TY - JOUR T1 - Stereoselective and nonstereoselective effects of ibuprofen enantiomers on mitochondrial beta-oxidation of fatty acids. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 529 LP - 535 VL - 255 IS - 2 AU - E Freneaux AU - B Fromenty AU - A Berson AU - G Labbe AU - C Degott AU - P Letteron AU - D Larrey AU - D Pessayre Y1 - 1990/11/01 UR - http://jpet.aspetjournals.org/content/255/2/529.abstract N2 - The effects of the R-(-) and S-(+)ibuprofen enantiomers were first studied in vitro with mouse liver mitochondria incubated in the presence of various concentrations of exogenous coenzyme A. In the presence of a low concentration of coenzyme A (2.5 microM), the R-(-)enantiomer (which forms an acylcoenzyme A) inhibited stereoselectively the beta oxidation of [1-14C]palmitic acid but not that of [1-14C]palmitoyl-L-carnitine (which can directly enter the mitochondria). In the presence, however, of a concentration of coenzyme A (50 microM) reproducing that present in liver cell cytosol, both enantiomers (2 mM) slightly inhibited the beta oxidation of [1-14C]palmitic acid and markedly inhibited the beta oxidation of [1-14C]octanoic acid and [1-14C]butyric acid. In vivo, both enantiomers (1 mmol.kg-1) similarly inhibited the formation of [14C]CO2 from [1-14C]fatty acids. Both enantiomers similarly decreased plasma ketone bodies. Both similarly increased hepatic triglycerides, and both produced mild microvesicular steatosis of the liver. We conclude that both ibuprofen enantiomers inhibit beta oxidation of fatty acids in vitro and in vivo. In addition, the R-(-)enantiomer may stereoselectively sequester coenzyme A; at low concentrations of coenzyme A in vitro, this may stereoselectively inhibit the mitochondrial uptake and beta oxidation of long chain fatty acids. ER -