Disease relevance of ethanehydrazide

• Toxicity experiments carried out with rapid and slow acetylator rabbits showed that the slow acetylators exhibited greater susceptibility to lethal central nervous system actions of isoniazid and its metabolite, monoacetylhydrazine [1].

High impact information on ethanehydrazide

• These data demonstrate that the mechanistic information obtained in animal models cannot be applied readily in clinical practice and that measurable inhibition of acetylhydrazine metabolism to prevent isoniazid liver injury does not occur after administration of therapeutic doses of cimetidine to patients [2].
• Studies in rats indicate that the metabolic activation of acetylhydrazine, a metabolite of isoniazid, is a critical determinant of the hepatotoxicity of isoniazid [3].
• Treatment of posttranslationally 3H-labeled alpha-tubulin with hydrazine yields radioactive acetylhydrazine, indicating that the moiety involved in posttranslational modification is an acetyl group [4].
• The incubation of isolated hepatocytes with isoniazid or acetyl-hydrazine reduced by 20-25% the intracellular GSH content, while a 50% decrease in GSH was present in the cells exposed to iproniazid and isopropyl-hydrazine [5].
• The m-chlorobenzoyl derivatives of isoniazid, acetylhydrazine and the internal standard propionylhydrazine were prepared, separated on a RP-18 column and detected at 220 nm [6].

Chemical compound and disease context of ethanehydrazide

• Using a model of INH-induced hepatotoxicity in rabbits, in which INH-induced hepatotoxicity manifests as hepatic necrosis, hepatic steatosis (hepatic fat accumulation) and hypertriglyceridaemia (elevated plasma triglycerides), we compared the severity of these measures of toxicity with plasma levels of INH, acetylhydrazine and hydrazine [7].

Biological context of ethanehydrazide

• Comparison of urinary metabolites of isoniazid at two dose levels indicated that acetylation of acetylhydrazine produced as a metabolite may be inhibited by the parent drug [8].
• When acetyl-INH was administered, covalent hepatic protein binding of the acetyl moiety was greater in the rabbit than the rat, but the opposite was observed when acetylhydrazine was administered [9].

Associations of ethanehydrazide with other chemical compounds

• The acetylation of acetylhydrazine to diacetylhydrazine was found to be dose-dependent and to be inhibited by coadministered isoniazid and p-aminosalicylic acid [10].
• Determination of isoniazid, acetylisoniazid, acetylhydrazine and diacetylhydrazine in biological fluids by high-performance liquid chromatography [6].

Gene context of ethanehydrazide

• When this antimode was used, the mean apparent kinetic variables of INH and acetyl INH estimated from the plasma concentration-time data and the mean values for the 24-h urinary amount of INH and its metabolites, except for monoacetylhydrazine (P less than 0.05), did not significantly differ between the rapid acetylators of SLE and control groups [11].

References