Protective effects of fenofibrate against acute lung injury induced by intestinal ischemia/reperfusion in mice

Zhu, Qiankun; He, Guizhen; Wang, Jie; Wang, Yukang; Chen, Wei

In the present study, we demonstrated that the intestinal I/R negatively affected lung morphology and induced acute lung injury, characterized by systemic inflammation and apoptotic cell death in the lung epithelium. Mice treated with fenofibrate showed an ameliorated inflammatory responses and decreased apoptotic indicators in both the intestine and the distant organ, including the lung, after intestinal I/R. Moreover, fenofibrate improved the survival rate in the model of intestinal I/R. To the best of our knowledge, this is the first study showing a protective effect of fenofibrate on intestinal I/R-induced ALI, albeit the protective effectiveness has been proved on alleviating the injury in other organs that had undergone I/R [10] [11] [12] 15 . In a rat model of 60-min renal ischemia followed by 24 hours of reperfusion, administration of fenofibrate alleviated the MDA content, the MPO activity, and the generation of proinflammatory mediators. In addition, the expression of nitric oxide (NO), a marker of oxidative damage, was reduced by the treatment of fenofibrate in the renal I/R model 10 . In the cardiac I/R model, fenofibrate effectively attenuated the cardiac injury by reduction of the infarct size and oxidative stress 15 . Our apriori hypothesis was partly based on the anti-oxidant and anti-inflammation properties of fenofibrate. One experiment 20 with fenofibrate intervention in rheumatoid arthritis patients indicated that a three month long administration of fenofibrate (145 mg/kg) alleviated the inflammatory mediators, C reactive protein and IL-6, in the circulation. Jia, Z et al 21 . found out that fenofibrate decreased the level of HMGB1, a downstream protein of TLR4, and therefore attenuated the inflammation in the cardiac cells. Their result on HMGB1 is consistent with one of our experiment results in which the HMGB1 of the small intestine was significantly down-regulated after fenofibrate treatment.