The data obtained from our recent experiments, which were funded by the parent grant, support the view that the mono-demethylated metabolite of methylene blue, Azure B (AzB), is a very effective cyanide (CN) antidote. AzB is very well tolerated, while displaying a higher efficacy than MB at low doses. CN still represents a major public health problem in children, a question that has been greatly overlooked. For instance, there have been no studies evaluating the safety or even the efficacy in the pediatric population of nitrite compounds or hydroxocobalamin, the two main CN antidotes currently used in adult. Yet, children can be, like adults, intoxicated during smoke inhalation. In developing countries, exposure of children to CN often result from the ingestion of CN containing produces ? such as apricot kernels or cassava. The developmental consequences of an acute CN intoxication in a young child must take into account the vulnerability of the heart and the brain to the cellular ?anoxia? produced by CN. Yet, there is no structured on-going research on the treatment of children exposed to the consequences of an acute CN intoxication. The one-year proposal developed in this administrative supplement has the objective of establishing that AzB is effective in juvenile rats following oral ingestion of a lethal dose of CN, preventing death and improving the general outcome. A model of lethal CN oral intoxication will be used in 20-day old rats of either sex; AzB will be administered at different dosages, after ingestion of CN, when the animals are in a coma.
This proposal is aimed at obtaining preliminary/proof of concept data on the efficacy of Azure B against cyanide (CN) acute toxicity in juvenile rats, following oral ingestion of a lethal level of CN. Our ultimate objective is to be able to offer CN antidotes that would be effective and safe in children.
