"In vitro" differences among (R) and (S) enantiomers of profens in their activities related to articular pathophysiology.
An important group of non steroidal antinflammatory drugs (NSAIDs), which have been used for the symptomatic treatment of various forms of arthritis, are the 2-arylpropionic acid derivatives, 'profens'. By virtue of a chiral carbon atom on the propionic acid side chain, they exist as enantiomeric pairs. Whereas the S (+) enantiomer could be represented as an effective, but unselective COX inhibitor, the R (-) enantiomer could be much less active in this respect. However, recent findings suggest that certain pharmacological effects of profens cannot be attributed exclusively to the S (+) enantiomer. To obtain further insights into the pharmacological effects of profens, this study investigated the influence of pure enantiomers (S), (R), and racemic flurbiprofen and ketoprofen on the production of NO, MMP-3, PGE(2), ROS and GAGs, key molecules involved in cartilage destruction. Our results show that (S) flurbiprofen and ketoprofen decrease, at 1- and 10-microM concentrations, the interleukin-1beta induced cartilage destruction.
Panico
A M
AM
Department of Pharmaceutical Sciences, University of Catania, V.1e A. Doria 6, 95125 Catania, Italy. panico@unict.it
Cardile
V
V
Gentile
B
B
Garufi
F
F
Avondo
S
S
Ronsisvalle
S
S
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015232:Dinoprostone / Q000378:metabolism; D005270:Femur Head; D005480:Flurbiprofen / Q000737:chemistry / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D007660:Ketoprofen / Q000737:chemistry / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D017382:Reactive Oxygen Species; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006025:Glycosaminoglycans; D053583:Interleukin-1beta; D009573:Nitrites; D017382:Reactive Oxygen Species; D005480:Flurbiprofen; D007660:Ketoprofen; D019278:Matrix Metalloproteinase 3; D015232:Dinoprostone