ArticleScientific reports2021
Clodronate, an inhibitor of the vesicular nucleotide transporter, ameliorates steatohepatitis and acute liver injury.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 23 citations in OpenAlex.
- In vivo visualization of cardiac extracellular adenosine dynamics and its pharmacological modulation in zebrafish heart failure models.Scientific reports · 2026Article
- The role and therapeutic potential of purinergic signaling pathway in metabolic syndrome-related atherosclerosis.Purinergic signalling · 2026Review
- Clodronate: The Influence on ATP Purinergic Signaling.Current rheumatology reviews · 2026Review
- Exocytosed ATP as a therapeutic target for inflammatory and metabolic diseases.Frontiers in pharmacology · 2026Review
- Article
- Alterations in gut microbiota and insights into the colonic function by clodronate: a study using short bowel syndrome rat model.Pediatric surgery international · 2025Article
- The Role of Solute Carrier Family Transporters in Hepatic Steatosis and Hepatic Fibrosis.Journal of clinical and translational hepatology · 2025Review
- Favorable inhibitory effect of clodronate on hepatic steatosis in short bowel syndrome model rats.Pediatric surgery international · 2024Article
- RANK-RANKL-OPG Axis in MASLD: Current Evidence Linking Bone and Liver Diseases and Future Perspectives.International journal of molecular sciences · 2024Review
- Hepatic extracellular ATP/adenosine dynamics in zebrafish models of alcoholic and metabolic steatotic liver disease.Scientific reports · 2024Article
- Anti-osteoporotic treatments in the era of non-alcoholic fatty liver disease: friend or foe.Frontiers in endocrinology · 2024Review
- P2Y2 purinergic receptor gene deletion protects mice from bacterial endotoxin and sepsis-associated liver injury and mortality.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Hepatocyte CYR61 polarizes profibrotic macrophages to orchestrate NASH fibrosis.Science translational medicine · 2023Article
- SLC17A9-PTHLH-EMT axis promotes proliferation and invasion of clear renal cell carcinoma.iScience · 2023Article
- Resident macrophages of the lung and liver: The guardians of our tissues.Frontiers in immunology · 2022Review
- Is the vesicular nucleotide transporter a molecular target of eicosapentaenoic acid?Frontiers in pharmacology · 2022Article
- Rheb Promotes Triglyceride Secretion and Ameliorates Diet-Induced Steatosis in the Liver.Frontiers in cell and developmental biology · 2022Article
- Quinacrine is not a vital fluorescent probe for vesicular ATP storage.Purinergic signalling · 2021Article
- Synapomorphic features of hepatic and pulmonary vasculatures include comparable purinergic signaling responses in host defense and modulation of inflammation.American journal of physiology. Gastrointestinal and liver physiology · 2021Review
- Purinergic Signaling in Liver Pathophysiology.Frontiers in endocrinology · 2021Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The vesicular nucleotide transporter (VNUT) is responsible for the vesicular storage and release of ATP from various ATP-secreting cells, and it plays an essential role in purinergic signaling. Although extracellular ATP and its degradation products are known to mediate various inflammatory responses via purinoceptors, whether vesicular ATP release affects steatohepatitis and acute liver injury is far less understood. In the present study, we investigated the effects of clodronate, a potent and selective VNUT inhibitor, on acute and chronic liver inflammation in mice. In a model of methionine/choline-deficient diet-induced non-alcoholic steatohepatitis (NASH), the administration of clodronate reduced hepatic inflammation, fibrosis, and triglyceride accumulation. Clodronate also protected mice against high-fat/high-cholesterol diet-induced steatohepatitis. Moreover, prophylactic administration of clodronate prevented D-galactosamine and lipopolysaccharide-induced acute liver injury by reducing inflammatory cytokines and hepatocellular apoptosis. In vitro, clodronate inhibited glucose-induced vesicular ATP release mediated by VNUT and reduced the intracellular level and secretion of triglycerides in isolated hepatocytes. These results suggest that VNUT-dependent vesicular ATP release plays a crucial role in the recruitment of immune cells, cytokine production, and the aggravation of steatosis in the liver. Pharmacological inhibition of VNUT may provide therapeutic benefits in liver inflammatory disorders, including NASH and acute toxin-induced injury.
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