Antidotes of cyanide intoxication

Cyanide poisoning can occur from industrial disasters, smoke inhalation from fire, food, and multiple other sources. Cyanide inhibits mitochondrial oxidative phosphorylation by blocking mitochondrial cytochrome oxidase, which in turn results in anaerobic metabolism and depletion of adenosine triphosphate in cells. Rapid administration of antidote is crucial for life saving in severe cyanide poisoning. Multiple antidotes are available for cyanide poisoning. The action mechanism of cyanide antidotes include formation of methemoglobin, production of less or no toxic complex, and sulfane sulfur supplementation. At present, the available antidotes are amyl nitrite, sodium nitrite, sodium thiosulfate, hydroxocobalamin, 4-dimethylaminophenol, and dicobalt edetate. Amyl nitrite, sodium nitrite, and 4-dimethylaminophenol induce the formation of methemoglobin. Sodium thiosulfate supplies the sulfane sulfur molecule to rhodanese, allowing formation of thiocyanate and regeneration of native enzymes. Hydroxocobalamin binds cyanide rapidly and irreversibly to form cyanocobalamin. Dicobalt edetate acts as a chelator of cyanide, forming a stable complex. Based on the best evidence available, a treatment regimen of 100% oxygen and hydroxocobalamin, with or without sodium thiosulfate, is recommended for cyanide poisoning. Amyl nitrite and sodium nitrite, which induce methemoglobin, should be avoided in victims of smoke inhalation because of serious adverse effects.

Effects of Intravenous Administration of Taurocholate on Liver and Serum Thiosulfate Sulfurtransferase Activities in Cholestatic Rat

PURPOSE: To Study the possible mechanisms of change of thiosulfate sulfurtransferase (TST) activity in cholestatic rat liver and serum. METHODS: Rats were divided into seven groups: those receiving a sham operation (Sham group), with a bile duct obstruction (BDO) alone (BDO group), with a BDO plus taurocholic acid (TCA) injection (BDO plus TCA group), with a BDO plus tauroursodeoxycholic acid (TUDCA) injection (BDO plus TUDCA group), a choledocho-caval shunt (CCS) operation (CCS groups), a CCS operation plus TCA injection (CCS plus TCA group) and a CCS operation plus TUDCA injection (CCS plus TUDCA group). The TST activities in the serum and in the hepatic subcellular fractions isolated from above experimental rats were determined. The Km and Vmax values of this hepatic enzyme were measured. RESULTS: The liver cytosolic, mitochondrial and microsomal TSTs activities, as well as the TST Vmax values were found to be significantly decreased in the BDO plus TCA and BDO groups compared to the control group. The activity and Vmax value of the liver cytosolic TST were also found to be significantly decreased in the CCS plus TCA group. Conversely, there was no variation in the Km values of the hepatic enzymes in any of the above experimental groups. The serum TST activities in the CCS plus TCA and BDO plus TCA groups, were significantly increased compared with the control, CCS and BDO groups. However, the serum and hepatic enzyme activities were unchanged in both the CCS plus TUDCA and BDO plus TUDCA groups. CONCLUSION: The above results indicate that TCA represses the biosynthesis of TST in the liver. Also, the elevated TST activity in the serum is most likely due to an increase in the permeability of hepatocytes membrane upon TCA mediated liver cell necrosis.

Effects of Intravenous Administration of Taurocholate on Liver and Serum Thiosulfate Sulfurtransferase Activities in Cholestatic Rat

PURPOSE: To Study the possible mechanisms of change of thiosulfate sulfurtransferase (TST) activity in cholestatic rat liver and serum. METHODS: Rats were divided into seven groups: those receiving a sham operation (Sham group), with a bile duct obstruction (BDO) alone (BDO group), with a BDO plus taurocholic acid (TCA) injection (BDO plus TCA group), with a BDO plus tauroursodeoxycholic acid (TUDCA) injection (BDO plus TUDCA group), a choledocho-caval shunt (CCS) operation (CCS groups), a CCS operation plus TCA injection (CCS plus TCA group) and a CCS operation plus TUDCA injection (CCS plus TUDCA group). The TST activities in the serum and in the hepatic subcellular fractions isolated from above experimental rats were determined. The Km and Vmax values of this hepatic enzyme were measured. RESULTS: The liver cytosolic, mitochondrial and microsomal TSTs activities, as well as the TST Vmax values were found to be significantly decreased in the BDO plus TCA and BDO groups compared to the control group. The activity and Vmax value of the liver cytosolic TST were also found to be significantly decreased in the CCS plus TCA group. Conversely, there was no variation in the Km values of the hepatic enzymes in any of the above experimental groups. The serum TST activities in the CCS plus TCA and BDO plus TCA groups, were significantly increased compared with the control, CCS and BDO groups. However, the serum and hepatic enzyme activities were unchanged in both the CCS plus TUDCA and BDO plus TUDCA groups. CONCLUSION: The above results indicate that TCA represses the biosynthesis of TST in the liver. Also, the elevated TST activity in the serum is most likely due to an increase in the permeability of hepatocytes membrane upon TCA mediated liver cell necrosis.

