ArticleRedox biology2017
Inhibition of Drp1 protects against senecionine-induced mitochondria-mediated apoptosis in primary hepatocytes and in mice.
Article in Redox biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Research trends of mitochondrial dysfunction in hepatic fibrosis: a bibliometric analysis.Frontiers in physiology · 2026Pooled it
- Nutritional Components and Anti-Alcoholic Liver Disease Activity of Selenium-EnrichedFoods (Basel, Switzerland) · 2026Article
- Pyrrolizidine Alkaloid-Induced Hepatotoxicity: A Narrative Review on Molecular Mechanisms and Detoxification Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Schisandrol B protects against lithocholic acid-induced cholestatic liver injury in mice through mitochondrial biogenesis.Chinese medicine · 2026Article
- The pathogenesis of liver fibrosis in Wilson's disease: hepatocyte injury and regulation mediated by copper metabolism dysregulation.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Hepatic Sinusoidal Obstruction Syndrome Induced by Pyrrolizidine Alkaloids fromMolecules (Basel, Switzerland) · 2026Review
- Mitochondrial dysfunction in Alzheimer's disease and related sex differences.Frontiers in aging neuroscience · 2026Review
- Scutellarin suppresses Mycobacterium tuberculosis-induced pyroptosis in macrophages by inhibiting the HIF-1α-mediated Warburg effect.Redox report : communications in free radical research · 2025Article
- The pyrrolizidine alkaloid lasiocarpine impairs cell cycle progression in vitro.Archives of toxicology · 2025Article
- Chlorogenic acid attenuates pyrrolizidine alkaloid-induced liver injury through modulation of the SIRT1/FXR signaling pathway.Chinese medicine · 2025Article
- The Essential Role of Mitochondrial Dynamics in Viral Infections.International journal of molecular sciences · 2025Review
- Empagliflozin in diabetic cardiomyopathy: elucidating mechanisms, therapeutic potentials, and future directions.Molecular biology reports · 2025Review
- Receptor-Interacting Protein Kinase 3-Mediated Modulation of Endothelial Cell Necroptosis and Mitochondrial Dysfunction through AMPK/Drp1 Signaling Pathway: Insights into the Pathophysiological Mechanisms of Lipopolysaccharide-Induced Acute Lung Injury.International journal of medical sciences · 2025Article
- Functional metabolomics characterizes the contribution of farnesoid X receptor in pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome.Archives of toxicology · 2024Article
- Article
- Epigallocatechin gallate attenuated high glucose-induced pancreatic beta cell dysfunction by modulating DRP1-mediated mitochondrial apoptosis pathways.Scientific reports · 2024Article
- Targeting Mitochondrial Dysfunction and Reactive Oxygen Species for Neurodegenerative Disease Treatment.International journal of molecular sciences · 2024Review
- Hexavalent-Chromium-Induced Disruption of Mitochondrial Dynamics and Apoptosis in the Liver via the AMPK-PGC-1α Pathway in Ducks.International journal of molecular sciences · 2023Article
- Mitochondria-lysosome-related organelles mediate mitochondrial clearance during cellular dedifferentiation.Cell reports · 2023Article
- Peroxisome proliferator-activated receptor α agonist induces mouse hepatomegaly through the spatial hepatocyte enlargement and proliferation.Acta pharmacologica Sinica · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Pyrrolizidine alkaloids (PAs) are a group of compounds found in various plants and some of them are widely consumed in the world as herbal medicines and food supplements. PAs are potent hepatotoxins that cause irreversible liver injury in animals and humans. However, the mechanisms by which PAs induce liver injury are not clear. In the present study, we determined the hepatotoxicity and molecular mechanisms of senecionine, one of the most common toxic PAs, in primary cultured mouse and human hepatocytes as well as in mice. We found that senecionine administration increased serum alanine aminotransferase levels in mice. H&E and TUNEL staining of liver tissues revealed increased hemorrhage and hepatocyte apoptosis in liver zone 2 areas. Mechanistically, senecionine induced loss of mitochondrial membrane potential, release of mitochondrial cytochrome c as well as mitochondrial JNK translocation and activation prior to the increased DNA fragmentation and caspase-3 activation in primary cultured mouse and human hepatocytes. SP600125, a specific JNK inhibitor, and ZVAD-fmk, a general caspase inhibitor, alleviated senecionine-induced apoptosis in primary hepatocytes. Interestingly, senecionine also caused marked mitochondria fragmentation in hepatocytes. Pharmacological inhibition of dynamin-related protein1 (Drp1), a protein that is critical to regulate mitochondrial fission, blocked senecionine-induced mitochondrial fragmentation and mitochondrial release of cytochrome c and apoptosis. More importantly, hepatocyte-specific Drp1 knockout mice were resistant to senecionine-induced liver injury due to decreased mitochondrial damage and apoptosis. In conclusion, our results uncovered a novel mechanism of Drp1-mediated mitochondrial fragmentation in senecionine-induced liver injury. Targeting Drp1-mediated mitochondrial fragmentation and apoptosis may be a potential avenue to prevent and treat hepatotoxicity induced by PAs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.