title: Celecoxib administration reduced mortality, mesenteric hypoperfusion, aortic dysfunction and multiple organ injury in septic rats.
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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Selcuk University, Konya, Turkey. Electronic address: drekfarma@hotmail.com.
authors.forename: Erdem Kamil
authors.initials: EK
authors.lastname: Ozer
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Yildirim Beyazit University, Ankara, Turkey.
authors.forename: Mustafa Tugrul
authors.initials: MT
authors.lastname: Goktas
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Kilinc
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Selcuk University, Konya, Turkey.
authors.forename: Hulagu
authors.initials: H
authors.lastname: Bariskaner
authors.affiliation: Department of Pathology, Faculty of Medicine, Selcuk University, Konya, Turkey.
authors.forename: Ceyhan
authors.initials: C
authors.lastname: Ugurluoglu
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors.forename: Alper Bektas
authors.initials: AB
authors.lastname: Iskit
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001018:Aortic Diseases / Q000188:drug therapy* / Q000378:metabolism; D000068579:Celecoxib / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D065666:Mesenteric Ischemia / Q000188:drug therapy* / Q000378:metabolism; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D015996:Survival Rate
chemical_list: D016207:Cytokines; D008315:Malondialdehyde; D005978:Glutathione; D000068579:Celecoxib
keywords: Celecoxib; Mesenteric arterial blood flow; Sepsis; Survival and multiple organ damage; Vascular hyporeactivity