RESUMO
Resumen Las intoxicaciones derivan de la presencia en el organismo de un tóxico o veneno, la muerte por intoxicación es una muerte violenta y por tanto requiere de la realización de una autopsia medico legal, la misma puede darse en el contexto de una exposición accidental ya sea en el hogar o laboral o sucitada por un intento de autoeliminación. La intoxicación por cianuro puede ser intencional (suicidio u homicidio) o accidental, los hallazgos en la autopsia medico legal son inespecíficos por lo que son importantes los datos aportados en el informe sobre muerte en investigación, el informe del escenario de muerte en caso de que un médico forense se hiciera presente al mismo y el resultado de los análisis toxicológicos, los cuales actualmente no se realizan en la sección de toxicología del poder judicial. Se realizó una revisión bibliográfica en diferentes bases de datos, de los artículos publicados referentes al tema de los últimos cinco años, con el objetivo de revisar las caracteristicas del químico, el metabolismo y la intoxicación como tal, tanto por sus secuelas como por sus implicaciones letales. Se concluye que para mejorar la pericia médico legal ante casos de intoxicacion por cianuro es fundamental conocer el mecanismo de acción y los posibles hallazgos presentes tanto al examen externo como interno, así como implementar que dicho escrutinio se incluya dentro del listado de sustancias a analizar.
Abstract Poisoning derives from the presence of a toxic substance or poison in the body, death by poisoning is a violent death and requires a legal medical autopsy, it may occur in the context of an accidental exposure at home or work, or caused by an attempt of self-elimination. Cyanide poisoning can be intentional (suicide / homicide) or accidental, the findings in the autopsy are unspecific, so data provided in the report of death in investigation, the report of the death scene (in case a forensic doctor was present) and the result of the toxicological analyzes, which are not currently performed in the toxicology section of the judiciary, are important. A bibliographic review was carried out in different databases of articles published in the last five years on the subject, with the objective of reviewing the chemical characteristics, the metabolism and the intoxication, as well, including their sequels and lethal implications. It is concluded that to improve the medical legal expertise in cases of cyanide poisoning, it is essential to know the mechanism of action and the possible findings in the external and internal examination; and to implement such scrutiny in the list of substances to be analyzed.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Suicídio , Cianetos/intoxicação , Costa RicaRESUMO
STUDY OBJECTIVE: The 2 antidotes for acute cyanide poisoning in the United States must be administered by intravenous injection. In the out-of-hospital setting, intravenous injection is not practical, particularly for mass casualties, and intramuscular injection would be preferred. The purpose of this study is to determine whether sodium nitrite and sodium thiosulfate are effective cyanide antidotes when administered by intramuscular injection. METHODS: We used a randomized, nonblinded, parallel-group study design in 3 mammalian models: cyanide gas inhalation in mice, with treatment postexposure; intravenous sodium cyanide infusion in rabbits, with severe hypotension as the trigger for treatment; and intravenous potassium cyanide infusion in pigs, with apnea as the trigger for treatment. The drugs were administered by intramuscular injection, and all 3 models were lethal in the absence of therapy. RESULTS: We found that sodium nitrite and sodium thiosulfate individually rescued 100% of the mice, and that the combination of the 2 drugs rescued 73% of the rabbits and 80% of the pigs. In all 3 species, survival in treated animals was significantly better than in control animals (log rank test, P<.05). In the pigs, the drugs attenuated an increase in the plasma lactate concentration within 5 minutes postantidote injection (difference: plasma lactate, saline solution-treated versus nitrite- or thiosulfate-treated 1.76 [95% confidence interval 1.25 to 2.27]). CONCLUSION: We conclude that sodium nitrite and sodium thiosulfate administered by intramuscular injection are effective against severe cyanide poisoning in 3 clinically relevant animal models of out-of-hospital emergency care.
Assuntos
Antídotos/administração & dosagem , Antídotos/uso terapêutico , Cianetos/intoxicação , Nitrito de Sódio/administração & dosagem , Nitrito de Sódio/uso terapêutico , Tiossulfatos/administração & dosagem , Tiossulfatos/uso terapêutico , Animais , Antídotos/farmacologia , Modelos Animais de Doenças , Injeções Intramusculares , Masculino , Camundongos , Coelhos , Distribuição Aleatória , Nitrito de Sódio/farmacologia , Sus scrofa , Tiossulfatos/farmacologiaRESUMO
El cianuro es uno de los tóxicos más peligrosos por su rápida y potente acción, muchas veces letal. Los diferentes tratamientos de la intoxicación tienen su base o explicación en el conocimiento de la toxicocinética y la toxicodinamia. La revisión de la toxicocinética del cianuro muestra que, si bien la vía de la tiosulfato-cianuro sulfotransferasa (rodanasa) es la principal vía metabólica, el complejo con albúmina sérica sería el primer proceso de detoxificación del cianuro en el metabolismo normal. El efecto protector de formadores de cianhidrinas en casos de intoxicación sigue siendo evaluado a nivel experimental. Los estudios actuales sobre la toxicodinamia del cianuro se enfocan en la afinidad de la unión del cianuro al centro binuclear hemo a3-CuB de la citocromo oxidasa en sus diferentes estados redox y enel mecanismo de inhibición de enzimas antioxidantes. Un mayor y mejor entendimiento de la detoxificación del cianuro así como de los mecanismos de acción tóxica podrían llevar al desarrollo de potenciales antídotos.
