Propranolol, a β-adrenoceptor antagonist, worsens liver injury in a model of non-alcoholic steatohepatitis
| العنوان: | Propranolol, a β-adrenoceptor antagonist, worsens liver injury in a model of non-alcoholic steatohepatitis |
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| المؤلفون: | Maelle Morgan, Barbara Sigalla, J Soeda, Chad McKee, Tania Roskams, Esra Asilmaz, Jude A. Oben, Nicoletta Sinelli |
| المصدر: | Biochemical and Biophysical Research Communications |
| بيانات النشر: | Elsevier BV, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Cirrhosis, Apoptosis, HPC, hepatic progenitor cell, Biochemistry, Choline, Mice, chemistry.chemical_compound, 0302 clinical medicine, Ethionine, Liver injury, 0303 health sciences, Stem Cells, Alanine Transaminase, Fas receptor, Propranolol, 3. Good health, medicine.anatomical_structure, Liver, 030220 oncology & carcinogenesis, Hepatocyte, PRZ, prazosin, NAFLD, non-alcoholic fatty liver disease, medicine.medical_specialty, Fas Ligand Protein, NASH, non-alcoholic steatohepatitis, Adrenergic beta-Antagonists, Biophysics, Biology, Article, 03 medical and health sciences, Internal medicine, Receptors, Adrenergic, beta, medicine, Animals, Molecular Biology, 030304 developmental biology, L-Lactate Dehydrogenase, Tumor Necrosis Factor-alpha, PRL, propranolol, OC, oval cell, Antagonist, Cell Biology, medicine.disease, Culture Media, Fatty Liver, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, chemistry, Sympathetic nervous system, Hepatocytes, Hepatic stellate cell, Steatohepatitis, Non-alcoholic fatty liver disease |
| الوصف: | Highlights • β-Blocker propranolol worsens liver injury in model of non-alcoholic steatohepatitis. • Mechanism of hepatic injury is via activation of apoptotic pathway in hepatocytes. • β-Blockers should be avoided or used with extreme caution in patients with NASH. Prazosin an α1-adrenoceptor (AR) antagonist has been shown to reduce liver injury in a mouse model of non-alcoholic steatohepatitis (NASH) and is suggested as a potential treatment of NASH especially given its concomitant anti-fibrotic properties. The effect however, of β-AR blockade in non-cirrhotic NASH is unknown and is as such investigated here. In the presence of the β-blocker propranolol (PRL), mice fed normal chow or a half methionine and choline deficient diet, supplemented with ethionine (HMCDE), to induce NASH, showed significantly enhanced liver injury, as evidenced by higher hepatic necrosis scores and elevated serum aminotransferases (ALT). Mechanistically, we showed that murine hepatocytes express α and β adrenoceptors; that PRL directly induces hepatocyte injury and death as evidenced by increased release of lactate dehydrogenase, FASL and TNF-α from hepatocytes in the presence of PRL; and that PRL activated the apoptotic pathway in primary hepatocyte cultures, as indicated by upregulation of Fas receptor and caspase-8 proteins. The β-AR antagonist PRL therefore appears to enhance liver injury through induction of hepatocyte death via the death pathway. Further studies are now required to extrapolate these findings to humans but meanwhile, β-AR antagonists should be avoided or used with caution in patients with non-cirrhotic NASH as they may worsen liver injury. |
| تدمد: | 0006-291X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f003a82453155f5ae4f332cad7b55123Test https://doi.org/10.1016/j.bbrc.2013.07.005Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f003a82453155f5ae4f332cad7b55123 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 0006291X |
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