Cyanide toxicity in mice pretreated with diethylamine nitric oxide complex

1 Since the literature suggested a portion of the overall toxicity of cyanide (CN) may be affected by nitric oxide, we investigated a long acting NO releasing complex (diethylamine/nitric oxide (DEA/NO)) which may exhibit vasodilatory as well as other nitric oxide effects to determine its ability to modify CN toxicity. Sodium nitrite, a vasodilator commonly used to treat cyanide toxicity thought to act by methemoglobin (MHb) formation, can be rapidly transformed to nitric oxide (NO). 2 Mice (n=10 per dose) were administered one of five doses of sodium cyanide (NaCN) intraperitoneally (4.28,5.08,6.03,7.17 and 8.52 mg kg(-1)). DEA/NO was given intravenously (20 mg kg(-1)) 2 min prior to NaCN. As a control, NG-monomethyl-L-arginine (L-NMMA), which inhibits NO synthesis, was administered intravenously (70 mg kg(-1)) to mice, 3 min prior to DEA/NO. 3 Before CN toxicity studies, we determined whether DEA/NO was producing MHb by collecting tail vein blood from mice and measuring MHb levels. For example, 4 min after DEA/NO administration (5,10, and 20 mg kg(-1)), MHb levels were 1.27+/-0.28%, 2.60+/-0.26% and 6.53+/-0.54% respectively. O-2 capacity was also decreased in a dose related manner. Carboxyhemoglobin or percent O-2 saturation, on the other hand, was not significantly inhibited. The LD(50) increased from 5.75+/-0.026 (CN alone) to 7.66+/-0.021 mg kg(-1) (CN+DEA/NO) resulting in a protective ratio of 1.73. 4 Results suggest the following: (1) L-NMMA, which inhibits the synthesis of endogenous NO, appears to exacerbate the DEA/NO (or exogenous NO) response; (2) DEA/NO appears to reduce the toxicity of CN which suggests that a portion of CN toxicity may be affected by a NO component; and (3) low DEA/NO doses map act via a direct effect while higher doses (40 mg kg(-1)) may allow for formation of a concentration of MHb which can bind CN to form cyanomethemoglobin and reduce the toxicity of CN.