Effects of the COX-2 inhibitor FK3311 on ischemia - reperfusion injury in the rat lung

J Invest Surg. 2007 May-Jun;20(3):175-80. doi: 10.1080/08941930701365986.

Abstract

Ischemia-reperfusion injury is induced by activation of the arachidonic acid cascade following the induction of cyclooxygenase-2. This study evaluated the effects of a selective cyclooxygenase-2 inhibitor, FK3311, on warm ischemia-reperfusion injury in the lung. Male Wistar rats were divided into two groups. In the FK3311 group (n = 27), FK3311 (4 mg/kg) was administered intravenously 5 min before ischemia, while in the control group (n = 27) only vehicle was injected. Warm ischemia was induced for 1 h by clamping the left hilus. The arterial oxygen pressure (PaO(2)) and saturation (SaO(2)) were measured 30 and 120 min after reperfusion. Serum thromboxane B(2) and 6-keto-prostaglandin F(1alpha) were also measured 30 min after reperfusion. Lung specimens were harvested 120 min after reperfusion for histologic examination and polymorphonuclear counts, and immunostained with cyclooxygenase-2. The 1-week survival rate in the two groups was compared. PaO(2) and SaO(2) 30 and 120 min after reperfusion were significantly (p < .05) better in the FK3311 group. Serum thromboxane B(2) levels were significantly (p < .05) lower in the FK3311 group. However, there was no significant difference in 6-keto-prostaglandin F(1alpha). Histologically, tissue damage was mild and polymorphonuclear infiltration was reduced in the FK3311 group compared to the control group. The expression of cyclooxygenase-2 in the alveolar epithelium based on immunostaining was suppressed in the FK3311 group. The 1-week survival rate was significantly (p < .05) higher in the FK3311 group. We conclude that FK3311 has protective effects on pulmonary ischemia-reperfusion injury, and results in improvement in the 1-week survival rate.

MeSH terms

  • Anilides / pharmacology*
  • Animals
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase Inhibitors / pharmacology*
  • Lung Diseases / drug therapy*
  • Lung Diseases / immunology
  • Lung Diseases / pathology
  • Male
  • Neutrophils / pathology
  • Oxygen / blood
  • Pulmonary Alveoli / enzymology
  • Pulmonary Alveoli / immunology
  • Pulmonary Alveoli / pathology
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / immunology
  • Reperfusion Injury / pathology
  • Survival Rate
  • Thromboxane B2 / blood

Substances

  • Anilides
  • Cyclooxygenase Inhibitors
  • FK 3311
  • Thromboxane B2
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Oxygen