Acetaminophen toxicity induces mitochondrial complex I inhibition in human liver tissue.

PMID: 

Basic Clin Pharmacol Toxicol. 2019 Aug 12. Epub 2019 Aug 12. PMID: 31403256

Abstract Title: 

Acetaminophen toxicity induces mitochondrial complex I inhibition in human liver tissue.

Abstract: 

Acetaminophen (APAP) is used worldwide and is regarded as safe in therapeutic concentrations but can cause acute liver failure in higher doses. High doses of APAP have been shown to inhibit complex I and II mitochondrial respiratory capacity in mouse hepatocytes, but human studies are lacking. Here, we studied mitochondrial respiratory capacity in human hepatic tissue ex vivo with increasing doses of APAP. Hepatic biopsies were obtained from 12 obese patients who underwent a roux-en-Y gastric bypass (RYGB) or a sleeve gastrectomy surgery. Mitochondrial respiration was measured by high-resolution respirometry. Therapeutic concentrations (≤0.13 mmol·l) of APAP did not inhibit state 3 complex I-linked respiration. APAP concentrations of≥2.0 mmol·lin the medium significantly reduced hepatic mitochondrial respiration in a dose-dependent manner. Complex II-linked mitochondrial respiration was not inhibited by APAP. We conclude that the mitochondrial respiratory capacity is affected by a hepato-toxic effect of APAP, which involved complex I, but not complex II. This article is protected by copyright. All rights reserved.

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