Acute IP Administration of Sodium Fluoroacetate to Male Albino Rats; Protection by Monacetin Against Lethality of Sodium Fluoroacetate and 3-Cyclohexyl-1-(2-Fluoroethyl)-1-Nitrosourea (Cfnu) to Male Albino Rats

摘要

Several experiments, using rats, were designed to tet the hypothesis that the toxicity of 3-cyclohexyl-1-(2-fluoroethyl)-1-nitrosourea (CFNU) may be attributed, in part, to the metabolic release of free fluoroacetate radical and its subsequent toxicity. Monacetin is assumed to afford protection gainst fluoroacetate toxicity by providing a readily available supply of intracellular acetate ions to inhibit the lethal synthesis of fluoroacetate to fluorocitrate. Studies designed to demonstrate the protective action of monacetin aginst the toxicities of fluoroacetate and CFNU were performed. Determination of the acute intraperitoneal LD50 of sodium fluoroacetate was conducted in male albino rats using 10 animals per level and doses of 0.215, 0.464, 1.0, 2.15, 4.64, and 10 mg/kg. The intraperitoneal LD50 was calculated to be 1.58 mg/kg with confidence limits of 1.36 to 1.90 mg/kg and an LT50 of 0.11 day. Tremors or clonic convulsions were noted with doses of 1.0 mg/kg and higher. Results indicated that following CFNU monacetin prolonged life, although death still ensued. The design of the protection study was therefore modified to include 24 hourly injections of monacetin in an effort to demonstrate protection against death. Three dosage levels of monacetin - 0.15, 0.25, and 0.45 ml. were included in the modified design. Groups of 10 animals received monacetin alone (0.45 ml. intramuscularly), CFNU alone (21.5 mg/kg orally), or combinations of CFNU with the different levels of monacetin. Lengthening the monacetin regimen (which also increased the total dose) proved efficacious in affording protection against CFNU lethality. (Author)