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Review
. 2025 Apr;45(4):e16167.
doi: 10.1111/liv.16167. Epub 2024 Nov 15.

Novel Emerging Mechanisms in Acetaminophen (APAP) Hepatotoxicity

Alejandro Hionides-Gutierrez  1 , Naroa Goikoetxea-Usandizaga  2   3 , Carlos Sanz-García  1 , María L Martínez-Chantar  2   3 , Francisco Javier Cubero  1   3   4
Affiliations
Review

Novel Emerging Mechanisms in Acetaminophen (APAP) Hepatotoxicity

Alejandro Hionides-Gutierrez et al. Liver Int. 2025 Apr.

Abstract

Background: Drug-induced liver injury represents a critical public health issue, marked by unpredictable and potentially severe adverse reactions to medications, herbal products or dietary supplements.

Aims: Acetaminophen is notably a leading cause of hepatotoxicity, impacting over one million individuals worldwide.

Materials & methods: Extensive research has elucidated the intricate mechanisms driving APAP-induced liver injury, emphasising the significant roles of endoplasmic reticulum stress, oxidative stress, mitochondrial dysfunction and cell death.

Results: These insights pave the way for innovative therapeutic strategies, including the use of magnesium, bile acids, microbiota modulation and mesenchymal stem cells.

Discussion & conclusion: This review explores into these pathological mechanisms, proposing viable therapeutic interventions for patients suffering from APAP-induced liver injury.

Keywords: APAP‐induced liver injury; biliary acids; cell death; endoplasmic reticulum; magnesium transporters; microbiota; mitochondrial dysfunction; oxidative stress.

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