الفهرس 
Introductionيوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
The present study was conducted to investigate the protective effects of different inflammatory modulators, through different mechanisms. A serine protease; alpha-chymotrypsin, chimeric monoclonal antibody to tumor necrosis factor-α; infliximab and a COX-2 inhibitor; celecoxib were tested for their protective effect in diminishing lung, liver and kidney injury induced by sepsis. In addition, the study aimed to further investigate the anti-inflammatory and anti-oxidant effects and compare the effect of these treatments.
Two separate designs were involved in this study: mechanistic and survival studies. Induction of sepsis was via CLP. Wister rats were randomized into six groups: sham group, CLP-operated group, CLP-treated by alpha-chymotrypsin, celecoxib and infliximab after 2 hours from surgery. Sham rats were subjected to the same procedure except the ligation and puncture of cecum. Following the induction by 24 hours, all rats were sacrificed. Blood and tissue samples were collected. The same set of groups were applied in a separate number of rats for the survival study.
To investigate the effects of these treatments the following procedures were performed:
• Biochemical analyses involving measurement of liver enzymes; ALT, AST for assessment of liver function, creatinine, BUN, and Cystatin-C for kidney function, wet/dry ratio of lobe of the lung, leucocytic count and protein concentration in bronchoalveolar lavage of the lung.
• Antioxidant activity; reduced glutathione and superoxide dismutase activity and oxidative stress; malondialdehyde and total nitrite concentrations and in the lung, liver and kidney tissues.
• Serum levels of TNF-α, IL-1and IL-6.
• Histopathological examination of lung, liver and kidney tissues from each group.
The results of this study can be summarized by:
1- The induction of sepsis following application of the CLP model resulted in deleterious effects on lung, liver and kidney in both structure and function.
2- CLP-operated rats were associated with high mortality at the first day of observation and by the second day there were no survived rats. The histopathological changes were observed in septic rats and were compared to sham-operated rats. Such changes were correlated with increased lung, liver and kidney injury markers, oxidative stress as shown by reduced activity of SOD with low level of GSH and increased levels of MDA and NOx. Moreover, serum levels of the pro-inflammatory cytokines: TNF-α IL-1and IL-6 were raised.
3- Treatment with alpha-chymotrypsin (40 U/kg, i.m), celecoxib (0.1 mg/kg, p.o) and infliximab (5mg/kg, s.c) diminished the biochemical changes in septic lung, liver and kidney tissues. In addition to the improvement in survival with restoration of normal architecture and normal functions of the lung, liver and kidney. Furthermore, the inhibition of sepsis -induced elevation in cellular oxidative stress which was demonstrated as lowering of MDA and NOx and elevation of the activity of SOD and GSH level. Also, the levels of inflammatory cytokines TNF-α IL-1and IL-6 were reduced.
In conclusion, our study provides an evidence of the protective effect of alpha-chymotrypsin, celecoxib and infliximab against sepsis induced acute lung, kidney and liver injury. These effects are attributed to anti-inflammatory and antioxidant effects of of alpha-chymotrypsin, celecoxib and infliximab. Clinical studies are recommended to confirm the beneficial effects of these
drugs in human during sepsis that may offer a promising strategy for sepsis patients.