RESUMEN
The effect of methoxyflurane anesthesia on allyl alcohol-induced hepatotoxicity and the metabolism of allyl alcohol was studied in male rats. Hepatotoxicity was assessed by the measurement of serum alanine aminotransferase activity and histopathological examination. Allyl alcohol-induced hepatotoxicity was enhanced when allyl alcohol (32 mg/kg) was administered 4 hr before or up to 8 days after a single 10-min exposure to methoxyflurane vapors. The possibility that methoxyflurane increases alcohol dehydrogenase-dependent oxidation of allyl alcohol to acrolein, the proposed toxic metabolite, was evaluated by measuring the rate of acrolein formation in the presence of allyl alcohol and liver cytosol. The effect of methoxyflurane on alcohol dehydrogenase activity in liver cytosol was also assessed by measuring the rate of NAD+ utilization in the presence of ethyl alcohol or allyl alcohol. Alcohol dehydrogenase activity and rate of acrolein formation were elevated in methoxyflurane-pretreated rats. The results suggest that a modest increase in alcohol dehydrogenase activity and rate of acrolein formation markedly enhances allyl alcohol-induced hepatotoxicity.
Asunto(s)
Acroleína/metabolismo , Aldehídos/metabolismo , Hígado/efectos de los fármacos , Metoxiflurano/farmacología , Propanoles , 1-Propanol/sangre , 1-Propanol/toxicidad , Acroleína/sangre , Acroleína/farmacología , Oxidorreductasas de Alcohol/metabolismo , Animales , Citosol/análisis , Hígado/citología , Hígado/enzimología , Masculino , Metoxiflurano/sangre , Unión Proteica , Ratas , Factores de TiempoAsunto(s)
Presión Intracraneal/efectos de los fármacos , Presión Intraocular/efectos de los fármacos , Metoxiflurano/farmacología , Respiración Artificial , Respiración/efectos de los fármacos , Acidosis Respiratoria/líquido cefalorraquídeo , Animales , Humor Acuoso/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Líquido Cefalorraquídeo/análisis , Líquido Cefalorraquídeo/efectos de los fármacos , Cloruros/sangre , Perros , Drenaje , Femenino , Masculino , Metoxiflurano/administración & dosificación , Concentración Osmolar , Potasio/sangreRESUMEN
MEthoxyflurane pulmonary inhalation administered to dogs, 2 ml/10kg/5 min, after 10 minutes caused a significant increase (13.3 mmHg) in intraocular pressure as well (6 mmHg) in venous pressure and a significant fall, of 23.3 mmHg, in arterial pressure and in respiratory frequency, of 3.2 per min and amplitude of 7.1 mm. On the other side, as acid-basic equilibrium alterations in blood, were observed a fall of 0.13 of pH and an increase of 18.3 mmHg of pCO2 and of 2.7 mEq/l of bicarbonate concentration.