The pharmacology of ebselen.

Ebselen has been demonstrated to be an effective anti-inflammatory agent in a variety of experimental modelsin vivo which differ from classical tests in that the aetiological roles of hydroperoxides and/or lipoxygenase products appear to be greater. Indeed, ebselen exhibits only weak anti-inflammatory activity in the traditional prostaglandin-dominated models, such as carrageenan paw oedema, adjuvant arthritis and yeast paw hyperalgesia [50]. The major targets of this anti-inflammatory activity appear to be plasma exudation and infiltration, possibly as a result of the inhibition of the hydroperoxide and/or leukotriene effects on leukocyte-endothelium interactions. Both reactive oxygen species [24] and LTB4 [51, 52] enhance granulocyte adhesiveness to endothelium and ebselen inhibits the generation of reactive oxygen species, catalyses the breakdown of hydroperoxides, inactivates LTB4 by isomerization and inhibits 5-lipoxygenase [9–11, 13–16, 27–29]. Consequently, any or all of these mechanisms of action, together with inhibition of hypoxic-reperfusion injury [53], could contribute to the anti-inflammatory activity of ebselen.