Enzyme therapy in cyanide poisoning: Effect of rhodanese and sulfur compounds
Tóm tắt
Crystalline bovine liver rhodanese (thiosulfate: cyanide sulfurtransferase, EC 2.8.1.1) was evaluated as an antidote in combination with different sulfur compounds against cyanide poisoning in mice. The prophylactic antidote effect, when the antidote was injected i.v. 1 min prior to i.p. injection of cyanide, was dependent on both the dose of the enzyme and the dose of the sulfur compound. An optimal dose of the enzyme of about 2,000 U/kg (3 mg/kg of pure enzyme) was found. This enzyme dose combined with 2 mmol/kg of sodium thiosulfate raised the LD50 for potassium cyanide 7.6 times. When thiosulfate was replaced with equimolar doses of ethanethiosulfonate and propanethiosulfonate, the corresponding values were 10.3 and 9.3 times, respectively. Maximum antidote effect was obtained when the doses of ethanethiosulfonate and propanethiosulfonate were raised to 4 mmol/kg, increasing the LD50 for cyanide 20.8 and 15.4 times, respectively. On the other hand, when given without rhodanese, ethanethiosulfonate and propanethiosulfonate were no better antidotes than thiosulfate. Rhodanese and a sulfur compound given therapeutically to mice when symptoms of cyanide poisoning had occurred, also had a very good antidote effect. The prophylactic antidote effect of rhodanese plus thiosulfate rapidly decreased with increasing time interval between injection of the antidote and cyanide. Thus, when rhodanese and thiosulfate were given 20 min prior to cyanide, the antidote effect was of the same order as that of thiosulfate alone. The antidote effect of the latter did not decrease significantly within the same time interval. Enzyme activity in plasma decreased rapidly after i.v. injection of rhodanese, and enzyme activity in urine was detected following injection. No appreciable inactivation occurred when the enzyme was incubated with whole blood in vitro, but a strong and rapid inhibition, about 85%, of the enzyme occurred in fresh mouse urine in vitro.
Tài liệu tham khảo
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