Glutathione S transferases constitute a family of enzymes in
Glutathione-S-transferases constitute a family of enzymes involved in the detoxification of xenobiotics, signalling cascades and serving as ligandins or/and catalyzing the conjugation of various chemicals and drugs . The present finding indicates significant increase in GST activity in the brain. This is corroborated by Mourad , who reports an increase in GST activity in the liver tissue that could be a response of the organ to the oxidative stress induced by the methanol metabolized from aspartame and possibly the induction of enzyme synthesis by aspartame. Therefore, the present persistent decrease in GSH content is likely to be reasonable due to the concomitant increase in the GST activity, as the GSH acts as a substrate of the enzymatic reaction of GST . Estimating the activities of serum marker enzymes, like γ-GT, makes assessment of liver function. It has been reported that excess alcohol consumption has been linked with altered liver metabolism and liver damage with leakage of cytoplasmic liver enzyme γ GT into blood . The enhanced activities of these serum marker enzymes was due to methanol intoxication, altered oxidant/antioxidant balance and surface charge density, which caused leakage of ALT and AST . It is certainly possible that the enhanced activities of γ-GT in aspartame treated MTX observed in this study are due to methanol, the by-product of aspartame metabolism, whereas there were no changes between control and MTX treated groups. γ-GT is a microsomal enzyme present in hepatocytes and its primary role is to metabolize extracellular GSH, allowing for precursor of Spadin to be assimilated and reutilized for intracellular GSH synthesis. An increase in serum γ-GT is a defence mechanism reflecting the induction of cellular γ-GT, when there is oxidative stress . Rajamani et al.  reported that methanol-induced increased production of free radicals and increased oxidative damage to proteins in distinct brain regions, retina and optic nerve. This corroborates with increase protein carbonyl levels in cerebral cortex, cerebellum, midbrain, pons-medulla, hippocampus and hypothalamus when compared to control and MTX alone group. Free radicals formed during the methanol oxidation can also cause the formation of protein peroxides. These changes may result in denaturation, aggregation and fragmentation of proteins, altering physicochemical properties and potentially losing of enzymatic activities . The detection and measurement of LPO is the evidence most frequently cited in support of the involvement of free radicals in toxicology and human diseases . Huang et al.  reported depletion of tissue. GSH is one of the major factors that permit lipid peroxidation and subsequent tissue damage. LPO in cellular membranes damages polyunsaturated fatty acids tending to reduce membrane fluidity, which is essential for proper functioning of the cell. A marked increase in LPO substantiates the generation of free radicals following aspartame consumption. Oxidative stress contributes to the pathophysiology of liver and renal damage. Histopathological examination of the livers and kidney when aspartame-administered to rats revealed marked degenerative changes in aspartame treated MTX compared to control and MTX alone treated animals. Reactive oxygen species, which prevail due to decreased antioxidant defense mechanism, may stimulate the release and formation of various inflammatory chemokines. Chemokines are involved in the migration of leukocytes into liver during alcohol intoxication . Chronic intoxication selectively enhances chemokine release by Kupferr cells and hepatic sinusoidal cells and migration of inflammatory cells to liver. Significant amount of neutrophil infiltration was noted in the liver parenchyma of aspartame-administered group along with notable changes in nuclear condensations and microvacuole formation in the cytoplasm. Methanol-induced free radicals and an imbalanced antioxidant system may damage the kidney functions and probably contribute to the increased serum urea and creatinine concentrations seen in this study . Pathophysiology study in the renal cortex showed marked glomerular damages, including the loss of normal architecture and reduction in their normal sizes. The epithelium of the proximal and distal convoluted tubules showed peeled off brush borders from the surface. Thus, the result from the foregoing study indicates that a decrease in the antioxidant status is one of the main factors contributing to methanol intoxication in brain and liver.