The effects of dipyrone on platelet cyclooxygenase and lipoxygenase were investigated in vitro by the study of 1-'4C arachidonic acid (AA) conversion by high performance liquid chromatography (HPLC) on washed platelets at seven different drug concentrations (from 5 to 300 μg/ml). The effects of dipyrone on thromboxane (TX) B2 generation from endogenous AA were also studied in platelet-rich plasma and in washed platelets by radioimmunoassay. In the study of 1-14C AA metabolism the inhibitory concentration (IC) 50 for TXB2 was 40 μg/ml. However, at the lowest drug concentration (5 μg/ml) a slight but significant inhibition was found (25 · 3%, P <0 · 001) and a complete one at 300 μg/ml. A relationship between TXB2 inhibition and log drug concentration was found (r = 0 · 97, P <0 · 001). Lipoxygenase (LO) activity showed an increase of 45 · 9% at 20 μg/ml and of 251 5% at the highest concentration (r= 0 · 97, P <0 · 001). The inhibition of TXB2 generation from endogenous AA by washed platelets was of the same order of magnitude of the inhibition of TXB2 production from exogenous 1-4C AA. Our results indicate that dipyrone affects intraplatelet AA metabolism at very low concentrations, however its activity, on a molar ratio basis, appears to be lower than that of other non-steroidal anti-inflammatory drugs.
- arachidonic acid
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