Antioxidant action of Foy in an experimental model of hypergeneration of oxygen free radicals

Several trials have just demonstrated the therapeutic efficacy of gabexate mesylate (Foy). For this drug numerous mechanisms of action have been postulated; protease inhibition, direct or indirect lysosomal membrane stabilization, etc. The aim of this study has been to verify if Foy would express antioxidant properties against free radical overgeneration, responsible for the increase in microvascular permeability which represents one of the most important pathogenetic phenomenon of any condition of shock. A mixture of hypoxanthine-xanthine oxidase has been used to obtain a generation of oxygen free radicals in vivo.Experiments were performed on the mesocecum of male Wistar rats; fluorescent labelled bovine albumin has been injected intra-arterially to evaluate the capillary permeability and the mesocecum microcirculation has been observed by fluorescent microscopy. The control group received saline i.v., the second group received topically applied on the mesocecum a mixture of 0.96 mM hypoxanthine and 0.05 UI/ml xanthine oxidase; the third and the fourth groups were pretreated respectively with a topical application and continuous infusion of a Foy 1% solution (50 ml/kg/min). To evaluate capillary permeability and to quantify the degree of extravasation by counting the number of leaky sites, labelled bovine albumin was injected i.a. and mesocecum was observed with fluorescent microscopy for 2 hours.Gabexate mesilate (Foy) exerts its efficacy preventing the increase in capillary permeability provoked by an overgeneration of free radicals; it could express antioxidant properties.