ArticleFood and chemical toxicology : an international journal published for the British Industrial Biological Research Association2019
The inhibitor of glycerol 3-phosphate acyltransferase FSG67 blunts liver regeneration after acetaminophen overdose by altering GSK3β and Wnt/β-catenin signaling.
Article in Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2019. 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, 30 citations in OpenAlex.
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- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Natural Products That Protect Against Acetaminophen Hepatotoxicity: A Call for Increased Rigor in Preclinical Studies of Dietary Supplements.Journal of dietary supplements · 2025Review
- The Role of Mechanistic Biomarkers in Understanding Acetaminophen Hepatotoxicity in Humans.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
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- MTCH2 cooperates with MFN2 and lysophosphatidic acid synthesis to sustain mitochondrial fusion.EMBO reports · 2024Article
- Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure.Acta pharmaceutica Sinica. B · 2024Article
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- EGR1 is crucial for the chlorogenic acid-provided promotion on liver regeneration and repair after APAP-induced liver injury.Cell biology and toxicology · 2023Article
- Hepatic pyruvate and alanine metabolism are critical and complementary for maintenance of antioxidant capacity and resistance to oxidative insult.Molecular metabolism · 2023Article
- Emodin Attenuates Acetaminophen-Induced Hepatotoxicity via the cGAS-STING Pathway.Inflammation · 2022Article
- Exogenous phosphatidic acid reduces acetaminophen-induced liver injury in mice by activating hepatic interleukin-6 signaling through inter-organ crosstalk.Acta pharmaceutica Sinica. B · 2021Article
- Mitochondrial Membrane Potential Drives Early Change in Mitochondrial Morphology After Acetaminophen Exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- The development and hepatotoxicity of acetaminophen: reviewing over a century of progress.Drug metabolism reviews · 2020Review
- Pre-treatment twice with liposomal clodronate protects against acetaminophen hepatotoxicity through a pre-conditioning effect.Liver research (Beijing, China) · 2020Article
- Lack of Multidrug Resistance-associated Protein 4 Prolongs Partial Hepatectomy-induced Hepatic Steatosis.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
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Authors and funding
6 authors at 3 institutions in 1 country.
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Abstract
Repair mechanisms after acetaminophen (APAP) hepatotoxicity are poorly understood. We recently discovered that phosphatidic acid (PA) increases in mice and humans after APAP overdose, and is critical for liver regeneration. Here, we hypothesized that PA inhibits glycogen synthase kinase-3β (GSK3β), a component of canonical Wnt/β-catenin signaling, after APAP overdose. To test that, we treated mice with 300 mg/kg APAP at 0 h followed by vehicle or 20 mg/kg of the glycerol 3-phosphate acyltransferase inhibitor FSG67 at 3, 24 and 48 h. Some mice also received the GSK3 inhibitor L803-mts. Blood and liver were collected at multiple time points. Consistent with our earlier results, FSG67 did not affect toxicity (ALT, histology), APAP bioactivation (total glutathione), or oxidative stress (oxidized glutathione), but did reduce expression of proliferating cell nuclear antigen (PCNA) at 52 h. We then measured GSK3β phosphorylation and found it was dramatically decreased by FSG67 at 24 h, before PCNA dropped. Expression of cyclin D1, downstream of Wnt/β-catenin, was also reduced. To determine if the effect of FSG67 on GSK3β is important, we treated mice with FSG67 and L803-mts after APAP. Importantly, L803-mts rescued hepatocyte proliferation and survival. Our data indicate PA and lysoPA may support recovery after APAP overdose by inhibiting GSK3β.
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