Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jan;126(1):86-91.
doi: 10.1111/bcpt.13304. Epub 2019 Sep 4.

Acetaminophen toxicity induces mitochondrial complex I inhibition in human liver tissue

Karoline Maise Chrøis  1 , Steen Larsen  1   2 , Julie Steen Pedersen  3 , Marte Opseth Rygg  3 , Astrid Elisabeth Bruun Boilsen  4 , Flemming Bendtsen  3 , Flemming Dela  1   5
Affiliations

Acetaminophen toxicity induces mitochondrial complex I inhibition in human liver tissue

Karoline Maise Chrøis et al. Basic Clin Pharmacol Toxicol. 2020 Jan.

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/L in 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.

Keywords: Acetaminophen (APAP); drug-induced liver injury; hepatotoxicity; mitochondrial respiratory capacity; overdose.

PubMed Disclaimer

References

REFERENCE

    1. Yoon E, Babar A, Choudhary M, Kutner M, Pyrsopoulos N. Acetaminophen-induced hepatotoxicity: a comprehensive update. J Clin Transl Hepatol. 2016;4(2):131-142.
    1. Shah AD, Wood DM, Dargan PI. Understanding lactic acidosis in paracetamol (acetaminophen) poisoning. Br J Clin Pharmacol. 2011;71(1):20-28.
    1. Davidson DG, Eastham WN. Acute liver necrosis following overdose of paracetamol. Br Med J. 1966;2(5512):497-499.
    1. Hinson JA, Roberts DW, James LP. Mechanisms of acetaminophen-induced liver necrosis. Handb Exp Pharmacol. 2010;196:369-405.
    1. McGill MR, Sharpe MR, Williams CD, Taha M, Curry SC, Jaeschke H. The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation. J Clin Invest. 2012;122(4):1574-1583.

LinkOut - more resources