ArticleAlcoholism, clinical and experimental research2016
Therapeutic Benefits of Spleen Tyrosine Kinase Inhibitor Administration on Binge Drinking-Induced Alcoholic Liver Injury, Steatosis, and Inflammation in Mice.
Article in Alcoholism, clinical and experimental research, 2016. 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, 30 citations in OpenAlex.
- Paeoniflorin Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by SYK/SH3BP2 Signaling Pathway.Research (Washington, D.C.) · 2026Article
- Efficacy ofHeliyon · 2024Article
- Neuronal-specific methylome and hydroxymethylome analysis reveal significant loci associated with alcohol use disorder.Frontiers in genetics · 2024Article
- Neuronal-specific methylome and hydroxymethylome analysis reveal replicated and novel loci associated with alcohol use disorder.medRxiv : the preprint server for health sciences · 2023Article
- Hepatoprotective Effect of Albumin Peptide Fractions from Corn Germ Meal against Alcohol-Induced Acute Liver Injury in Mice.Foods (Basel, Switzerland) · 2023Article
- The spleen tyrosine kinase (SYK): A crucial therapeutic target for diverse liver diseases.Heliyon · 2022Review
- Protective Mechanism of Edible Food Plants against Alcoholic Liver Disease with Special Mention to Polyphenolic Compounds.Nutrients · 2021Review
- Alcohol Intake and Alcohol-SNP Interactions Associated with Prostate Cancer Aggressiveness.Journal of clinical medicine · 2021Article
- Alcoholic fatty liver disease inhibited the co-expression of Fmo5 and PPARα to activate the NF-κB signaling pathway, thereby reducing liver injury via inducing gut microbiota disturbance.Journal of experimental & clinical cancer research : CR · 2021Article
- The effect of spleen tyrosine kinase inhibitor R406 on diabetic retinopathy in experimental diabetic rats.International ophthalmology · 2020Article
- Hepatic protein-tyrosine phosphatase 1B disruption and pharmacological inhibition attenuate ethanol-induced oxidative stress and ameliorate alcoholic liver disease in mice.Redox biology · 2020Article
- Role of spleen tyrosine kinase in liver diseases.World journal of gastroenterology · 2020Review
- The protein tyrosine kinase SYK regulates the alternative p38 activation in liver during acute liver inflammation.Scientific reports · 2019Article
- Ginseng (Nutrients · 2018Article
- Abnormal neutrophil traps and impaired efferocytosis contribute to liver injury and sepsis severity after binge alcohol use.Journal of hepatology · 2018Article
- FXR and TGR5 Agonists Ameliorate Liver Injury, Steatosis, and Inflammation After Binge or Prolonged Alcohol Feeding in Mice.Hepatology communications · 2018Article
- Alcoholic liver disease.Nature reviews. Disease primers · 2018Review
- Using zebrafish to model liver diseases-Where do we stand?Current pathobiology reports · 2017Article
- Over expression of proteins that alter the intracellular signaling pathways in the cytoplasm of the liver cells forming Mallory-Denk bodies.Experimental and molecular pathology · 2017Article
- Baicalin Ameliorates Liver Injury Induced by Chronic plus Binge Ethanol Feeding by Modulating Oxidative Stress and Inflammation via CYP2E1 and NRF2 in Mice.Oxidative medicine and cellular longevity · 2017Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBinge drinking is increasingly recognized as an important cause of liver disease with limited therapeutic options for patients. Binge alcohol use, similar to chronic alcohol consumption, induces numerous deregulated signaling events that drive liver damage, steatosis, and inflammation. In this article, we evaluated the role of spleen tyrosine kinase (SYK), which modulates numerous signaling events previously identified linked in the development alcohol-induced liver pathology.
methodsA 3-day alcohol binge was administered to C57BL/6 female mice, and features of alcoholic liver disease were assessed. Some mice were treated daily with intraperitoneal injections of a SYK inhibitor (R406; 5 to 10 mg/kg body weight) or drug vehicle control. Liver and serum samples were collected and were assessed by Western blotting, biochemical, ELISA, electrophoretic mobility shift assays, real-time quantitative polymerase chain reaction, and histopathological analysis.
resultsWe found that binge drinking induced significant SYK activation (SYK(Y525/526) ) with no change in total SYK expression in the liver. Functional inhibition of SYK activation using a potent SYK inhibitor, R406, was associated with a significant decrease in alcohol-induced hepatic inflammation as demonstrated by decreased phospho-nuclear factor kappa beta (NF-κB) p65, NF-κB nuclear binding, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 mRNA in the liver. Compared to vehicle controls, SYK inhibitor treatment decreased alcohol binge-induced hepatocyte injury indicated by histology and serum alanine aminotransferase. Strikingly, SYK inhibitor treatment also resulted in a significant reduction in alcohol-induced liver steatosis.
conclusionsOur novel observations demonstrate the role of SYK, activation in the pathomechanism of binge drinking-induced liver disease highlighting SYK a potential multifaceted therapeutic target.
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