کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5849233 | 1561748 | 2016 | 12 صفحه PDF | دانلود رایگان |
- Ruxolitinib effect was investigated on thioacetamide (TAA)-induced hepatotoxicity.
- Ruxolitinib combated TAA-induced hepatic injury and necroinflammation.
- Ruxolitinib reduced TAA-induced hepatic apoptosis and inflammatory cells infiltration.
- Ruxolitinib counteracted TAA-induced hepatic oxidative stress.
- Ruxolitinib dampened TAA-induced overproduction of proinflammatory cytokines.
In an attempt to explore the role of the JAK/STAT pathway in liver inflammation, we investigated the effect of intervening this pathway by ruxolitinib in thioacetamide (TAA)-induced hepatotoxicity. Ruxolitinib treatments were administered to male mice either before or after intoxication with TAA. The hepatic histopathological and serum biochemical assessment revealed that ruxolitinib pre-treatments dose-dependently reduced TAA-induced liver injury, caspase 3 cleavage and increase in number of hepatocytes positive for the pro-apoptotic Bax, as well as inflammatory cells positive for F4/80 and myeloperoxidase activity in the liver. Ruxolitinib pre-treatments also curbed TAA-induced rise in NF-κB nuclear expression and STAT3 phosphorylation. Ruxolitinib pre-treatments also lowered TAA-induced elevation of hepatic oxidative stress parameters (total nitrate/nitrite and 4-hydroxynonenal), but did not restore the hepatic antioxidant reduced glutathione. Interestingly, ruxolitinib, especially at a dose of 200 mg/kg, dampened the overproduction of pro-inflammatory cytokines (TNF-α, IL-1β, IFN-γ, IL-23 and IL-17A), which coincided with boosting the release of the anti-inflammatory cytokine IL-10. Ruxolitinib when used as a post-treatment (1 and 3 h after TAA-insult) could still spare the liver from injury and might be clinically applicable. In conclusion, the multimechanistic-hepatoprotective activity of ruxolitinib can be linked to its ameliorative properties on cellular death, oxidative stress and inflammation machinery.
Journal: Food and Chemical Toxicology - Volume 96, October 2016, Pages 290-301