In RXR null mice GST activity and transcription is reduced compared to wild-type mice [11, 12]. In hepatocytes, RXRα deficiency changes the gene expression profiles of the GSTs: it has been reported that basal expression of 13 out of 15 GST genes was altered in hepatocyte-specific RXRα-deficient mice [11], being either down or upregulated. The enzymatic activity of both mitochondrial and cytosolic GSTs is reduced in null mice [12]. Acute ethanol exposure of primary mouse hepatocytes reduces GSH levels and cytosolic GST enzymes activity along with the release of GST into the culture medium. Specific substrates for the mu and pi class demonstrate that ethanol significantly decreases the mu and pi class GST activity by 53% and 13%, respectively. These biochemical changes elicited by ethanol were also accompanied by increased lipid peroxidation and a decreased SAMe to SAH ratio, early biochemical features of ethanol toxicity. Moreover, hepatocytes isolated from RXR KO mice show a decrease of mu and pi class GST activity compared to wild-type mice.