Thiosulfate sulfurtransferase and UDP-glucuronosyltransferase activities in cholestatic rat liver induced by common bile duct ligation

We have investigated the effect of cholestasis on the hepatic thiosulfate sulfurtransferase (rhodanese) and UDP-glucuronosyltransferase (UDP-GT) activities in rats. Rhodanese activities in the liver cytosol, mitochondria and microsomal fractions as well as in the rat serum, and UDP-GT activity in the microsome have been investigated for a period of 42 days after common bile duct (CBD) ligation. The cytosolic rhodanese activity showed a significant decrease between the first through the 42nd day, and the mitochondrial activity showed a significant decrease between the 7th through the 42nd day after CBD ligation compared to the activities from the sham operated control, respectively. In the case of microsomal preparation, both rhodanese and UDP-GT also showed significant decrease in their activities after the ligation for the former enzyme between the 14th and the 42nd days, and for the latter enzyme between the third and 42nd days, respectively. On the other hand, the serum rhodanese activity increased markedly soon after the ligation, exhibiting the peak activity after 1 day of CBD ligation with about 4.6-fold increment. The activity subsequently decreased gradually reaching to the control level at the 42nd day post-ligation. Enzyme kinetic parameters of hepatic rhodanese and UDP-GT were analyzed using sodium thiosulfate and p-nitrophenol as substrates, respectively, with the preparations from the 28th day post-ligation. The results indicated that although the K-m values of these enzymes were about the same as the sham-operated control, the V-max values of the both enzymes decreased significantly. These results, therefore, suggest that the biosynthesis of rhodanese and UDP-GT have been reduced in response to cholestasis, and that the elevation of rhodanese activity in the serum is most likely due to leakage from the liver subsequent to CBD ligation.

Serum rhodanese in goitre and calcific pancreatitis of tropics.

Rhodanese is one of the enzymes concerned in the detoxification of cyanide. Cassava intake and consequent cyanide toxicity are incriminated in the pathogenesis of goitre and calcific pancreatitis of tropics. So we studied the activity of rhodanese in these patients. 14 controls, 13 patients with pancreatitis and 12 with goitre were studied. The median (and range) of rhodanese in these groups were 82 (50-144), 110 (64-180) and 71 (22-160) units respectively. The serum rhodanese was significantly higher (P less than 0.05) in patients with pancreatitis when compared to the other groups. There was no significant difference between the serum rhodanese in patients with goitre and the controls. The presence of adequate amounts of rhodanese indicates that goitre and chronic pancreatitis are not produced by impaired cyanide detoxification.

Pattern of enzyme changes in rabbits administered linamarin or potassium cyanide.

Diseases like tropical ataxic neuropathy and endemic goitre have been reported to have definite correlation with a chronic ingestion of cassava (Manihot esculenta Crantz). The toxicity of cassava has been attributed to its two cyanogenic glycosides, linamarin and lotaustralin. In this study, an attempt has been made to understand the pattern of changes in certain clinically significant enzymes brought about by the chronic administration of sublethal doses of linamarin to rabbits. The profound elevation in rhodanese activity observed in the linamarin and cyanide treated rabbits indicated the attempt of the tissues to detoxify cyanide. That intact linamarin could be hydrolysed in vivo was a significant finding from the study. The mode of toxicity of linamarin was similar to that of cyanide by producing a gradual shift from aerobic to anaerobic metabolism.

Partial purification and properties of rhodanese from human placenta

The optimum pH of the enzyme rhodanese [thiosulfate: cyanide sulfurtransferase, EC 2.8.1.1.] was found to be 10.5 in glycine-NaOH and 11.5 in borate-NaOH buffers. The K[m] value was found 1.1X10[-1] for cyanide and 4.0 x 10[-3] M for thiosulfate