ArticleToxicology and applied pharmacology2020
Aldehyde dehydrogenase-2 activation decreases acetaminophen hepatotoxicity by prevention of mitochondrial depolarization.
Article in Toxicology and applied pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- Membrane-Targeted Consequences of Acetaminophen Toxicity and Off-Target Effects of Antimicrobial Peptides on Host Cell Membranes.International journal of molecular sciences · 2026Review
- Effects of ALDH2 gene expression on the oxidative stress‑mediated NF‑κB/mTOR pathway in ketamine‑induced cystitis.Molecular medicine reports · 2026Article
- Diurnal Regulation and Gene-Specific Vulnerability of Oxidative Alcohol-Metabolizing Enzymes to Circadian Disruption.International journal of molecular sciences · 2026Article
- Reactive oxygen species and peroxynitrite in acetaminophen-induced liver injury: Lipid peroxidation and ferroptosis-like cell death.Ferroptosis and oxidative stress · 2026Article
- Sirtuin 5-Mediated Desuccinylation of ALDH2 Alleviates Mitochondrial Oxidative Stress Following Acetaminophen-Induced Acute Liver Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- [Study based on the acetaldehyde dehydrogenase 2 gene polymorphism and acetaminophen-induced liver injury].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Article
- Platanosides, a Potential Botanical Drug Combination, Decrease Liver Injury Caused by Acetaminophen Overdose in Mice.Journal of natural products · 2022Review
- The role of Iron in lipid peroxidation and protein nitration during acetaminophen-induced liver injury in mice.Toxicology and applied pharmacology · 2022Article
- Sinapic acid ameliorates paracetamol-induced acute liver injury through targeting oxidative stress and inflammation.Molecular biology reports · 2022Article
- Structural library and visualization of endogenously oxidized phosphatidylcholines using mass spectrometry-based techniques.Nature communications · 2021Article
- Oxidant Stress and Acetaminophen Hepatotoxicity: Mechanism-Based Drug Development.Antioxidants & redox signaling · 2021Article
- Association between aldehyde dehydrogenase 2 gene rs671 G>A polymorphism and alcoholic liver cirrhosis in southern Chinese Hakka population.Journal of clinical laboratory analysis · 2021Article
- Ferroptosis and Acetaminophen Hepatotoxicity: Are We Going Down Another Rabbit Hole?Gene expression · 2021Review
- Augmented Liver Uptake of the Membrane Voltage Sensor Tetraphenylphosphonium Distinguishes Early Fibrosis in a Mouse Model.Frontiers in physiology · 2021Article
- Actually Seeing What Is Going on - Intravital Microscopy in Tissue Engineering.Frontiers in bioengineering and biotechnology · 2021Review
- Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Oxidative stress contributes to acetaminophen (APAP) hepatotoxicity. Since lipid peroxidation produces reactive aldehydes, we investigated whether activation of mitochondrial aldehyde dehydrogenase-2 (ALDH2) with Alda-1 decreases liver injury after APAP. Male C57BL/6 mice fasted overnight received Alda-1 (20 mg/kg, i.p.) or vehicle 30 min before APAP (300 mg/kg, i.p.). Blood and livers were collected 2 or 24 h after APAP. Intravital multiphoton microscopy of rhodamine 123 (Rh123) and propidium iodide (PI) fluorescence was conducted 6 h after APAP administration to detect mitochondrial polarization status and cell death. 4-Hydroxynonenal protein adducts were present in 0.1% of tissue area without APAP treatment but increased to 7% 2 h after APAP treatment, which Alda-1 blunted to 1%. Serum alanine and aspartate aminotransferases increased to 7594 and 9768 U/L at 24 h respectively, which decreased ≥72% by Alda-1. Alda-1 also decreased centrilobular necrosis at 24 h after APAP from 47% of lobular areas to 21%. N-acetyl-p-benzoquinone imine protein adduct formation and c-Jun-N-terminal kinase phosphorylation increased after APAP as expected, but Alda-1 did not alter these changes. Without APAP, no mitochondrial depolarization was detected by intravital microscopy. At 6 h after APAP, 62% of tissue area showed depolarization, which decreased to 33.5% with Alda-1. Cell death as detected by PI labeling increased from 0 to 6.8 cells per 30× field 6 h after APAP, which decreased to 0.6 cells by Alda-1. In conclusion, aldehydes are important mediators of APAP hepatotoxicity. Accelerated aldehyde degradation by ALDH2 activation with Alda-1 decreases APAP hepatotoxicity by protection against mitochondrial dysfunction.
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