Effects of clofibric and beclobric acid in rat and monkey hepatocyte primary culture: influence on peroxisomal and mitochondrial beta-oxidation and the activity of catalase, glutathione S-transferase and glutathione peroxidase.
The effect of hypolipidaemic compounds on peroxisomal fatty acid beta-oxidation and on peroxisome morphology in the liver differs widely between rodent and primate species. We studied the relative importance of peroxisomal and mitochondrial beta-oxidation of palmitate in primary cultures of hepatocytes isolated from rat and monkey liver in the absence or presence of clofibric acid or beclobric acid. It was demonstrated that it is possible to differentiate between peroxisomal and mitochondrial beta-oxidation activities in intact cells. Overall beta-oxidation of palmitate was ca. 30% higher in rat hepatocytes than in monkey liver cells. In both monkey and rat cell cultures the mitochondrial component was over 90% of the total palmitate beta-oxidation. In rat hepatocyte culture clofibric acid and beclobric acid caused a 5- to 8-fold stimulation of peroxisomal beta-oxidation, while in monkey cells this activity was not significantly increased. However, in cells derived from both species mitochondrial palmitate beta-oxidation was increased (rat 2.5-fold; monkey 1.5-fold). These results indicate that the species differences in the increase in peroxisomal fatty acid oxidation are not a result of an inability to metabolize fatty acids in rat liver cell mitochondria. A comparison of the activity of enzymes involved in the detoxification of hydrogen peroxide showed that catalase and glutathione-S-transferase activity is 2.9-fold higher in monkey hepatocytes than in rat liver cells, while glutathione peroxidase activity was 1.6-fold higher in rat cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mennes
W C
WC
Research Institute of Toxicology (RITOX), Utrecht University, The Netherlands.
Wortelboer
H M
HM
Hassing
G A
GA
van Sandwijk
K
K
Timmerman
A
A
Schmid
B P
BP
Jahn
U
U
Blaauboer
B J
BJ
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D002994:Clofibrate / Q000031:analogs & derivatives* / Q000494:pharmacology; D002995:Clofibric Acid / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000960:Hypolipidemic Agents; D010168:Palmitates; D002995:Clofibric Acid; C045921:beclobrinic acid; D002374:Catalase; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D002994:Clofibrate