S-Ibuprofen Effectively Inhibits Thromboxane B₂ Levels and Platelet Function in an Experimental Model of Lipopolysaccharide-Stimulated and Non-Stimulated Whole Blood

Abstract

Objective: The present study aimed at testing the effect of S- and R-ibuprofen on thromboxane B₂ (TXB₂), collagen-epinephrine closure time (CEPI-CT) and collagen-adenosine 5′-diphosphate closure time (CADP-CT) in lipopolysaccharide (LPS)-stimulated and non-stimulated human whole blood. Materials and Methods: Whole blood was incubated with S- or R-ibuprofen with and without prior stimulation with LPS. To verify ibuprofen’s potential effects on TXB₂, varying ratios of concentrations of S- and R-ibuprofen ranging from 0 to 100% were used. TXB₂ levels were measured by ELISA. The effects of S- and R-ibuprofen enantiomers on platelet aggregability were tested utilizing a PFA-100 apparatus. Results: In non-stimulated and LPS-stimulated whole blood, S-ibuprofen markedly decreased TXB₂ levels at concentrations ranging from 10 to 200 µg/ml. R-ibuprofen showed its inhibiting effect at concentrations >100 µg/ml. In inflammatory and non-inflammatory conditions, CEPI-CT was prolonged at concentrations of 12.5 and 75 µg/ml for S-ibuprofen and at a concentration of 150 µg/ml of combined R- and S-ibuprofen. S-ibuprofen was significantly more effective than R-ibuprofen (p < 0.05). The combined use of S- and R-ibuprofen did not additively or synergistically prolong CEPI-CTs. CADP-CTs remained unaffected by both enantiomers. Conclusions: S-ibuprofen was more effective than the R-ibuprofen enantiomer in inhibiting TXB₂ plasma levels and aggregability of thrombocytes in non-inflammatory and inflammatory conditions.

Inhibition of Thromboxane A2-Induced Arrhythmias and Intracellular Calcium Changes in Cardiac Myocytes by Blockade of the Inositol Trisphosphate Pathway

“…TXA 2 is released during myocardial ischemia and the level is proportional to the number of arrhythmias that occur (Coker et al, 1981;Hirsh et al, 1981). In addition, TXA 2 is released by inflammatory cytokines (Takayama et al, 2005;Kaehler et al, 2008). It is possible that endogenous TXA 2 that is released during tissue damage or inflammation induces direct effects on the heart in addition to the indirect actions caused by platelet aggregation and vasoconstriction.…”

Membrane Interactivity of Non-steroidal Anti-inflammatory Drugs: A Literature Review

“…The S(+)-enantiomers are responsible for beneficial and adverse effects [139]. S(+)-Ibuprofen, S(+)-ketoprofen and S(+)naproxen are more effective in inhibiting human platelet aggregation and suppressing human platelet prostaglandin production than R(-)ibuprofen [140], R(-)-ketoprofen [141] and R(-)naproxen [142], respectively.…”

ADIDAC Trial: Analgesia with Dexibuprofen versus Ibuprofen in Patients Suffering from Primary Dysmenorrhea: A Crossover Trial

“…Furthermore, possible adverse effects, which might be mediated by the R -enantiomer, could be minimized while keeping the risk of cardiovascular events as low as possible [10] . Indeed an in vitro study showed that in clinically relevant concentrations the R -enantiomer may exert a prothrombotic effect by enhancing thromboxane B 2 levels under lipopolysaccharide-stimulated conditions [15] . Several clinical trials and postmarketing surveillance studies were performed to broaden the findings on dexibuprofen.…”