In vitro effect of methanol on folate-deficient rat hepatocytes

Abstract

Methanol is primarily metabolized by oxidation to formaldehyde and then to formic acid. These processes are accompanied by formation of superoxide anion and hydrogen peroxide. This paper reports the in vitro antioxidant effect of vitamin E on isolated hepatocytes of folic acid deficient rats rendered so as to emulate a human hepatocyte model. These hepatocytes were treated with 320 μmol of methanol per million cells and incubated for 30 min. The microsomal fraction of these hepatocytes showed a decreased level of superoxide dismutase (SOD), with increase in lipid peroxidation (LPO) shown by increase in recorded levels of malondialdehyde (MDA). Catalase activity was shown to be increased. Levels of reduced glutathione (GSH) were decreased and the activity of glutathione peroxidase (GSH-Px) and of glutathione reductase (GSSG-R) were not altered. The hepatocytes of folate deficient rats pretreated with vitamin E, when subjected to methanol treatment, showed no significant change in SOD levels and a significant decrease in MDA levels. The catalase activity in this group of animals showed a highly significant decrease. These animals had normal levels of GSH, while a significant fall in GSH-Px and GSSG-R levels were observed. These results suggest that Vitamin E exerts a protective effect on hepatocytes by acting as a free radical scavenger, proving its usefulness in treating methanol toxicity.