ArticleToxicon : official journal of the International Society on Toxinology2017
Microcystin-LR induced liver injury in mice and in primary human hepatocytes is caused by oncotic necrosis.
Article in Toxicon : official journal of the International Society on Toxinology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 44 citations in OpenAlex.
- Novel insights into cyanobacterial (microcystins) neurotoxicity in rats: hepatic encephalopathy.Archives of toxicology · 2026Article
- Female reproductive impacts of emerging cyanobacterial harmful algal bloom toxins.The Journal of reproduction and development · 2026Review
- Hepatocyte-Derived Extracellular Vesicles Deliver miR-328-3p to Trigger PP2A-B56δ-Mediated p-NLRP3Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Unraveling the Role of Microcystin-LR in Ferroptosis and Sepsis Pathogenesis: A Comprehensive Review.Biomolecules · 2025Review
- Microcystin-LR and its health impacts: Chemistry, transmission routes, mechanisms of toxicity and target organs.Toxicology reports · 2025Review
- Short-term ingestion of sublethal microcystin levels disrupts stress response in male mice.Frontiers in endocrinology · 2025Article
- Aerosolized Harmful Algal Bloom Toxin Microcystin-LR Induces Type 1/Type 17 Inflammation of Murine Airways.Toxins · 2024Article
- The cytotoxicity of microcystin-LR: ultrastructural and functional damage of cells.Archives of toxicology · 2024Review
- Morchella Effectively Removes Microcystins Produced by Microcystis aeruginosa.Microbes and environments · 2024Article
- Hepatic NLRP3-Derived Hsp70 Binding to TLR4 Mediates MASLD to MASH Progression upon Inhibition of PP2A by Harmful Algal Bloom Toxin Microcystin, a Second Hit.International journal of molecular sciences · 2023Article
- Purification and Activity of the Second Recombinant Enzyme for Biodegrading Linearized Microcystins byToxins · 2023Article
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- Properties of CaOEnvironmental science and pollution research international · 2020Article
- CD40 Receptor Knockout Protects against Microcystin-LR (MC-LR) Prolongation and Exacerbation of Dextran Sulfate Sodium (DSS)-Induced Colitis.Biomedicines · 2020Article
- Effects of Chronic Exposure to Microcystin-LR on Kidney in Mice.International journal of environmental research and public health · 2019Article
- Exogenous PP2A inhibitor exacerbates the progression of nonalcoholic fatty liver disease via NOX2-dependent activation of miR21.American journal of physiology. Gastrointestinal and liver physiology · 2019Article
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Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Microcystins are a group of toxins produced by freshwater cyanobacteria. Uptake of microcystin-leucine arginine (MC-LR) by organic anion transporting polypeptide 1B2 in hepatocytes results in inhibition of protein phosphatase 1A and 2A, and subsequent cell death. Studies performed in primary rat hepatocytes demonstrate prototypical apoptosis after MC-LR exposure; however, no study has directly tested whether apoptosis is critically involved in vivo in the mouse, or in human hepatocytes. MC-LR (120 μg/kg) was administered to C57BL/6J mice and cell death was evaluated by alanine aminotransferase (ALT) release, caspase-3 activity in the liver, and histology. Mice exposed to MC-LR had increases in plasma ALT values, and hemorrhage in the liver, but no increase in capase-3 activity in the liver. Pre-treatment with the pan-caspase inhibitor z-VAD-fmk failed to protect against cell death measured by ALT, glutathione depletion, or hemorrhage. Administration of MC-LR to primary human hepatocytes resulted in significant toxicity at concentrations between 5 nM and 1 μM. There were no elevated caspase-3 activities and pretreatment with z-VAD-fmk failed to protect against cell death in human hepatocytes. MC-LR treated human hepatocytes stained positive for propidium iodide, indicating membrane instability, a marker of necrosis. Of note, both increases in PI positive cells, and increases in lactate dehydrogenase release, occurred before the onset of complete actin filament collapse. In conclusion, apoptosis does not contribute to MC-LR-induced cell death in the in vivo mouse model or in primary human hepatocytes in vitro. Thus, targeting necrotic cell death mechanisms will be critical for preventing microcystin-induced liver injury.
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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.