The effects of EDRF/NO releasers or calcium ionophore A23187 on cyanide toxicity in mice.
Toxicol Appl Pharmacol
; 139(2): 349-55, 1996 Aug.
Article
em En
| MEDLINE
| ID: mdl-8806852
ABSTRACT
Cyanide (CN) is a well-recognized poison whose complete actions are unclear. It has been shown that a vasoactive role may be partially responsible for the toxic effects of CN. Sodium nitrite, a known methemoglobin former and vasodilator, has been used to treat CN toxicity. It is rapidly transformed to nitric oxide (NO) which is thought to be endothelium-derived relaxing factor (EDRF). Since the literature suggests that NO can influence the biological effects of CN, studies were undertaken to determine if compounds known to release EDRF/NO will modify CN toxicity. Mice were administered a series of compounds which act through EDRF/NO release. These substances included, platelet-activating factor (PAF), hydralazine, bradykinin, histamine, calcium ionophore A23187, carbachol, or substance P at 0.060, 98.7, 50.0, 125, 1.0, 2.26, and 1.0 mg/kg, respectively. As a control, NG-monomethyl-L-arginine (NMA) 70 mg/kg, which inhibits NO synthesis, was administered to mice iv (tail vein) in combination with each test compound. All test compounds and NMA were administered prior to NaCN NMA, 5 min; carbachol, 0.5 min; hydralazine, 0.5 min; bradykinin, 1 min; histamine, 1 min; substance P, 4 min; PAF, 5 min; and A23187, 5 min. Dose-response relationships were analyzed by probit dose-response methods and protective ratios for each compound were computed. Results suggest (i) that a portion of the action of CN is affected by a particular EDRF/NO-releasing compound, suggesting that each drug specifically affects regional EDRF/NO receptor sites, and (ii) that NO can play a role as a component in CN intoxication. It is suggested that CN does not act uniformly on all EDRF/NO receptor sites to produce toxicity and site-specific EDRF/NO agents may be useful for treating CN.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Calcimicina
/
Cianetos
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Ionóforos
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Óxido Nítrico
Limite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA