Effects of rofecoxib, a selective cyclooxygenase-2 inhibitor, on endothelial dysfunction, lipid peroxidation, and hepatocyte morphology in rats with sepsis-induced liver damage

Background: Sepsis remains a difficult problem for clinicians, with its systemic effects and high morbidity and mortality rates. The roles of oxidative stress, endothelial dysfunction, and lipid peroxidation in sepsis-induced organ damage are being investigated. Objective: The aim of this study was to investigate the effects of selective cyclooxygenase (COX)-2 inhibition on tissue lipid peroxidation, endothelial dysfunction, and hepatic cell morphology in a rat model of sepsis. Methods: Thirty rats with sepsis induced by cecal ligation and puncture were divided equally into 3 groups: treatment group (rofecoxib 1 mg/kg PO), control group (saline 1 ml, PO), and sham group (sham surgery only). All the rats were sacrificed I day after sepsis induction. The livers were removed using a median laparotomy for histopathologic and biochemical analysis. Results: Histomorphologic hepatic damage and lipid peroxidation were significantly reduced in the rofecoxib treatment group compared with the control group (P < 0.05 and P = 0.001, respectively). Endothelial nitric oxide synthase and inducible nitric oxide synthase staining of liver samples was statistically significantly reduced in the treatment group compared with the control group (both, P < 0.001). The hepatic nitric oxide level and malonyldialdehyde activity decreased significantly (,P < 0.001 and P = 0.001, respectively) in the rofecoxib group compared with the control group. Hepatic myeloperoxidase activity was similar between the treatment and control groups. Conclusion: Further investigation of selective COX-2 inhibition as an alternate therapeutic choice for sepsis-induced hepatic damage should be considered.