“In Vitro” Differences among (R) and (S) Enantiomers of Profens in their Activities Related to Articular Pathophysiology

Panico, Annamaria; Cardile, Venera; Gentile, Barbara Cristina; Garufi, F.; Avondo, Sergio; Ronsisvalle, Simone

doi:10.1007/s10753-006-9003-1

Cited by 9 publications

(10 citation statements)

References 22 publications

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“…This effect is in accordance with the expected function of active isomer of profens on COX enzymes 2,21,24 . No effect of S-(þ)-ibuprofen at 50 mM on reduction of NO synthesis and proteoglycans degradation was found in contradiction with results obtained for active isomer of ketoprofen and S-(þ)-flurbiprofen which reduced at 10 mM the synthesis of NO from human chondrocytes treated with IL-1 24 .…”

Section: Discussionsupporting

confidence: 90%

“…Clinically, use of single active isomer of the profens class of NSAIDs instead of the racemate mixture may represent a reduction of dose during treatment leading to a less exposition to xenobiotics and a reduction of renal load 23 . In vitro, biological activities of several NSAIDs isomers on joint cells were analyzed: S-(þ)-ketoprofen and S-(þ)-flurbiprofen on human chondrocytes treated with interleukin-1 24 and carprofen isomers on equine chondrocytes and synoviocytes after lipopolysaccharides (LPS) treatment 25,26 . No such study was undertaken for S-(þ)-ibuprofen.…”

Section: Introductionmentioning

confidence: 99%

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In vitroevaluation of S-(+)-ibuprofen as drug candidate for intra-articular drug delivery system

Bédouet¹,

Pascale²,

Bonneau³

et al. 2013

Drug Development and Industrial Pharmacy

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Intra-articular drug delivery systems (DDSs) are envisaged as interesting alternative to locally release non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen to reduce pain in patients with osteoarthritis. The present study examines the efficacy of S-(+)-ibuprofen on cartilage degradation as drug candidate for DDS loading. Humeral cartilage and joint capsule explants were collected from healthy sheep shoulder joints and they were cultured in mono- or in co-culture for 13 days with LPS in combination with S-(+)-ibuprofen at 50 µM and 1 mM. S-(+)-ibuprofen (50 µM) blocked prostaglandins production in LPS-activated explants but did not reduce cartilage degradation. By contrast, 1 mM S-(+)-ibuprofen treatment of cartilage explants reduced nitric oxide synthesis by 51% (p = 0.0072), proteoglycans degradation by 35% (p = 0.0114) and expression of serum amyloid protein - the main protein induced upon LPS challenge - by 44% (p < 0.0001). On contrary, in presence of synovial membrane, the protective effects of S-(+)-ibuprofen on cartilage damages were significantly diminished. At 1mM, S-(+)-ibuprofen reduced the cell lysis during culture of cartilage and joint capsule either in mono- or in co-culture. This study performed on sheep explants shows that 1 mM S-(+)-ibuprofen inhibited cartilage degradation via a mechanism independent of cyclooxygenase inhibition. Reduction of prostaglandins synthesis at 50 µM in all treatment groups and reduction of cartilage degradation observed at 1 mM suggest that S-(+)-ibuprofen could be considered as a promising drug candidate for the loading of intra-articular DDS.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

In vitroevaluation of S-(+)-ibuprofen as drug candidate for intra-articular drug delivery system

Bédouet¹,

Pascale²,

Bonneau³

et al. 2013

Drug Development and Industrial Pharmacy

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show abstract

“…Likewise, ASA, but not indomethacin or acetaminophen inhibits cytokine-induced nitrite production in cardiac fibroblasts [95]. Furthermore, there was no significant difference between the S- and R- pure enantiomers of flurbiprofen and ketoprofen as regards the reduction of NO release from IL-1β stimulated human chondrocytes [96], and exogenous PGE 2 did not reverse the inhibitory effects of celecoxib on NO production by activated human articular chondrocytes [97]. …”

Section: Non-opioids and Nitric Oxidementioning

confidence: 99%

Mechanisms of Non-Opioid Analgesics Beyond Cyclooxygenase Enzyme Inhibition

Hamza¹,

Dionne²

2009

CMP

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Non-opioid analgesics including both selective and non-selective cyclooxygenase (COX) inhibitors and acetaminophen are the most widely used treatments for pain. Inhibition of COX is thought to be largely responsible for both the therapeutic and adverse effects of this class of drugs. Accumulating evidence over the past two decades has demonstrated effects of non-opioids beyond the inhibition of COX and prostaglandin synthesis that might also explain their therapeutic and adverse effects. These include their interaction with endocannabinoids, nitric oxide, monoaminergic, and cholinergic systems. Moreover, the recent development of microarray technology that allows the study of human gene expression suggests multiple pathways that may be related to the analgesic and anti-inflammatory effects of non-opioids. The present review will discuss the multiple actions of non-opioids and their interactions with these systems during inflammation and pain, suggesting that COX inhibition is an incomplete explanation for the actions of non-opioids and proposes the involvement of multiple selective targets for their analgesic, as well as, their adverse effects.

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“…The use of the pure enantiomers of flurbiprofen and ketoprofen can help answer this question, since the S-enantiomer inhibits PGE 2 synthesis, while the R-enantiomer is devoid of this property. Panico et al [96] showed in human chondrocytes that S-flurbiprofen and Sketoprofen inhibits IL-1β induced MMP-3 production to a greater extent than R-flurbiprofen and R-ketoprofen. However, R-flurbiprofen and R-ketoprofen significantly inhibited IL-1β induced MMP-3 production, suggesting that inhibition of PGE 2 production, though participating in this process, is not the sole player.…”

Section: Possible Factors Contributing To Non-opioids Effects On Mmpsmentioning

confidence: 99%

Mechanisms of Non-Opioid Analgesics Beyond Cyclooxygenase Enzyme Inhibition

Hamza¹,

Dionne²

2009

CMP

View full text Add to dashboard Cite

Non-opioid analgesics including both selective and non-selective cyclooxygenase (COX) inhibitors and acetaminophen are the most widely used treatments for pain. Inhibition of COX is thought to be largely responsible for both the therapeutic and adverse effects of this class of drugs. Accumulating evidence over the past two decades has demonstrated effects of non-opioids beyond the inhibition of COX and prostaglandin synthesis that might also explain their therapeutic and adverse effects. These include their interaction with endocannabinoids, nitric oxide, monoaminergic, and cholinergic systems. Moreover, the recent development of microarray technology that allows the study of human gene expression suggests multiple pathways that may be related to the analgesic and antiinflammatory effects of non-opioids. The present review will discuss the multiple actions of nonopioids and their interactions with these systems during inflammation and pain, suggesting that COX inhibition is an incomplete explanation for the actions of non-opioids and proposes the involvement of multiple selective targets for their analgesic, as well as, their adverse effects.

show abstract

“In Vitro” Differences among (R) and (S) Enantiomers of Profens in their Activities Related to Articular Pathophysiology

Cited by 9 publications

References 22 publications

In vitroevaluation of S-(+)-ibuprofen as drug candidate for intra-articular drug delivery system

In vitroevaluation of S-(+)-ibuprofen as drug candidate for intra-articular drug delivery system

Mechanisms of Non-Opioid Analgesics Beyond Cyclooxygenase Enzyme Inhibition

Mechanisms of Non-Opioid Analgesics Beyond Cyclooxygenase Enzyme Inhibition

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