الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 164 |  |  |
| | | from | 164 | | |
Abstract
Autoimmune hepatitis is an inflammatory condition with an increasing frequency, resulting in a significant worldwide burden and a substantial risk to human life. AIH is a significant immune-mediated inflammatory hepatic condition characterized by extensive infiltration of inflammatory cells and cytokines into the hepatic tissue. This liver inflammatory syndrome is linked with increased serum transaminases and severe hepatic necrosis and apoptosis, which can lead to cirrhosis and failure. The aim of the study was to establish a model of AIH in mice and to evaluate the potential protective influence of celecoxib against ConA-induced AIH and to underly their possible mechanisms. Male albino mice were admisterated celecoxib orally for seven consecutive days by 30 and 60 mg/kg. On the day eight, mice were injected with ConA (20 mg/kg, iv) via the retro-orbital venous plexus under light ether anesthesia 6 h before sacrifice. At the end of the experiment blood samples were collected and serum was used for biochemical measurments (ALT and AST). Moreover, liver tissue was collected for determination of oxidative stress biomarkers, apoptotic and autophagy markers, histopathological and immunohistochemical examination. The results can be summarized as follows: Pretreatment with celecoxib significantly and dose-dependently protected against Con A-induced AIH. Administration of celecoxib in high dose 60 mg/kg was highly effective in decreasing the increase of ALT, AST, IL1β, TNF-α, COX-2, p-AKT/AKT ratio, apoptotic markers (caspase-3 and p-JNK) and autophagy markers (Beclin-1 and LC3II). However, in small dose 30 mg/kg there was significant effect noticed in some measured parameters. Furthermore, celecoxib attenuated ConA-induced oxidative stress as revealed by significant decreasing of MDA and NO hepatic contents and restoring of SOD and GSH contents in addition to significant increasing of Nrf2 and HO-1 hepatic contents. Histopathology examination of control group revealed normal histopathological structure. Whereas widespread necrosis in the majority of ConA-treated mice group. Treatment with celecoxib (60 mg/kg) for seven days prior to ConA injection significantly decreased these changes induced by ConA and improved histological picture.