Acetaminophen cytotoxicity in HepG2 cells is associated with a decoupling of glycolysis from the TCA cycle, loss of NADPH production, and suppression of anabolism

• Published in: Archives of toxicology Vol. 93; no. 2; pp. 341 - 353
• Main Authors: Behrends, Volker, Giskeødegård, Guro F., Bravo-Santano, Natalia, Letek, Michal, Keun, Hector C.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2019; Springer Nature B.V
• Subjects: Acetaminophen; Acetaminophen - toxicity; Acidosis; Amino acids; Analgesics; Apoptosis; Biocompatibility; Biomedical and Life Sciences; Biomedicine; Cell death; Cell lines; Cell Survival - drug effects; Citric Acid Cycle - drug effects; Cytotoxicity; Decoupling; Depletion; Drug Synergism; Environmental Health; Exposure; Fatty acids; Glutathione; Glutathione - metabolism; Glycine; Glycolysis; Glycolysis - drug effects; Hep G2 Cells; Hepatoma; Humans; In vivo methods and tests; Labeling; Lactates - metabolism; Lactic acid; Lactic acidosis; Liver; Liver cancer; Liver diseases; Metabolism; Metabolism - drug effects; Metabolites; Mitochondria; Molecular Toxicology; Monocarboxylic Acid Transporters - antagonists & inhibitors; Monocarboxylic Acid Transporters - metabolism; NADP; NADP - metabolism; Occupational Medicine/Industrial Medicine; Overdose; Oxidative stress; Pentose; Pharmacology/Toxicology; Pyrimidinones - toxicity; Reduction; Serine; Symporters - antagonists & inhibitors; Symporters - metabolism; Thiophenes - toxicity; Toxicity; Toxicity Tests; Tricarboxylic acid cycle; HepG2; Metabolomics; GC–MS; NMR; Isotopomer spectral analysis; Acetaminophen

Acetaminophen (APAP) is one of the most commonly used analgesics worldwide, and overdoses are associated with lactic acidosis, hepatocyte toxicity, and acute liver failure due to oxidative stress and mitochondrial dysfunction. Hepatoma cell lines typically lack the CYP450 activity to generate the re...