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Inhibition of mitochondrial beta-oxidation of fatty acids by pirprofen. Role in microvesicular steatosis due to this nonsteroidal anti-inflammatory drug.
- Source :
- The Journal of Pharmacology and Experimental Therapeutics; September 1987, Vol. 242 Issue: 3 p1133-1137, 5p
- Publication Year :
- 1987
-
Abstract
- Administration of pirprofen may produce microvesicular steatosis of the liver in humans. The effects of pirprofen on the mitochondrial beta-oxidation of fatty acids have been investigated in mice. In vitro, addition of 2 mM pirprofen decreased by 50% the formation of [14C]acid-soluble beta-oxidation products, and decreased by 70% the formation of [14C]CO2 upon incubation of hepatic mitochondria with [14C]palmitic acid, ATP, carnitine and coenzyme A. In vivo, administration of pirprofen (2 mmol . kg-1 i.p.), 1 hr before that of [U-14C]palmitic acid, decreased by 70% the exhalation of [14C]CO2 during the next 6 hr. Administration of pirprofen (2 mmol . kg-1 i.p.), 1 hr before the measurement, decreased plasma beta-hydroxybutyrate by 60%, plasma acetoacetate by 30% and blood glucose by 40%. Administration of pirprofen (2 mmol . kg-1 i.p.) 6 hr before sacrifice, doubled hepatic triglycerides content and produced microvesicular steatosis of the liver. We conclude that pirprofen inhibits the mitochondrial beta-oxidation of fatty acids in mice, thus explaining the microvesicular steatosis observed in mice and in some human subjects.
Details
- Language :
- English
- ISSN :
- 00223565 and 15210103
- Volume :
- 242
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- The Journal of Pharmacology and Experimental Therapeutics
- Publication Type :
- Periodical
- Accession number :
- ejs29417088