"In vitro" differences among (R) and (S) enantiomers of profens in their activities related to articular pathophysiology

Inflammation. 2005 Dec;29(4-6):119-28. doi: 10.1007/s10753-006-9003-1.

Abstract

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.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cartilage, Articular / cytology
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / physiology*
  • Cell Survival
  • Cells, Cultured
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Chondrocytes / physiology*
  • Dinoprostone / metabolism
  • Femur Head
  • Flurbiprofen / chemistry
  • Flurbiprofen / pharmacology*
  • Glycosaminoglycans / metabolism
  • Humans
  • Interleukin-1beta / pharmacology
  • Ketoprofen / chemistry
  • Ketoprofen / pharmacology*
  • Matrix Metalloproteinase 3 / metabolism
  • Nitrites / metabolism
  • Reactive Oxygen Species
  • Stereoisomerism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Glycosaminoglycans
  • Interleukin-1beta
  • Nitrites
  • Reactive Oxygen Species
  • Flurbiprofen
  • Ketoprofen
  • Matrix Metalloproteinase 3
  • Dinoprostone