Cyanide Detoxification by the Cobalamin Precursor Cobinamide
Autor: | Prasanth Potluri, Renate B. Pilz, Gerry R. Boss, Vijay S. Sharma, Immo E. Scheffler, Shunhui Zhuang, Kate E. Broderick |
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Rok vydání: | 2006 |
Předmět: |
Cobalamin biosynthesis
medicine.medical_treatment Cyanide Smoke inhalation 0211 other engineering and technologies 020101 civil engineering CHO Cells 02 engineering and technology Oxidative phosphorylation Cobalamin General Biochemistry Genetics and Molecular Biology 0201 civil engineering chemistry.chemical_compound Cricetinae Detoxification medicine Animals Humans Vitamin B12 Antidote 021110 strategic defence & security studies Cyanides Molecular Structure Chemistry Smoke Inhalation Injury medicine.disease Vitamin B 12 Drosophila melanogaster Biochemistry Inactivation Metabolic Vitamin B Complex Cobamides |
Zdroj: | Experimental Biology and Medicine. 231:641-649 |
ISSN: | 1535-3699 1535-3702 |
DOI: | 10.1177/153537020623100519 |
Popis: | Cyanide is a highly toxic agent that inhibits mitochondrial cytochrome-c oxidase, thereby depleting cellular ATP. it contributes to smoke inhalation deaths in fires and could be used as a weapon of mass destruction. Cobalamin (vitamin B12) binds cyanide with a relatively high affinity and is used in Europe to treat smoke inhalation victims. Cobinamide, the penultimate compound in cobalamin biosynthesis, binds cyanide with about 1010 greater affinity than cobalamin, and we found It was several-fold more effective than cobalamin in (i) reversing cyanide inhibition of oxidative phosphorylation in mammalian cells; (ii) rescuing mammalian cells and Drosophila melanogaster from cyanide toxicity; and (iii) reducing cyanide inhibition of Drosophila Malpighian tubule secretion. Cobinamide could be delivered by oral ingestion, inhalation, or injection to Drosophila, and it was as effective when administered up to 5 mins post-cyanide exposure as when given preexposure. We conclude that cobinamide is an effective cyanide detoxifying agent that has potential use as a cyanide antidote, both in smoke inhalation victims and in persons exposed to cyanide used as a weapon of mass destruction. |
Databáze: | OpenAIRE |
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