Abstract
Medium chain dicarboxylic aciduria has been induced in fasted rats by 2-tetradecyloxiranecarboxylate (TDOC), a known inhibitor of carnitine: palmitoyltransferase I. Administration to fasted rats in dosages of 5 mg/kg or 30 mg/kg of body weight each day caused supression-in the expected fasting-induced enhancement of 3-hydroxybutyric acid excretion and an increase in the excretion of palmitic acid in the first 24 hour period of fasting, implying an in vivo inhibition of the mitochondrial β-oxidation of long chain fatty acids. Along with these effects, excretions of two medium chain dicarboxylic acids-sebacic and suberic acids-were also induced in the fasted rats. A similar dicarboxylic aciduria was found in non-fasted rats given 30 mg/kg of this inhibitor. Liver histology revealed microvesicular fatty change in the fasted, TDOC-loaded animals. The TDOC-induced medium chain dicarboxylic aciduria in rat is an effective model for correlation to impaired mitochondrial, β-oxidation in human.
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