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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Local anti-inflammatory activities of tixocortol 21-pivalate, inhibition of prostaglandins and leukotrienes synthesis, in carrageenin-induced pleurisy. Reversion of effects by RU 486.

Since a direct effect of tixocortol pivalate (TP) has been described on cyclooxygenase pathway, local anti-inflammatory activities of some 21 thiol derivatives of steroids were investigated on the carrageenin-induced pleurisy model in comparison with dexamethasone (Dex) or other anti-inflammatory drugs. LTC4/D4 contents in pleural fluid were assayed by RIA as well as PGE2 levels to characterize the effects on arachidonate pathways. After oral administration, TP was inactive up to 1 g/kg on exudate volume and leukocyte migration as expected for this strict local anti-inflammatory steroid contrary to Dex (ID50 = 0.05-0.41 mg/kg). When administered locally, TP and tixocortol (T) exerted a dose dependent inhibitory activity on exudate volume (ID30 = 12.4 micrograms or 13.1 micrograms/pleural cavity) and leukocyte count (ID30 = 83 or 230 micrograms); in the same conditions. Dex was more active (ID30 = 0.7 and 2.6 micrograms). All these steroids decreased PGE2 and LTC4/D4 contents in exudate fluids, respectively TP (50 micrograms/pleural cavity) by 28 and 63%; T (100 micrograms) by 33 and 31%; Dex (5 micrograms) by 43 and 40%. Local co-administration of RU 486 (50 micrograms) with either TP, T or Dex reversed the anti-inflammatory effects of all steroids, indicating in these conditions a local activity through glucosteroid receptor occupancy.[1]

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