CYANIDE ANTAGONISM WITH CARRIER ERYTHROCYTES AND ORGANIC THIOSULFONATES

Previous studies reported that resealed erythrocytes containing rhodan ese (CRBC) and Na2S2O3 rapidly metabolize cyanide to the less toxic th iocyanate both in vitro and in vivo. This provided a new conceptual ap proach to prevent and treat cyanide intoxication. Although the rhodane se-containing carrier cells with thiosulfate as the sulfur donor were efficacious, this approach has potential disadvantages, as thiosulfate has limited penetration of cell membrane and product inhibition of rh odanese can occur due to inorganic sulfite accumulation. In order to c ircumvent substrate limitation and product inhibition by sodium thiosu lfate, organic thiosulfonates were explored. These thiosulfonates have higher lipid solubility than thiosulfate and therefore can replenish the depleted sulfur donor, as they can readily penetrate cell membrane s. Also, product inhibition of rhodanese is less apt to occur. This ch ange in sulfur donors should greatly enhance cyanide detoxication, rep lenish the sulfur donor, and minimize product inhibition of rhodanese. Present studies demonstrate the enhanced efficacy of exogenous organi c thiosulfonates over sodium thiosulfate in the CRBC antidotal system to detoxify the lethal effects of cyanide either alone or in combinati ons with exogenously administered NaNO2. Murine carrier erythrocytes c ontaining purified bovine liver rhodanese were administered intravenou sly into male Balb/C mice. Subsequently, butanethiosulfonate (BTS) or Na2S2O3 (ip), and NaNO2 (sc) were co-administered prior to KCN (sc). P otency ratios, derived from the LD,, values, were compared in groups o f mice treated with CRBC-Na2S2O3, or CRBC-BTS either alone or in combi nation with NaNO2. The CRBC-BTS antidotal system shows strikingly enha nced protective effect over that of the CRBC-thiosulfate system either alone or in combination with sodium nitrite. (C) 1995 Society of Toxi cology.