ArticleFree radical biology & medicine2015
M1 muscarinic receptors modify oxidative stress response to acetaminophen-induced acute liver injury.
Article in Free radical biology & medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Selective modulation of murine intestinal MAmerican journal of physiology. Cell physiology · 2026Article
- Vitamin K1 attenuates acetaminophen-induced ferroptotic hepatic damage in mice via targeting keap1/Nrf2/HO-1 pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Roles of the Keap1/Nrf2 pathway and mitophagy in liver diseases.Journal of Zhejiang University. Science. B · 2025Review
- Mesenchymal Stem Cells with Simultaneous Overexpression of GPX3 and CD47 for the Treatment of Drug-Induced Acute Liver Injury.Veterinary sciences · 2025Article
- Investigation of the General Molecular Mechanisms of Gallic Acid via Analyses of Its Transcriptome Profile.International journal of molecular sciences · 2024Article
- Hepatotoxicity of antipsychotics: an exploratory pharmacoepidemiologic and pharmacodynamic study integrating FAERS data andFrontiers in psychiatry · 2024Article
- Muscarinic receptor agonist-induced βPix binding to β-catenin promotes colon neoplasia.Scientific reports · 2023Article
- The molecular mechanisms of acetaminophen-induced hepatotoxicity and its potential therapeutic targets.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Article
- Herbal Therapy for the Treatment of Acetaminophen-Associated Liver Injury: Recent Advances and Future Perspectives.Frontiers in pharmacology · 2020Review
- Preventive action of benztropine on platinum-induced peripheral neuropathies and tumor growth.Acta neuropathologica communications · 2019Article
- Article
- Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions.Redox biology · 2018Review
- Progressive changes in detrusor function and micturition patterns with chronic bladder ischemia.Investigative and clinical urology · 2016Article
- Data regarding M1 muscarinic receptor-mediated modulation of hepatic catalase activity in response to oxidative stress.Data in brief · 2016Article
- Salvianolic Acid B Prevents Iodinated Contrast Media-Induced Acute Renal Injury in Rats via the PI3K/Akt/Nrf2 Pathway.Oxidative medicine and cellular longevity · 2016Article
- M1 Muscarinic Receptor Deficiency Attenuates Azoxymethane-Induced Chronic Liver Injury in Mice.Scientific reports · 2015Article
- Withaferin-A Reduces Acetaminophen-Induced Liver Injury in Mice.Biochemical pharmacology · 2015Article
- Pathophysiological significance of c-jun N-terminal kinase in acetaminophen hepatotoxicity.Expert opinion on drug metabolism & toxicology · 2015Review
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10 authors.
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Abstract
The role of muscarinic receptor subtypes in modulating acute liver injury is unknown. We detected M1 muscarinic receptor (M1R) expression in human and murine hepatocytes, and investigated the consequences of M1R deficiency on acute liver injury in vivo and inhibiting M1R activation on hepatocyte injury in vitro. Age-matched wild-type (WT) and M1R-deficient (Chrm1(-/-)) male mice were injected intraperitoneally with 200mg/kg acetaminophen (APAP) and euthanized 0, 2, 4, 16, 24, and 36h later. Biochemical and histological parameters indicated that liver injury peaked within 16h after APAP treatment and resolved by 24h. Compared to WT, M1R-deficient mice had reduced intrahepatic hemorrhage and hepatocyte necrosis, reflected by an attenuated rise in serum alanine aminotransferase levels. Livers of M1R-deficient mice showed reduced hepatocyte DNA fragmentation and attenuated expression of injury cytokines (Il-1α, Il-1β, Il-6, and Fasl). In all mice hepatic glutathione levels decreased after APAP injection, but they recovered more quickly in M1R-deficient mice. During the course of APAP-induced liver injury in M1R-deficient compared to WT mice, hepatic Nrf-2, Gclc, and Nqo1 expressions increased and nitrotyrosine generation decreased. APAP metabolic pathways were not altered by M1R deficiency; expression of hepatic Cyp2e1, Cyp1a2, Cyp3a11, Cyp3a13, Car, and Pxr was similar in Chrm1(-/-) and WT mice. Finally, treatment of murine AML12 hepatocytes with a novel M1R antagonist, VU0255035, attenuated H2O2-induced oxidative stress, prevented GSH depletion, and enhanced viability. We conclude that M1R modify hepatocyte responses to oxidative stress and that targeting M1R has therapeutic potential for toxic liver injury.
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