Abstract
Background
Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside administration. This cobalt-containing compound has been shown to be devoid of significant immediate side effects during acute administration. However, its potential delayed toxicity related to cobalt accumulation in tissue remains unknown. Therefore, we evaluated the toxicity of hydroxocobalamin as compared with that of cobalt salts on rat cardiac and diaphragmatic muscles.
Methods
For a 21-day period, rats were treated intraperitoneally with either hydroxocobalamin (70 mgkg−1 per day,n=14) cobalt chloride hexahydrate (12 mg kg−1 per day,n=14) or saline (n=10). Hydroxocobalamin and cobalt chloride groups received equimolar doses of cobalt. We studied: (1) the mechanical properties of isolated left ventricular papillary muscles and diaphragmatic strips, (2) the cardiac and diaphragmatic cobalt tissue concentrations, and (3) the myocardial histological aspect.
Results
During the study period, no significant increase in body weight was noted in the cobalttreated group (−4±1%), which was in contrast to the hydroxocobalamin-treated group (+21±2%) and the saline-treated group (22±2%). Compared with controls, the mechanical properties of cardiac and diaphragmatic muscles were unchanged after either hydroxocobalamin or cobalt salt treatments, and myocardial histological characteristics were similar in all groups. Conversely, large amounts of cobalt deposit were observed in the cobalt-treated group in both the diaphragm (41.90±16.30 vs 0.70±0.40 μmol μg−1 in the control group,P<0.001). After hydroxocobalamin administration, cobalt concentrations were significantly lower in the diaphragm (25.10±16.50 μmol μg−1,P<0.001 vs cobalt-treated group) and the myocardium (4.50±1.20 μmol μg,P<0.001 vs cobalt-treated group).
Conclusion
These results indicate that repeated administration of hydroxocobalamin was devoid of significant diaphragmatic and cardiac muscle toxicity and therefore remains a safe antidote for acute cyanide poisoning.
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N. Péry and C. Coirault were the recipients of a fellowship grant from the Fondation pour la Recherche Médicale
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Péry-Man, N., Houeto, P., Coirault, C. et al. Hydroxocobalamin vs cobalt toxicity on rat cardiac and diaphragmatic muscles. Intensive Care Med 22, 108–115 (1996). https://doi.org/10.1007/BF01720716
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DOI: https://doi.org/10.1007/BF01720716