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Öğe Celecoxib administration reduced mortality, mesenteric hypoperfusion, aortic dysfunction and multiple organ injury in septic rats(ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2017) Ozer, Erdem Kamil; Goktas, Mustafa Tugrul; Kilinc, Ibrahim; Bariskaner, Hulagu; Ugurluoglu, Ceyhan; Iskit, Alper BektasBackground: 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. 2 h after Sham and CLP operations, celecoxib (0.5 mg/kg) or vehicle (saline; 1 mL/kg) was administered orally to rats. 18 h 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 96 h. 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 96 h. 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. (C) 2016 Elsevier Masson SAS. All rights reserved.Öğe Coenzyme Q10 improves the survival, mesenteric perfusion, organs and vessel functions in septic rats(ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2017) Ozer, Erdem Kamil; Goktas, Mustafa Tugrul; Kilinc, Ibrahim; Pehlivan, Sultan; Bariskaner, Hulagu; Ugurluoglu, Ceyhan; Iskit, Alper BektasBackground: Coenzyme Q10 (CoQ10) is a naturally occurring, lipid-soluble antioxidant and an essential electron carrier in the mitochondrial respiratory chain. In sepsis, CoQ10 deficiency induced by mitochondrial failure can lead to hypoxia, hypoperfusion, oxidative organ damage and finally death. We aimed to investigate the effects of CoQ10 on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis. Methods: Wistar rats were divided into Sham, CLP, Sham + CoQ10, CLP + CoQ10 subgroups. CoQ10 (10 mg/kg/day) or vehicle (olive oil; 1 mL/kg/day) was intraperitoneally injected for 15 days. At 16th day, Sham or CLP operation was performed. 20 h after the operations, MABF and phenylephrine responses of isolated aortic rings were measured. Tissue samples were obtained for histopathological and biochemical evaluations. Furthermore, survival rates were monitored throughout 96 h. Results: CoQ10 prevented mesenteric hypoperfusion and aortic dysfunction induced by CLP. Survival rate was % 0 at 46th h in CLP group, but in CLP + CoQ10 group it was 37.5% at the end of 96 h. CLP-induced elevations of serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were blocked by CoQ10. CoQ10 restored the increased liver, lung, spleen and kidney malondialdehyde levels and as well as reduced liver and spleen glutathione levels. The protective effects of CoQ10 on multiple organ damage were also observed histopathologically. Conclusions: CoQ10 showed protective effects in sepsis due to its preservative effects on mesenteric perfusion, aortic function and also its anti-inflammatory and antioxidative effects. (C) 2017 Elsevier Masson SAS. All rights reserved.Öğe The effect of morphine delta receptor activity on ischemic postconditioning in lung ischemia reperfusion injury(TURKISH RESPIRATORY SOC, 2018) Duzgun, Nuri; Esme, Hidir; Kilinc, Ibrahim; Calik, MustafaOBJECTIVE: In the context of the physiopathology of lung damage due to ischemia and reperfusion injury, we aimed to reveal the effects of the addition of morphine sulfate to ischemic postconditioning (PC) protocol. METHODS: In the present study, 48 Wistar albino female rats were employed. Group 1 was accepted as the Sham group that underwent thoracotomy through the fifth left intercostal space. Ischemia-reperfusion (IR) group: Thoracotomy and IR period. IRPC group: thoracotomy, IR period and ischemic PC. In IRPC3 and IRPC30 groups, in addition to ischemic PC different doses of morphine sulfate (3 mu mol and 30 mu mol) was administered. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-10 levels were measured in the biochemical assessment of the lung tissue samples obtained. RESULTS: TNF-alpha and IL-1 (pro-inflammatory cytokines) have lower values, and IL-10 (anti-inflammatory cytokine) have higher values both in the groups which have been subject to PC and morphine. TNF-alpha and IL-1 levels in lung tissue were statistically significant between the IRPC3 group and the IR and IRPC groups. In addition, IL-10 level in lung tissue was statistically significant between the IRPC3 group and the IRPC group. CONCLUSION: In the present study conducted with experimental animals where morphine was also injected beside ischemic PC protocols, statistically significant differences were determined in the lung tissue analyses when we compared pro-inflammatory and anti-inflammatory cytokine values. We firmly believe that adding morphine to the lung transplantation protocols and PC will decrease IR damage.Öğe Infliximab alleviates the mortality, mesenteric hypoperfusion, aortic dysfunction, and multiple organ damage in septic rats(CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS, 2017) Ozer, Erdem Kamil; Goktas, Mustafa Tugrul; Kilinc, Ibrahim; Toker, Aysun; Bariskaner, Hulagu; Ugurluoglu, Ceyhan; Iskit, Alper BektasTumor necrosis factor-alpha (TNF-alpha) is a pivotal mediator that triggers inflammatory process, oxidative stress, and multiple organ injury in sepsis. We investigated the effects of infliximab on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis. Wistar rats were divided into Sham, CLP, Sham+infliximab, and CLP+infliximab subgroups. Twenty-four hours before the operations, rats were injected intraperitoneally with infliximab (7 mg/kg) or vehicle (saline; 1 mL/kg). Twenty hours after the operations, MBF and phenylephrine responses of isolated aortic rings were measured. Tissue damages were examined biochemically and histopathologically. Furthermore, survival rates were monitored throughout 96 h. Infliximab improved survival, mesenteric perfusion, and aortic function after CLP. Increases of serum AST, ALT, LDH, BUN, Cr, and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) induced by CLP were blocked by infliximab. Infliximab prevented malondialdehyde elevations in septic liver, lung, spleen, and kidney tissues, as well as glutathione reductions in septic liver, spleen, and kidney tissues. Protective effects of infliximab on multiple organ damage were also observed histopathologically. Infliximab showed protective effects in sepsis due to its improvement effects on mesenteric perfusion, aortic function, and its anti-inflammatory and antioxidative effects.
