ArticleHepatology (Baltimore, Md.)2017
Pentamidine blocks hepatotoxic injury in mice.
Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 19 citations in OpenAlex.
- A Novel Bifunctional Fusion Protein (Anti-IL-17A-sST2) Protects against Acute Liver Failure, Modulating the TLR4/MyD88 Pathway and NLRP3 Inflammasome Activation.Biomedicines · 2024Article
- The Elk-3 target Abhd10 ameliorates hepatotoxic injury and fibrosis in alcoholic liver disease.Communications biology · 2023Article
- Role of liensinine in sensitivity of activated macrophages to ferroptosis and in acute liver injury.Cell death discovery · 2023Article
- HBx facilitates ferroptosis in acute liver failure via EZH2 mediated SLC7A11 suppression.Journal of biomedical science · 2021Article
- A new perspective of triptolide-associated hepatotoxicity: the relevance of NF-Acta pharmaceutica Sinica. B · 2020Article
- Sensitization of colorectal cancer to irinotecan therapy by PARP inhibitor rucaparib.Investigational new drugs · 2019Article
- Human amniotic mesenchymal stromal cells alleviate acute liver injury by inhibiting the pro-inflammatory response of liver resident macrophage through autophagy.Annals of translational medicine · 2019Article
- Spermine Alleviates Acute Liver Injury by Inhibiting Liver-Resident Macrophage Pro-Inflammatory Response Through ATG5-Dependent Autophagy.Frontiers in immunology · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Toxin-induced liver diseases lack effective therapies despite increased understanding of the role factors such as an overactive innate immune response play in the pathogenesis of this form of hepatic injury. Pentamidine is an effective antimicrobial agent against several human pathogens, but studies have also suggested that this drug inhibits inflammation. This potential anti-inflammatory mechanism of action, together with the development of a new oral form of pentamidine isethionate VLX103, led to investigations of the effectiveness of this drug in the prevention and treatment of hepatotoxic liver injury. Pretreatment with a single injection of VLX103 in the d-galactosamine (GalN) and lipopolysaccharide (LPS) model of acute, fulminant liver injury dramatically decreased serum alanine aminotransferase levels, histological injury, the number of terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL)-positive cells and mortality compared with vehicle-injected controls. VLX103 decreased GalN/LPS induction of tumor necrosis factor (TNF) but had no effect on other proinflammatory cytokines. VLX103 prevented the proinflammatory activation of cultured hepatic macrophages and partially blocked liver injury from GalN/TNF. In GalN/LPS-treated mice, VLX103 decreased activation of both the mitochondrial death pathway and downstream effector caspases 3 and 7, which resulted from reduced c-Jun N-terminal kinase activation and initiator caspase 8 cleavage. Delaying VLX103 treatment for up to 3 hours after GalN/LPS administration was still remarkably effective in blocking liver injury in this model. Oral administration of VLX103 also decreased hepatotoxic injury in a second more chronic model of alcohol-induced liver injury, as demonstrated by decreased serum alanine and aspartate aminotransferase levels and numbers of TUNEL-positive cells.
conclusionVLX103 effectively decreases toxin-induced liver injury in mice and may be an effective therapy for this and other forms of human liver disease. (Hepatology 2017;66:922-935).
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