The antidotal activities of aquocobalamineacetates and sodium thiosulfate were tested in guinea pigs and cats. The animals were attached to artificial respirators throughout the experiment and were poisoned with a continuous infusion of sodium cyanide solution (4.1 muMol/kg.min NaCN). The rate of action of each antidote was determined from the time taken for the HCN exhalation to drop below the level of 100 nMol/kg.min in quinea pigs, and to values below 25 nMol/kg.min in cats; the detoxifying capacity of each antidote was determined from the time taken for the HCN exhalation to rise above the said values and the time interval for normal function of heart activity to be restored. Aquobalamine was characterized by its rapid rate of reaction in both the animal species; its detoxifying capacity showed, however, according to our expectations, variations corresponding to the applied doses. The combination of the antidotes aquocobalamine (100 mg/kg) and thiosulfate (500 mg/kg) proved to possess high rate of reaction and a large detoxifying capacity in guinea pigs. Similar results were obtained in cats with antidote doses of 200 mg/kg aquocobalamine combined with 500 mg/kg thiosulfate. The slow rate of reaction and large detoxifying capacity of thiosulfate were confirmed in our experiments. It combination with aquocobalamine showed no undesirable change in its antidotal action providing a time interval of 1 min was maintained between the 2 injections.
Single doses of sodium cyanide (60 mumol/kg body weight s.c.) were administered to male Sprague-Dawley rats. The effects of this poison on the content of the trace elements zinc, copper and manganese was investigated in various organs after 30 min, 2 h, 24 h, 48 h and 1 week. The zinc content in the liver was elevated 24 h after this sublethal cyanide dose (by approximately 20%). In contrast, the copper content in the kidneys was lowered (by approximately 15%) at the same time. Almost similar changes were observed in the same organs after daily administration of the poison for 5 days. For comparison, another group of rats was allowed to respire for 30 min the air that contained only 10% oxygen. The above changes in the trace element concentrations were not observed under these conditions. After sublethal cyanide poisoning there seemed be slight but specific alterations in the trace element concentrations in the liver and kidneys of rats. On the other hand, there were no alterations in serum, heart, lung, brain, muscle, bone or testes. Up to now there is no clearcut explanation for the development and the possible biochemical importance of these results.
Lead levels in whole blood could be determined reliably up to a lower limit of 2 micrograms/100 ml blood, using a modified micromethod of the graphite tube furnace technique. Lead contents of various tissues were also determined by using the automated graphite tube furnace after wet ashing of the organs with nitric acid in autoclaves. Animal experiments with mice showed no measurable increase in blood lead level after a single, 10- or 30-days oral administration of lead in doses of 10--1000 micrograms lead acetate/kg body weight/day. However, these doses led to a rise in tissue lead content. There was a clear dependence of tissue lead content on type of organ examined, lead dose and duration of lead exposure. According to our experiments, the threshold dose which leads to a long-term increase in tissue lead content is assumed to be about 100 micrograms lead acetate/kg body weight/day, orally administered.
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