Cyanide is one of the most dangerous poisons because of its rapid and potent toxicity, most times with lethal outcomes. Different poisoning treatments are based on knowledge of cyanides toxicokinetic and toxicodynamic. The review of cyanides toxicokinetics shows that, although thiosulfate-cyanide sulfotransferase (rhodanese) is the major metabolic pathway, binding serum albumin would be the first process of detoxification of cyanide in normal metabolism. The protective effect of cyanohydrin formers in cases of poisoning remains experimentally evaluated. Cyanides binding affinity to the binuclear center heme a3-CuB of cytochrome oxidase within their different redox states and cyanides mechanism of inhibition of antioxidant enzymes are currently still being investigated. More and better understanding of cyanides detoxification pathways and/or mechanisms of toxic action could lead to the development of new potential antidotes.
Assuntos
Cianeto de Hidrogênio/farmacocinética , Cianeto de Hidrogênio/toxicidade , Antídotos/farmacologia , Cianeto de Hidrogênio/intoxicação , Cianetos/intoxicaçãoRESUMO
El cianuro es uno de los tóxicos más peligrosos por su rápida y potente acción, muchas veces letal. Los diferentes tratamientos de la intoxicación tienen su base o explicación en el conocimiento de la toxicocinética y la toxicodinamia. La revisión de la toxicocinética del cianuro muestra que, si bien la vía de la tiosulfato-cianuro sulfotransferasa (rodanasa) es la principal vía metabólica, el complejo con albúmina sérica sería el primer proceso de detoxificación del cianuro en el metabolismo normal. El efecto protector de formadores de cianhidrinas en casos de intoxicación sigue siendo evaluado a nivel experimental. Los estudios actuales sobre la toxicodinamia del cianuro se enfocan en la afinidad de la unión del cianuro al centro binuclear hemo a3-CuB de la citocromo oxidasa en sus diferentes estados redox y enel mecanismo de inhibición de enzimas antioxidantes. Un mayor y mejor entendimiento de la detoxificación del cianuro así como de los mecanismos de acción tóxica podrían llevar al desarrollo de potenciales antídotos.(AU)
Cyanide is one of the most dangerous poisons because of its rapid and potent toxicity, most times with lethal outcomes. Different poisoning treatments are based on knowledge of cyanides toxicokinetic and toxicodynamic. The review of cyanides toxicokinetics shows that, although thiosulfate-cyanide sulfotransferase (rhodanese) is the major metabolic pathway, binding serum albumin would be the first process of detoxification of cyanide in normal metabolism. The protective effect of cyanohydrin formers in cases of poisoning remains experimentally evaluated. Cyanides binding affinity to the binuclear center heme a3-CuB of cytochrome oxidase within their different redox states and cyanides mechanism of inhibition of antioxidant enzymes are currently still being investigated. More and better understanding of cyanides detoxification pathways and/or mechanisms of toxic action could lead to the development of new potential antidotes.(AU)
Assuntos
Cianeto de Hidrogênio/farmacocinética , Cianeto de Hidrogênio/toxicidade , Antídotos/farmacologia , Cianeto de Hidrogênio/intoxicação , Cianetos/intoxicaçãoRESUMO
1. Results of studies on the kinetics of hepatic rhodanese and the effects of S-adenosyl-L-methionine (SAM) on these kinetic parameters in cyanide-treated and non-treated mice are reported here. 2. The enzyme exhibited typical Michaelis-Menten behaviour with cyanide inhibition at concentrations higher than 50 mM. Km values of 4.74 and 0.85 mM were obtained for thiosulphate and cyanide, respectively, in control mice. 3. These results stress the biological importance of the rhodanese reaction for cyanide detoxification. 4. Km values were not significantly modified when the animals were intoxicated with a lethal (20 mg/kg) or a non-lethal (4 mg/kg) dose of cyanide. 5. SAM treatment either in control or in cyanide-poisoned animals doubled the Km's for cyanide.
Assuntos
Cianetos/intoxicação , Fígado/enzimologia , Sulfurtransferases/metabolismo , Tiossulfato Sulfurtransferase/metabolismo , Animais , Cinética , Fígado/efeitos dos fármacos , Camundongos , S-Adenosilmetionina/farmacologia , Tiossulfatos/farmacologiaRESUMO
The effects of oral chronic cyanide administration to mice were studied. Cyanide intoxication was confirmed by the increased levels of this poison and the concomitant inhibition of cytochrome oxidase activity in liver, brain, heart and blood. The detoxifying enzyme rhodanese was measured. The state of the sulfane sulfur pool was investigated by determination of the cyanide labile-sulfur levels. A clear correlation between rhodanese activity and sulfur content was obtained as a consequence of cyanide action. These results support the belief that rhodanese plays a fundamental role in the detoxification process of cyanide, in preventing cyanide reaching the target tissues.
