الفهرس 
Introduction & Aim of the workOnly 14 pages are availabe for public view
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Abstract
Sepsis is considered one of the most serious medical conditions that leads to death by causing multiple organ failure specially liver and kidney. Different pathological mechanisms are included in sepsis. In a trial for examining the role of XO enzyme in sepsis, FEB was tested which is XO inhibitor, in a model of CLP. The study explored the possible protective effect of FEB in sepsis induced hepatotoxicity and nephrotoxicity. Therapeutic approaches targeting this pathway represent a promising opportunity in the present study.
Through this study, 48 rats were divided into 4 groups: sham group was supplemented with vehicle (carboxy methyl cellulose) and undergone the laparotomy without CLP, sham pretreated with FEB group was supplemented with FEB (10 mg/kg PO once daily for 2 days and 30 min prior to laparotomy without CLP), CLP group was supplemented with vehicle (carboxy methyl cellulose) and undergone the laparotomy with CLP, CLP pretreated with FEB group was supplemented with FEB (10 mg/kg PO once daily for 2 days and 30 min prior to laparotomy with CLP). After 24 h from CLP, half of these animals in each group were sacrificed then liver and kidney were excised. The other half of these animals in each group were under observation to detect the survival rate.
Liver and kidney injuries were evaluated biochemically including AST, ALT, urea, creatinine, NGAL, uric acid. Antioxidant and oxidant indicators; TAO, SOD, MDA, NO were also measured. Antiinflammatory indicators including TNF α, IL 1β, JNK and NF-κb and appoptotic factor caspase 3 were evaluated. Also the injuries were evaluated histologically.
Data of the present study showed that CLP group increased the level of AST, ALT, creatinine, NGAL, uric acid, MDA, NO however it decreased the level of TAO, SOD. Also, it increased the expression of NF-κb, IL 1β, JNK and caspase 3 with high mortality rate. Histopathological examination in liver showed severe hepatocellular injury with marked loss of architecture, severe periportal inflammation, sinusoidal congestion and necroinflammatory foci of hepatocytes and in kidney showed markedly impaired renal morphology with severe Bowman’s capsule degeneration, proximal and distal tubules degeneration and interstitial edema.
Pretreatment with FEB showed significant improvement in all measured parameters. Also it could ameliorate the degenerative histopathological changes and improve the survival rate.
Taken together, the current study concludes that pretreatment with FEB could attenuate CLP induced hepatotoxicity and nephrotoxicity. The protective effect of FEB may be explained by the inhibition of XO, antioxidant, anti-inflammatory and anti-apoptotic effects of FEB with involvement of different pathways including NF-κB and JNK pathway. These findings may offer an encouraged way for therapeutic application of FEB in sepsis-induced liver and kidney injuries.