Do antidotes for acute cyanide poisoning act on mercaptopyruvate sulfurtransferase to facilitate detoxification?
A well-known combined therapy for acute cyanide poisoning is intravenous administration of sodium nitrite, sodium thiosulfate and cobalt EDTA. Sodium nitrite oxidizes oxy-hemoglobin, resulting in methemoglobin, which has a high affinity for cyanide. Sodium thiosulfate is a substrate of thiosulfate: cyanide sulfurtransferase (rhodanese, EC.2.8.1.1), and facilitates catalytic metabolism of cyanide to less toxic thiocyanate. Cobalt EDTA combines with cyanide to reduce cyanide in the blood. Here, we focus on cytosolic and mitochondrial mercaptopyruvate sulfurtransferase (MST, EC. 2.8.1.2), which detoxifies cyanide more effectively than rhodanese, because rhodanese is localized only in mitochondria. Thiosulfate also serves as a substrate of MST and cyanide can be metabolized to thiocyanate. However, the K(m) value for thiosulfate is so large that it is not expected to contribute much to the detoxification of cyanide. On the other hand, nitrite and cobalt EDTA did not affect MST. Thus, combined therapy only slightly acts on MST to detoxify cyanide. Some investigators have attempted a new therapy in which mercaptopyruvate, a substrate of MST was administered intravenously, but this was not effective for detoxification due to the rapid decomposition of mercaptopyruvate in the blood. There are two possible strategies to facilitate MST activities: development of modified mercaptopyruvate with a longer half time and development of a chemical compound which indirectly increases transcription of MST via regulation of a DNA binding protein.
Nagahara
Noriyuki
N
Department of Environmental Medicine, Nippon Medical School,Tokyo, Japan. noriyuki@nms.ac.jp
Li
Qing
Q
Sawada
Nori
N
D000208:Acute Disease; D000931:Antidotes / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects / Q000235:genetics; D003486:Cyanides / Q000506:poisoning*; D004492:Edetic Acid / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D013466:Sulfurtransferases / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D000931:Antidotes; D003486:Cyanides; D004492:Edetic Acid; D013466:Sulfurtransferases; C021550:3-mercaptopyruvate sulphurtransferase