Chemiluminescence and antioxidant levels during peroxisome proliferation by fenofibrate

Abstract

Fenofibrate, the hypolipidemic drug and peroxisome proliferator, was given to mice (0.23% w/w in the diet) during 1-3 weeks and H2O2 and TBARS steady state concentrations, liver chemiluminescence and antioxidant levels were measured. Administration of fenofibrate during 2 weeks induced an increase of 89% in H2O2 steady state concentration. Spontaneous chemiluminescence was decreased by 57% during fenofibrate treatment, while no significant effect was observed on TBARS concentration. Hydroperoxide-initiated chemiluminescence was decreased by 56% after 15 days of fenofibrate treatment, probably due to an increase in endogenous antioxidant levels. Total and oxidized glutathione increased gradually after fenofibrate administration, obtaining maximal increases of 67% and 58% respectively, after 22 days of treatment. An increase of 55% was found in ubiquinol levels in treated mice, as compared with the controls. alpha-tocopherol content was decreased by 51% in the liver of fenofibrate-treated mice. According to our findings, the high rate of H2O2 production associated with peroxisome proliferation, would not lead to an increase in lipid peroxidation. This can be explained by the presence of high levels of ubiquinols, which act as an antioxidant. The increased production of H2O2, would lead to DNA damage directly, and not through lipid peroxidation processes.

Effects of diet-induced obesity on protein expression in insulin signaling pathways of skeletal muscle in male Wistar rats

“…Reactive oxygen species are some of the end products of beta oxidation of fatty acids which may have a major role in increasing expression and phosphorylation of PKC-β 25,26. Furthermore, various reports have indicated that fenofibrate is associated with increased production and availability of reactive oxygen species,27–29 further underlined by the increased PKC-β levels seen in the fenofibrate-treated group in our study. Hence, our results indicate that diet-induced obesity can cause increased expression of PKC-β in skeletal muscle, which augments systemic insulin resistance.…”

Fenofibrate decreases radiation sensitivity via peroxisome proliferator-activated receptor α-mediated superoxide dismutase induction in HeLa cells

“…The PPRE, the binding site for PPAR, has been recently identified in the promoter area for the catalase and SOD genes, and therefore, catalase and SOD have been identified as the target enzymes of PPARα [25,26]. Previous studies have demonstrated that peroxisome proliferators like fibrates led to increases in the activity of peroxisomal oxidases, with a concomitant increase in antioxidant enzymes, in mainly catalase [10-16]. Among the synthetic peroxisome proliferators, the largest group consists of the amphipathic carboxylates, such as Wy-14643, benzafibrate, ciprofibrate, fenofibrate, and clofibric acid.…”

Clofibrate pretreatment in mice confers resistance against hepatic lipid peroxidation

“…Our observation of a resistance to TBARS formation in liver homogenates from CL-pretreated mice thus suggests an increased antioxidant status and concurs with similar observations from other laboratories who have studied the effects of various peroxisome proliferators on pro-oxidant-induced lipid peroxidation. For example, hepatic microsomes from ciprofibrate-pretreated rats were found to generate less TBARS upon incubation with cumene hydroperoxide [41]; pretreatment with CL diminished TBARS yields in rat liver homogenates induced by haloacetic acids [42]; while hydroperoxideinitiated chemiluminescence was diminished in liver homogenates by prior exposure of mice to fenofibrate [4]. Along similar lines, ciprofibrate pretreatment abolished malondialdehyde formation in the livers of catalase-overexpressing transgenic mice [43].…”

“…The increase in peroxisome numbers caused by these chemicals has many cellular consequences, among the most significant of which is an overproduction of hydrogen peroxide (H 2 O 2 ) [4]. This is thought to occur because the induction of peroxisomal fatty acid b-oxidation (a H 2 O 2 -producing pathway) exceeds that of catalase, a peroxisomal H 2 O 2 -catabolizing pathway [5][6][7].…”