Enoxaparin prevents fibrin accumulation in liver tissues and attenuates methotrexate-induced liver injury in rats
| العنوان: | Enoxaparin prevents fibrin accumulation in liver tissues and attenuates methotrexate-induced liver injury in rats |
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| المؤلفون: | Tamer M. Abdelghany, Mohamed S. Abdel-Bakky, Mohamed G Ewees, Abdel-Aziz H. Abdel-Aziz |
| المصدر: | Naunyn-Schmiedeberg's Archives of Pharmacology. 392:623-631 |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Pharmacology, Liver injury, Clotting factor, biology, General Medicine, medicine.disease, Fibrinogen, biology.organism_classification, Fibrin, Nitric oxide, Nitric oxide synthase, 03 medical and health sciences, chemistry.chemical_compound, Tissue factor, 030104 developmental biology, 0302 clinical medicine, chemistry, Enos, medicine, biology.protein, 030211 gastroenterology & hepatology, medicine.drug |
| الوصف: | Methotrexate (MTX) is a widely used drug for treatment of many malignant, rheumatic, and autoimmune diseases. However, hepatotoxicity remains one of the most serious side effects of MTX. The extrinsic coagulation pathway is activated after tissue injury through the release of tissue factor (TF) which activates a cascade of clotting factors including prothrombin and fibrinogen. Liver sinusoidal endothelial cells express endothelial nitric oxide synthase (eNOS) as a source for nitric oxide (NO) that serves as vasodilator and antithrombotic factor. In the current study, we tested the possible role of coagulation system activation in MTX-induced hepatotoxicity. Our results showed that single-dose administration of MTX significantly altered rat liver functions with concurrent turbulence in redox status. Immunofluorescence staining showed accumulation of fibrin in the periportal hepatocytes and downregulation of eNOS expression in hepatic endothelial and sinusoidal cells following MTX treatment. Moreover, MTX administration increased the expression of inducible nitric oxide synthase (iNOS) and NOSTRIN (eNOS traffic inducer) in the hepatic sinusoids. On the other hand, pre-treatment with enoxaparin rescued against MTX-induced liver injury with subsequent amelioration of liver redox status. Furthermore, it significantly prevented the effect of MTX on the expression of fibrin, iNOS, eNOS, and NOSTRIN. We concluded that liver tissue aggregation of the coagulation product, fibrin, may play a crucial role in the pathogenesis of MTX-induced liver injury. |
| تدمد: | 1432-1912 0028-1298 |
| DOI: | 10.1007/s00210-019-01618-1 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::4a754524fc03bcde099053738159300f https://doi.org/10.1007/s00210-019-01618-1 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi...........4a754524fc03bcde099053738159300f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321912 00281298 |
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| DOI: | 10.1007/s00210-019-01618-1 |