RELATIONSHIP BETWEEN PEROXISOME-PROLIFERATING SULFUR-SUBSTITUTED FATTY-ACID ANALOGS, HEPATIC LIPID-PEROXIDATION AND HYDROGEN-PEROXIDE METABOLISM

The effect of the administration of three peroxisome-proliferating sulfur-substituted fatty acid analogs on hepatic antioxidant status and lipid peroxidation was studied in rats. After 14 days of treatment, the ratio of induction of peroxisomal fatty acyl-CoA oxidase to catalase was 4.2 and 3.5 in rats treated with 1, 10 bis-(carboxymethylthio)decane (BCMTD) and 1-mono (carboxymethylthio)tetradecane (CMTTD), respectively, while the corresponding ratio was 1.3 in 1-mono (carboxyethylthio)tetradecane (CETTD)-treated rats. As compared to the controls an increase in hepatic hydrogen peroxide content was noted in BCMTD- and CMTTD-treated rats, but not CETTD-treated rats. Hepatic lipid peroxidation was increased in all the three treatment groups in a manner not related to the potency of the compounds to induce the peroxisomal hydrogen peroxide metabolizing enzymes. Hepatic glutathione content increased while the activities of its associated enzymes such as glutathione transferase, glutathione peroxidase and glutathione reductase decreased in all the treated rats. Taken together, our data show a relationship between the levels of hydrogen peroxide and lipid peroxidation in rat livers treated with BCMTD and CMTTD. However, increased hepatic lipid peroxidation in CETTD-treated rats cannot be accounted for by the changes in the peroxisomal enzymes.