PMID- 21762775
OWN - NLM
STAT- MEDLINE
DCOM- 20120413
LR  - 20131121
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Linking)
VI  - 25
IP  - 8
DP  - 2011 Dec
TI  - In vitro evaluation of (S)-ibuprofen toxicity on joint cells and explants of 
      cartilage and synovial membrane.
PG  - 1944-52
LID - 10.1016/j.tiv.2011.06.018 [doi]
AB  - Intra-articular drug delivery systems (DDSs) are envisaged as interesting 
      alternative to locally release nonsteroidal anti-inflammatory drugs (NSAIDs), 
      such as ibuprofen to reduce pain in patients with osteoarthritis. The present 
      study examines the toxicity of (S)-ibuprofen on chondrocytes and synoviocytes 
      isolated from sheep shoulder joint and cultured in monolayers during 72 h, and on 
      joint explants (cartilage and capsule) cultured in mono- or in co-culture for 13 
      days. (S)-ibuprofen (5 muM up to 1 mM) did not reduce the cell viability and 
      protein content when added on chondrocyte monolayers, while at 1 mM (S)-ibuprofen 
      reduced (by 8%, p=0.01) the synoviocytes viability compared to untreated cells. 
      During co-culture of joint explants, (S)-ibuprofen at 50 muM significantly reduced 
      by 35% the spontaneous release of glycosaminoglycans (GAGs) from cartilage 
      (p=0.0065) whereas in monoculture, (S)-ibuprofen was inactive on GAG metabolism. 
      (S)-ibuprofen at 1 mM significantly reduced cell lysis (lactate dehydrogenase 
      leakage) by 74% during monoculture of capsule explants (p=0.0136) and by 35% 
      during co-culture of explants (p=0.0013). Our findings demonstrate that the 
      active isomer of ibuprofen at micro- and millimolar levels was not toxic for 
      chondrocytes and synoviocytes and may reduce at 1mM the cell lysis during culture 
      of joint explants. The limited toxicity of (S)-ibuprofen at low and high 
      concentration in sheep joint shoulder makes this enantiomer a promising drug 
      candidate for the loading of intra-articular DDS.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Bedouet, Laurent
AU  - Bedouet L
AD  - Occlugel, 24 rue du Faubourg Saint Jacques, 75015 Paris, France. 
      bedouet.occlugel@orange.fr
FAU - Pascale, Florentina
AU  - Pascale F
FAU - Bonneau, Michel
AU  - Bonneau M
FAU - Wassef, Michel
AU  - Wassef M
FAU - Laurent, Alexandre
AU  - Laurent A
LA  - eng
PT  - Journal Article
DEP - 20110704
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Glycosaminoglycans)
RN  - 0 (Proteins)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - WK2XYI10QM (Ibuprofen)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*toxicity
MH  - Cartilage/*drug effects/metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chondrocytes/*drug effects/metabolism
MH  - Fibroblasts/*drug effects/metabolism
MH  - Glycosaminoglycans/metabolism
MH  - Ibuprofen/*toxicity
MH  - Joints
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Matrix Metalloproteinases/metabolism
MH  - Proteins/metabolism
MH  - Sheep
MH  - Shoulder
MH  - Synovial Membrane/cytology/*drug effects/metabolism
EDAT- 2011/07/19 06:00
MHDA- 2012/04/14 06:00
CRDT- 2011/07/19 06:00
PHST- 2010/11/23 00:00 [received]
PHST- 2011/06/24 00:00 [revised]
PHST- 2011/06/29 00:00 [accepted]
PHST- 2011/07/19 06:00 [entrez]
PHST- 2011/07/19 06:00 [pubmed]
PHST- 2012/04/14 06:00 [medline]
AID - S0887-2333(11)00186-X [pii]
AID - 10.1016/j.tiv.2011.06.018 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2011 Dec;25(8):1944-52. doi: 10.1016/j.tiv.2011.06.018. Epub 
      2011 Jul 4.