RT Journal Article
SR Electronic
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
FD American Society for Pharmacology and Experimental Therapeutics
SP 529
OP 535
VO 255
IS 2
A1 E Freneaux
A1 B Fromenty
A1 A Berson
A1 G Labbe
A1 C Degott
A1 P Letteron
A1 D Larrey
A1 D Pessayre
YR 1990
UL http://jpet.aspetjournals.org/content/255/2/529.abstract
AB 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.