Osthole prevents intestinal ischemia-reperfusion-induced lung injury in a rodent model

J Surg Res. 2014 Jun 15;189(2):285-94. doi: 10.1016/j.jss.2014.03.026. Epub 2014 Mar 15.

Abstract

Background: Intestinal ischemia-reperfusion (II/R) is associated with high morbidity and mortality. The aim of this study was to investigate the effects of osthole on lung injury and mortality induced by II/R.

Methods: A rat model of II/R was induced by clamping the superior mesenteric artery for 90 min followed by reperfusion for 240 min. Osthole was administrated intraperitoneally at 30 min before intestinal ischemia (10 or 50 mg/kg). The survival rate and mean arterial pressure were observed. Blood samples were obtained for blood gas analyses. Lung injury was assessed by the histopathologic changes (hematoxylin and eosin staining), lung wet-to-dry weight ratio, and pulmonary permeability index. The levels of reactive oxygen species, malondialdehyde, interleukin 6, and tumor necrosis factor α, as well as the activities of superoxide dismutase and myeloperoxidase in lung were measured.

Results: The survival rate, ratio of arterial oxygen tension to fraction of inspired oxygen, and mean arterial pressure decreased significantly after II/R. Results also indicated that II/R-induced severe lung injury evidenced by increase in pathologic scores, lung wet-to-dry weight ratio, and pulmonary permeability index, which was accompanied by increases in the levels of pulmonary reactive oxygen species, malondialdehyde, interleukin 6, tumor necrosis factor α, and the pulmonary myeloperoxidase activity and a decrease in superoxide dismutase activity. Osthole could significantly ameliorate lung injury and improve the previously mentioned variables.

Conclusions: These findings indicated that osthole could attenuate the lung injury induced by II/R in rats, at least in part, by inhibiting inflammatory response and oxidative stress.

Keywords: Inflammatory response; Intestinal ischemia–reperfusion; Lung injury; Osthole; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / etiology
  • Acute Lung Injury / pathology
  • Acute Lung Injury / prevention & control*
  • Animals
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use*
  • Coumarins / pharmacology
  • Coumarins / therapeutic use*
  • Disease Models, Animal
  • Interleukin-6 / metabolism
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Malondialdehyde / metabolism
  • Organ Size / drug effects
  • Oxidative Stress / drug effects
  • Peroxidase / metabolism
  • Pulmonary Gas Exchange / drug effects
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / etiology
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Calcium Channel Blockers
  • Coumarins
  • Interleukin-6
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Peroxidase
  • Superoxide Dismutase
  • osthol