Regulation of Glutathione Synthesis as The Response to Oxidative and Chemical Stress

Reduced glutathione (GSH) plays an important role in the detoxification of electrophiles and reactive oxygen species (ROS) generated during the biotransformation of some xenobiotics. Many toxicologically important compounds undergo metabolic activation catalyzed by cytochrome P450 (CYP) enzymes, mainly isoenzyme CYP 2E1, to electrophilic reactive intermediates such as: epoxides, quinones, aldehydes and carbocations, and additionally ROS as a by-product. The electrophilicity of the metabolites dictates covalent adduction with nucleophilic sites on nucleic acid or nucleophilic amino acid residues on proteins. Reduced glutathione offers cellular protection since it can react with electrophilic or oxidizing species before they damage critical cellular macromolecules [1,2]. The increase in the cellular GSH level has been reported to serve as an adaptive response to withstand oxidative and chemical stresses that would otherwise have been lethal. The up-regulation of GSH content is achieved mostly through transcriptional mechanism [3,4].