Metalloporphyrin CoIIITMPyP Ameliorates Acute, Sublethal Cyanide Toxicity in Mice

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• 作者：Oscar S. Benz ; Quan Yuan ; Andrew A. Amoscato ; Linda L. Pearce ; Jim Peterson
• 刊名：Chemical Research in Toxicology
• 出版年：2012
• 出版时间：December 17, 2012
• 年：2012
• 卷：25
• 期：12
• 页码：2678-2686
• 全文大小：377K
• 年卷期：v.25,no.12(December 17, 2012)
• ISSN：1520-5010

文摘

The formation of Co^IIITMPyP(CN)₂ at pH 7.4 has been shown to be completely cooperative (伪_H = 2) with an association constant of 2.1 (卤0.2) 脳 10¹¹. The kinetics were investigated by stopped-flow spectrophotometry and revealed a complicated net reaction exhibiting 4 phases at pH 7.4 under conditions where cyanide was in excess. The data suggest molecular HCN (rather than CN^{鈥?/sup>) to be the attacking nucleophile around neutrality. The two slower phases do not seem to be present when cyanide is not in excess, and the other two phases have rates comparable to that observed for cobalamin, a known effective cyanide scavenger. Addition of bovine serum albumin (BSA) did not affect the cooperativity of cyanide binding to CoIIITMPyP, only lowered the equilibrium constant slightly to 1.2 (卤0.2) 脳 1011 and had an insignificant effect on the observed rate. A sublethal mouse model was used to assess the effectiveness of CoIIITMPyP as a potential cyanide antidote. The administration of CoIIITMPyP to sodium cyanide intoxicated mice resulted in the time required for the surviving mice to right themselves from a supine position being significantly decreased (9 卤 2 min) compared to that of the controls (33 卤 2 min). All observations were consistent with the demonstrated antidotal activity of CoIIITMPyP operating through a cyanide-binding (i.e., scavenging) mechanism.}