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العنوان
Management of concanavalin A induced liver injury by inhibition of more than one inflammatory pathway /
المؤلف
Elshal, Mahmoud Ali Mahmoud.
هيئة الاعداد
باحث / محمود على محمود الشال
مشرف / طارق مصطفى إبراهيم
مشرف / نشوى محمد أبو السعد
مناقش / ناجح أحمد المهدى
مناقش / منار احمد نادر
الموضوع
Concanavalin A. Liver - Diseases.
تاريخ النشر
2019.
عدد الصفحات
108 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
الصيدلة ، علم السموم والصيدلانيات (المتنوعة)
الناشر
تاريخ الإجازة
20/1/2020
مكان الإجازة
جامعة المنصورة - كلية الصيدلة - الأدوية والسموم
الفهرس
Only 14 pages are availabe for public view

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from 128

Abstract

Despite of the scientific progress in the field of liver disorders, immune-mediated hepatitis as autoimmune hepatitis remains a major clinical challenge with limited and non-specific therapeutic options where, immunosuppressants and liver transplantation represent the main current treatment while, specific immune targets as a therapeutic option are still limited. The present study was conducted to investigate potential protecting effects of all-trans retinoic acid and/or etanercept on experimentally-induced immune-mediated hepatitis, where the potential anti-inflammatory effects of tested drugs on concanavalin A-induced immune-mediated hepatitis. Experimental design: mice were randomly divided into five groups as follows: Control group (n=15): received no treatments but only drugs vehicles, ConA group (n=15): mice were injected by ConA [15 mg/kg 0.5% w/v in sterile 0.9% sodium chloride solution, 3 ml/kg, once i.v, via the retro-orbital venous plexus under light ether anesthesia], ConA + RA group (n=15): received ConA as indicated plus RA solution [35 mg/kg, 0.35% w/v in DMSO/olive oil mixture (40/60), 10 ml/kg i.p] 16 hours before ConA, ConA + ET group (n=15): received ConA as indicated plus etanercept solution [15 mg/kg, 0.25% w/v in sterile water for injection, 6 ml/kg i.p] 30 min before ConA, and ConA + RA + Etanercept (n=15): received ConA as indicated below in addition to RA solution plus ET solution as described. The development of hepatic inflammation was assessed mainly by employing hepatic histopathological examination, assessment of liver function and lipid peroxidation biomarker, assessment of cytokines level in hepatic tissue as tumor necrosis factor alpha, monocyte chemoattractant protein-1, interleukin-4, and interleukin-10 and also neutrophils and CD4+ T cells infiltration to liver. Pretreatment with all-trans retinoic acid and/or etanercept attenuated ConA-induced immune-mediated hepatitis progression. This was indicated mainly by decreasing necro-inflammatory score as revealed by examined liver sections histopathologically. The improvement was ensured by lowering elevated liver function biomarkers, reducing lipid peroxidation biomarker, decreased hepatic levels of tumor necro.