Effects of ubiquinone and mevalonic acid on hepatic peroxisomal enzymes induced by dehydroepiandrosterone.
The adrenal steroid, dehydroepiandrosterone (DHEA) has been identified as a peroxisome proliferator. We examined the effects of the cellular antioxidant ubiquinone and its precursor mevalonic acid on the induction of enzymes associated with DHEA-mediated peroxisome proliferation in male F-344 rats. Upon treatment with DHEA (300 mg/kg orally for 14 days), there was a significant increase in hepatic activities of peroxisomal beta-oxidation (3 fold), 3-ketoacyl-CoA thiolase (4 fold) and catalase (1.8 fold). Co-administration of either mevalonic acid (100 mg/kg intraperitoneally) or ubiquinone (50 mg/kg orally) with DHEA significantly attenuated the DHEA-mediated induction of these enzymes. However, neither ubiquinone nor mevalonic acid alone significantly altered peroxisomal enzyme activities in rat liver. These data suggest that exogenous administration of ubiquinone or mevalonic acid can modulate the induction of the enzymes involved in peroxisome proliferation.
Khan
S A
SA
Department of Molecular Pharmacology & Therapeutics, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Nyce
J W
JW
D000102:Acetyl-CoA C-Acyltransferase / Q000096:biosynthesis; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D002374:Catalase / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008798:Mevalonic Acid / Q000494:pharmacology*; D008830:Microbodies / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D011916:Rats, Inbred F344; D013056:Spectrophotometry, Ultraviolet; D014451:Ubiquinone / Q000494:pharmacology*
D014451:Ubiquinone; D003687:Dehydroepiandrosterone; D002374:Catalase; D000102:Acetyl-CoA C-Acyltransferase; D008798:Mevalonic Acid