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Current Therapeutic Research, Clinical and Experimental logoLink to Current Therapeutic Research, Clinical and Experimental
. 2004 May;65(3):278–291. doi: 10.1016/S0011-393X(04)80087-0

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

Eray Kara 1,*, Ahmet Var 2, Seda Vatansever 3, Serap Cilaker 3, Yavuz Kaya 1, Teoman Coşkun 1
PMCID: PMC3964556  PMID: 24672083

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.

Full Text

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