Regulatory Effects of Fenofibrate with Inflammatory Response and Myocardiac Dysfunction in Lipopolysaccharide-stimulated Heart Tissues

ABSTRACT

PURPOSE: This study was intended to establish experimental conditions for monitoring the cardioprotective effects of fenofibrate on cardiac function in lipopolysaccharide (LPS)-stimulated BalB/c mice. METHODS: To investigate the effects of fenofibrate on cardiac function, expression of Peroxisome proliferator-activated receptors (PPARs) and Peroxisome proliferator-activated receptor Gamma coactivator 1(PGC-1) and its target gene in the heart tissues of mice was compared after controls and LPS injection with pretreated fenofibrate or alone using reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemistry. In addition, Enzyme-linked-immunosorbent-assays (ELISA) were performed for assessment of pro-inflammatory cytokines of blood serum. RESULTS: Pretreated with fenofibrate had protective effects of diminishing the levels of LPS-induced pro-inflammatory cytokines, including interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) and recovery from reduction of messenger Ribo-nucleic acid, protein level of PPARs and PGC-1 in LPS-administered heart tissue. In addition, increasing expression of PPARs and PGC-1 ameliorated the expression and activity of catalase blocked production of lipid peroxidation. CONCLUSION: Treatment with fenofibrate resulted in augmented expression of transcription factors and reduced production of pro-inflammatory cytokines and lipid peroxidation after LPS administration. Therefore, results of this study suggested that fenofibrate should not only have a protective effect but should also restore cardiac function in several cardiac dysfunctional situations.