Ebselen: a new approach to the inhibition of peroxide-dependent inflammation

Ebselen is a novel organo-selenium compound which catalytically inactivates peroxides in vitro in a manner similar to that of glutathione peroxidase (GSH-Px). In addition, ebselen also inactivates leukotriene B4 (LTB4) generated by pig leukocytes in vitro by isomerizing this eicosanoid to its biologically inactive 6-trans isomer. In vivo, ebselen is a weak oral inhibitor of carrageenan paw oedema and adjuvant arthritis in the rat, differentiating it from classical NSAIDs such as indomethacin and diclofenac. In contrast, oral ebselen, like (intra-articular) catalase, is an effective inhibitor of monoarthritis induced in mice with amidated glucose oxidase (aGO) and dose-dependently inhibits cobra-venom-factor-induced paw oedema in rats. Indomethacin and piroxicam are weakly active or ineffective in these models. The data indicate that ebselen is likely to be useful in the therapy of inflammatory conditions in which reactive oxygen species, such as peroxides, play an aetiological role.