or saline and were killed 1h 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.

Hyperhomocysteinemia reduces glutamate uptake in parietal cortex of rats

“…In this situation, GLAST and GLT‐1, which are dependent of sodium‐gradient, could reverse the direction of glutamate transport, resulting in accumulation of extracellular glutamate (Danbolt, 2001; Maragakis and Rothstein, 2004; Sheldon and Robinson, 2007; Nicholls, 2008). Consistent with these findings, we previous showed that Hcy chronic and acute administrations inhibited Na + , K + ‐ATPase activity in plasmatic membranes prepared from parietal cortex of rats (Matté et al, 2004, 2006, 2007), as well as in hippocampus (Streck et al, 2002; Wyse et al, 2002). Contributing with this hypothesis, a similar effect has been reported for ischemia (Rossi et al, 2000; Camacho and Massieu, 2006; Sheldon and Robinson, 2007), and some neurodegenerative diseases (Greenamyre et al, 1999; Higgins et al, 1999), that have been related to hyperhomocysteinemia (Mattson et al, 2002; Obeid et al, 2007).…”

“…We also evaluated the immunocontent of GLAST and GLT‐1 in parietal cortex of rats subjected to chronic hyperhomocysteinemia. Parietal cortex was selected because patients presenting hyperhomocysteinemia exhibit cortical atrophy (Sachdev, 2005), moreover we have shown that Hcy elicits several neurotoxic effects in this cerebral structure (Matté et al, 2006, 2007, 2009).…”

Homocysteine Induces Hypophosphorylation of Intermediate Filaments and Reorganization of Actin Cytoskeleton in C6 Glioma Cells

“…Data were statistically analyzed by one-way ANOVA. Representative immunological reactions are shown alterations caused by Hcy (Matte et al 2006;Stefanello et al 2005;Tagliari et al 2006), we also tested whether the effect of Hcy on the formation of filopodia in C6-glioma cells could be prevented by these compounds. Cells were treated with folic acid (5 lM), trolox (80 lM), and ascorbic acid (1 mM) in the absence (controls) or presence of 100 or 500 lM Hcy for 4 h. We observed that they totally prevented the 100 lM Hcy-induced filopodia formation, since the number of cells containing abundant and long filopodia attained levels similar to controls (Fig.…”

Synthesis, Spectroscopic and Thermal Characterization of Copper(II) and Iron(III) Complexes of Folic Acid and Their Absorption Efficiency in the Blood

“…It has been shown that folic acid supplementation can significantly reduce the risk of these disorders [6–14]. Folates are the key cofactors in one-carbon metabolism.…”