Peroxisome Proliferation and Lipid Peroxidation in Rat Liver1 (original) (raw)
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Proliferation of peroxisomes without simultaneous induction of the peroxisomal fatty acid βoxidation
FEBS Letters, 1990
Marked proliferation of rat hepatic peroxisomes is observed after treatment with a new potent hypolipidemic drug BM 15766, as well as after bezafibrate. Whereas the relative specific activity of the peroxisomai fatty acid /?-oxidation system is not affected by BM 15766 it is significantly increased after bezafibrate. This is also confirmed by immunoblot analysis of individual p-oxidation enzymes in highly purified peroxisome fractions.
Lipid composition of liver peroxisomes isolated from untreated and clofibrate-treated mice and rats
Comparative Biochemistry and Physiology Part B: Comparative Biochemistry, 1994
Peroxisomes were isolated from liver tissue of control and clofibrate-treated adult male NMRI mice and Sprague-Dawley rats. Phospholipids, cholesterol, triglycerides and free fatty acids were measured in the peroxisomes. The fatty acid profles of the phosphatidylethanolamine, the phosphatidylcholine, the triglyceride and the free fatty acid fractions were also analyzed. Phosphatidylethanolamine was the dominating phospholipid in peroxisomes from untreated animals. The fatty acid profiles of phosphatidylethanolamine, free fatty acids and triglycerides were similar for untreated mice and rats but differences between the species were observed in the pattern derived from phosphatidylcholine. Phosphatidylcholine was the most abundant phospholipid after clofibrate treatment. Cloflbrate treatment caused an increase in the concentrations of phospholipids and unsaturated long-chain fatty acids and a decrease in the concentrations of triglycerides, free fatty acids, cholesterol and shorter saturated fatty acids.
Peroxisomes and Hepatotoxicity
Comparative Haematology International, 1995
Peroxisomes are ubiquitous organelles of eukaryotic cells and are present in significant amounts in hepatic liver cells. Peroxisomal enzymes contribute to several metabolic pathways including fatty acid, purine and amino acid catabolism or bile acid synthesis. The peroxisomal oxidative reactions produce hydrogen peroxide, mostly degraded by catalase which prevents oxidative stress. Moreover, peroxisomes are involved in arylderivative drug detoxification through its epoxide hydrolase activity. In rodents the exposure of cells to xenobiotic compounds such as fibrates, phthalates/adipates and chlorophenoxyacetic acid derivatives, which are used as hypolipaemic drugs, plasticizers and pesticides respectively, lead to a liver mass increase and to a high peroxisome proliferation. This latter event is due to a strong genetic activation triggered by the PPAR (peroxisome proliferator activated nuclear receptor). Human contrasts with rodent since there is no, or little, effect of the above cited compounds. In contrast, the defect of single or multiple peroxisomal functions caused by genetic disorders lead to an increase of very long chain fatty acid level, which is toxic, especially for brain and kidney. The liver response to xenobiotics of the peroxisome proliferator class may be modulated by * Originally presented at the Second European Comparative Clinical Pathology Conference, Dijon.
Influence of lipid peroxidation on lipoprotein secretion by isolated hepatocytes
Lipids, 1981
Isolated rat liver cells have been exposed to 3 different lipid peroxidation-inducing agents, CC14, FeC13 and cumene hydroperoxide, and the rates of malonaldehyde production and of lipoprotein secretion have been compared. Results indicate that it is possible to induce a high degree of lipid peroxidation without inducing strong changes in lipoprotein secretion. Only in CC14-poisoned hepatocytes is lipoprotein secretion strongly impaired. In this experimental condition, the effect of free radical scavengers, or inhibitors of lipid peroxidation, has been studied; the degree of covalent binding of CCI 4 metabolites to hepatocyte proteins, as well as the behavior of both lipid peroxidation and lipoprotein secretion, have been evaluated. Promethazine and propyl gallate prevented malonaldehyde production, but neither agent reduced covalent binding nor improved secretion. Menadione, on the contrary, besides inhibiting malonaldehyde production, decreased covalent binding and protected against the impairment of secretion. These data lead to the conclusion that covalent binding ofCCl 4 metabolites, rather than lipid peroxidation products, accounts for the derangement of lipoprotein secretion in CCI,-poisoned liver cells.
SUBCELLULAR FRACTIONATION STUDIES ON THE ORGANIZATION OF FATTY ACID OXIDATION BY LIVER PEROXISOMES
Annals of the New York Academy of Sciences, 1982
The presence in peroxisomes of the enzymes required for the @-oxidation of fatty acyl-CoA derivatives is now clearly established for a wide variety of tissues and species, including humans.'6 Yet the mechanisms involved in the in vivo regulation of the pathway and its overall rate of activity in intact tissues, are not known. It has been claimed from studies with isolated hepatocytes that only a minor fraction of the peroxisomal activity detected in homogenates, under optimal assay conditions, is expressed in intact ~e 1 l s . l~
Pediatric Research, 1987
Control mice were fed on a standard animal food. Treated animals were fed on a diet obtained by mixi ng the powdered 1200 animal food with either 0.1 % clofibric acid, 0.1 % POCA, 20% oleate, and 0.1 or 0.5% chlorpro mazine. Supported by Grants of the Belgian NFWO, FN RS, and SPPS, by G rant 84/90-74 of the "Action de Recherche Concertce des Services du Premier Ministre", U.S. Public Health Services G rant AM9235, European Communities Twinning Research Program, and Grant 3.007 1.83 of the Belgian FGWO. J.Y. is Charge of the Belgian FN RS. 748 Clofibric acid (2-5p(chlorophenoxy)-2-methylpropionic acid), trifluoperazine, hom ovanillic acid, and peroxidase type II were purchased from Sigma Chemical Co. (St. MO). The CoA derivatives of palmitic, lauric, octanoic, hexanoic, and acetic