Metabolism and Effects on Endogenous Metabolism of Paracetamol (Acetaminophen) in a Porcine Model of Liver Failure.

ABSTRACT: The metabolic fate, toxicity, and effects on endogenous metabolism of paracetamol (acetaminophen, APAP) in 22 female Landrace cross large white pigs were evaluated in a model of acute liver failure (ALF). Anesthetized pigs were initially dosed at 250 mg/kg via an oroduodenal tube with APAP serum concentrations maintained above 300 mg/l using maintenance doses of 0.5-4 g/h until ALF. Studies were undertaken to determine both the metabolic fate of APAP and its effects on the endogenous metabolic phenotype of ALF in using 1H NMR spectroscopy. Increased concentrations of citrate combined with pre-ALF increases in circulating lactate, pyruvate, and alanine in plasma suggest mitochondrial dysfunction and a switch in hepatic energy metabolism to glycolysis in response to APAP treatment. A specifi

SUBMITTER: Dargue R 

PROVIDER: S-EPMC7197950 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature