Interactions of anti-inflammatory 2-arylpropionates (profens) with the metabolism of fatty acids: in vitro studies.
This review shows conclusively that profens can enter physiological pathways of lipid biochemistry. The first step in this interaction is the formation of an acyl-CoA thioester. These conjugates can lead to the incorporation of the xenobiotic acid into lipids. The resulting hybrid triglycerides have the potential to form long-lasting residues in adipose tissues and to be incorporated into membranes. Furthermore, the acyl-CoA conjugate may also alter lipid biochemistry by inhibiting lipid beta-oxidation either by interfering with the acyl-CoA synthetases or by modifying CoA levels. Thus, the acyl-CoA conjugates of profens intermediates in the inversion of inactive (R)-profens to active (S)-profens can be viewed as pivotal to bioactivation and to pathways of potential toxicity.
School of Pharmacy, University of Lausanne, Switzerland.
J M
JM
Mayer
M
M
Roy-De Vos
C
C
Audergon
B
B
Testa
J C
JC
Etter
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism*; D007052:Ibuprofen / Q000378:metabolism / Q000494:pharmacology; D050356:Lipid Metabolism; D010084:Oxidation-Reduction; D010666:Phenylpropionates / Q000378:metabolism / Q000494:pharmacology*; D014280:Triglycerides / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005227:Fatty Acids; D010666:Phenylpropionates; D014280:Triglycerides; D007052:Ibuprofen