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J Korean Soc Emerg Med > Volume 23(5); 2012 > Article
Journal of The Korean Society of Emergency Medicine 2012;23(5): 721-729.
Regulatory Effects of Fenofibrate with Inflammatory Response and Myocardiac Dysfunction in Lipopolysaccharide-stimulated Heart Tissues
Dong Hoon Song, Yong Hwang, Su Jin Yoo
Department of Emergency Medicine, Wonkwang University College of Medicine, Iksan, Korea. ysoojin@wmc.wonkwang.ac.kr
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.
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.
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.
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.
Key words: Sepsis, Lipopolysaccharide, Cardiac dysfunction, Fenofibrate
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