Long-term effects of hypolipidemic peroxisome proliferator administration on hepatic hydrogen peroxide metabolism in rats

Publisher Website
Google Scholar
Abstract
The effects of prolonged dietary administration of proxisome proliferators, such as clofibrate, bezafibrate and di(2-ethylhexyl)phthalate (DEHP), on hepatic hydrogen peroxide (H2O2) level and on hepatic activities of the enzymes relating to H2O2 metabolism were examined. Male rats were treated for 79 weeks with the above three peroxisome proliferators. The activities of the proxisomal β-oxidation and catalase were increased 8- to 20-fold and 2- to 3-fold, respectively, after 2 or 4 weeks of treatment with these peroxisome proliferators. However at 79 weeks the proxisomal β-oxidation activity was 3–8 times that of control. The level of catalase activity was kept at ∼2-fold even after prolonged treatment of proxisome proliferators. Although the activities of glutathione proxidase (GSH-Px) and glutathione S-transferase (GST) were decreased 50–60% at 4–12 weeks by the treatment with proxisome proliferators, from 20 to 79 weeks those activities approached control levels in the case of clofibrate and bezafibrate but not DEHP-fed rats; GSW-Px and GST activities were kept at ∼40% those of control. However hepatic capacities of H2O2-degrading enzymes, catalase and GSH-Px, apparently exceeded the H2O2-generating levels obtained on the basis of peroxisomal β-oxidation activities in the livers of control and treated rats throughout the experimental period. The hepatic H2O2 levels increased only slightly but this increase did not correspond to changes in proxisomal β-oxidation. Our results suggest that a large part of H2O2 produced by peroxisomal β-oxidation could be rapidly scavenged by catalase and GSH-Px in the liver of rats treated with proxisome proliferators.