Effects of Rofecoxib, a Selective Cyclooxygenase-2 Inhibitor, on Endothelial Dysfunction, Lipid Peroxidation, and Hepatocyte Morphology in Rats with Sepsis-induced Liver Damage

Overview

Journal Curr Ther Res Clin Exp

Specialty Pharmacology

Date 2014 Mar 28

PMID 24672083

Authors

Eray Kara

Ahmet Var

Seda Vatansever

Serap Cilaker

Yavuz Kaya

Teoman Coskun

Affiliations

Soon will be listed here.

Abstract

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 1 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.

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