الفهرس 
List of abbreviations
Liver InflammationOnly 14 pages are availabe for public view
 |  | from | 198 |  |  |
| | | from | 198 | | |
Abstract
Therapeutic targeting of the JAK/STAT pathway, the principal signaling mechanism for numerous cytokines, might be an effective approach for limiting inflammation in different organs, including the liver. Therefore, we investigated whether targeting this pathway by the novel JAK inhibitor ruxolitinib could mitigate hepatic damage in mice and, if so, what would be the potential mechanisms. Using two different models. 1- (Carbon tetrachloride) CCl4 induced acute liver injury. 2- (Thioacetamide) TAA induced acute liver injury. Various doses of ruxolitinib (75 and 150 mg/kg in CCl4 model and 50,100 and 200 mg/kg in TAA model) were orally administered to overnight fasted mice 2 hr prior to intraperitoneal (i.p.) intoxication with CCl4 (0.03 ml/Kg in olive oil) or TAA (300 mg/kg in physiological saline). After 24 h and 30 h from CCl4 and TAA challenge respectively, mice were anaesthetized with thiopental and sample were collected for investigation of markers for hepatic injury, necrosis, apoptosis, inflammatory cytokines and oxidative stress, as well as promotion of hepatic regeneration. In conclusion, the multimechanistic hepatoprotective activity of ruxolitinib can be linked to its ameliorative properties on cellular death, oxidative stress and inflammation machinery as well as promoting hepatocyte regeneration.