Assuntos
Cianetos/intoxicação , Administração Oral , Animais , Cianetos/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Camundongos , Proteínas/metabolismo , Enxofre/metabolismo , Tiocianatos/metabolismo , Tiossulfato Sulfurtransferase/metabolismo , Fatores de TempoRESUMO
Tropical Spastic Paraparesis (TSP) in West African contries is countries is caused by combination of excess cyanide from the ingestion of Cassava and a deficiency of the sulphur-containing amino-acids required to detosify the cyanide. Free radical damage to long axons has also been reported to results in damage similar to that seen in Jamaican TSP. To investigate the possibility that these mechanisms may be responsible for Jamican TSP, venous blood from non-smoking blood donors and 22 patients with TSP were analysed for thiocyanate, superoxide dismutase and glutahione. Serum thiocyanate is an index of cyanide exposure. Superoxide dismutase protects against free radical damage, and glutathione in addition to rotecting against free radical damage is ana important sulphur-containing peptiae. Levels of thiocyanate in the patients with TSP were similar to those in control patients. Glutathione was elevated in all the patients, and superoxide dimutase activity was normal. The low levels of thiocyanate suggest that cyanide toxicity is not the primary cause of Jamaican TSP and, in any event, sufficient amounts of sulphur-containing amino-acids are present to detoxify cyanide. Free radical mechanisms ara also unlikely to be responsible for damage to the neurons in thes patients
Assuntos
Humanos , Paralisia/sangue , Superóxido Dismutase/sangue , Tiocianatos/sangue , Glutationa/sangue , Paralisia/etiologia , Cianetos/intoxicação , Radicais Livres , Jamaica , Espasticidade Muscular/sangueRESUMO
Tropical spastic paraparesis (TSP) in West African countries is caused by a combination of excess cyanide from the ingestion of cassava and a deficiency of the sulphur-containing amino-acids required to detoxify the cyanide. Free radical damage to long axons has also been reported to result in damage similar to that seen in Jamaican TSP. To investigate the possibility that these mechanisms may be responsible for Jamaican TSP, venous blood from non-smoking blood donors and 22 patients with TSP were analysed for thiocyanate, superoxide dismutase and glutathione. Serum thiocyanate is an index of cyanide exposure. Superoxide damage is an important sulphur-containing peptiae. Levels of thiocyanate in the patients with TSP were similar to those in control patients. Glutathione was elevated in all the patients, and a superoxide dismutase activity was normal. The low levels of thiocyanate suggest that cyanide toxicity is not the primary cause of Jamaican TSP and, in any event, sufficient amounts of sulphur-containing amino-acids are present to detoxify cyanide. Free radical mechanisms are also unlikely to be responsible for damage to the neurons in these patients (AU)
Assuntos
Humanos , Glutationa/sangue , Paralisia/sangue , Superóxido Dismutase/sangue , Tiocianatos/sangue , Cianetos/intoxicação , Radicais Livres , Espasticidade Muscular/sangue , Paralisia/etiologia , JamaicaRESUMO
Jamaican neuropathy, one of the earliest forms of tropical Spastic Paraparesis (TSP) to be described, is a major cause of neurological disability in Jamaica. Its cause has not been satisfactorily established, but chronic treponemal and, more recently, retroviral infections (HTLV-I) have been considered likely aetiological agents. Cyanide toxicity is regarded as the cause of TSP in certain West African countries. Free radicals have also been reported to cause damage to long axons. Although cassava and other cyanogenic items are used as staple items of diet in Jamaica, levels of this toxin have not been measured in Jamaican patients with TSP. The present study was therefore undertaken to determine whether (a) cyanide toxicity was associated with Jamaican TSP and (b) the levels of substances which protect against free radical damage were altered in these patients. Venous blood, obtained from twenty-two (22) patients with TSP, was analysed for thiocyanate (SCN). The levels of Cu/Zn superoxide dismutase, glutathione peroxidase and total glutathione, agents which protect against free radical damage, were also measured. Control samples were obtained from non-smoking blood donors matched for age. All patients and controls were questioned about their dietary habits. The levels of thiocyanate found in patients with the Jamaican form of TSP were similar to those found in control patients. Glutathione levels were elevated in all the patients. Superoxide dismutase activity was normal in all patients. The results obtained suggest that: (a) cyanide toxicity is not the primary cause of Jamaican TSP; (b) sufficient amounts of sulphur containing amino-acids are present to detoxify cyanide, even when present in high concentrations, and (c) free radical mechanisms are unlikely to be responsible for damage to the neurones in these TSP subjects (AU)