Celecoxib administration reduced mortality, mesenteric hypoperfusion, aortic dysfunction and multiple organ injury in septic rats - 17/01/17
, Mustafa Tugrul Goktas b, Ibrahim Kilinc c, Hulagu Bariskaner a, Ceyhan Ugurluoglu d, Alper Bektas Iskit eBienvenue sur EM-consulte, la référence des professionnels de santé.
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| pages | 7 |
| Iconographies | 4 |
| Vidéos | 0 |
| Autres | 0 |
Highlights |
• | Cyclooxygenase (COX)-2 overexpression plays a principal role in sepsis related multiple organ dysfunction and death. |
• | Selective and partial COX-2 inhibition by celecoxib without affecting the physiological basal COX-2 activity has benefical effects in sepsis. |
• | Celecoxib reduced mortality, vascular dysfunction, mesenteric hypoperfusion and organ damage in cecal ligation and pucture induced septic rats. |
• | Selective and partial blockade of COX-2 is a therapeutic target in sepsis therapy |
Abstract |
Background |
The cyclooxygenase (COX)-2 overexpression is associated with vascular injury and multiple organ failure in sepsis. However, constitutive COX-1 and basal COX-2 expressions have physiological effects. We aimed to investigate the effects of partial and selective COX-2 inhibition without affecting constitutive COX-1 and basal COX-2 activities by celecoxib on mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries, and survival in septic rats accomplished by cecal ligation and puncture (CLP).
Methods |
Wistar rats were allocated into Sham, CLP, Sham+celecoxib, CLP+celecoxib subgroups. 2h after Sham and CLP operations, celecoxib (0.5mg/kg) or vehicle (saline; 1mL/kg) was administered orally to rats. 18h after drug administrations, MABF and responses of isolated aortic rings to phenylephrine were measured. Tissue samples were obtained for biochemical and histopathological examinations. Furthermore, survival rate was monitored throughout 96h.
Results |
Celecoxib ameliorated mesenteric hypoperfusion and partially improved aortic dysfunction induced by CLP. Survival rate was%0 at 49th h in CLP group, but in CLP+celecoxib group it was 42.8% at the end of 96h. Serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were increased in CLP group that were prevented by celecoxib. The decreases in liver and spleen glutathione levels and the increases in liver, lung, spleen and kidney malondialdehyde levels in CLP group were blocked by celecoxib. The histopathological protective effects of celecoxib on organ injury due to CLP were also observed.
Conclusions |
Celecoxib has protective effects on sepsis due to its preservative effects on mesenteric perfusion, aortic function and its anti-inflammatory and antioxidative effects.
Le texte complet de cet article est disponible en PDF.Keywords : Celecoxib, Sepsis, Survival and multiple organ damage, Vascular hyporeactivity, Mesenteric arterial blood flow
Plan
Vol 86
P. 583-589 - février 2017 Retour au numéro
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