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Baskin SI, Nealley EW, Lempka JC: Cyanide toxicity in mice pretreated with diethylamine nitric oxide complex. Hum Exp Toxicol. 1996 Jan;15(1):13-18.
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. O2 capacity was also decreased in a dose related manner. Carboxyhemoglobin or percent O2 saturation, on the other hand, was not significantly inhibited. The LD50 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 may 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. |
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