The proinflammatory cytokine-mediated protective effects of pentoxifylline, iloprost, and cilostazol on a mitigating lung injury induced by lower limb ischemia and reperfusion in rats

Abstract

Background: This study aims to elucidate whether pentoxifylline, iloprost and cilostazol mitigates acute lung injury induced by lower limb ischemia-reperfusion (I/R) and their protective effects cover cytokines. Methods: Forty rats were randomized into five groups: control (group 1), ischemia-reperfusion (group 2), pentoxifylline (group 3), iloprost (group 4), iloprost and cilostazol (group 5). All drugs were administered before ischemia. Samples were obtained for tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and total sialic acid (TSA) assays. Findings of lung injury were examined. Results: Interleukin-6 and TNF levels were increased at 90 minutes and sustained elevated even after 240 minutes. In groups 3 and 4, IL-6 and TNF levels were significantly lower at 90, 180 and 240 minutes compared to group 2. At 180 minutes, TSA levels in groups 2, 3, 4 and 5 were significantly different from baseline and 90 minute levels. At this time point, TSA levels of group 2 and 3 were significantly higher compared to group 4 and 5. Conclusion: In this acute lung injury model induced by I/R of the lower limbs, pretreatment with pentoxifylline, iloprost and cilostazol significantly attenuated proinflammatory activities and parenchymal lung damage.