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논문분류	춘계학술대회 초록집
제목	Pharmacologic inhibition of NADPH Oxidase4/Nox4 provides renoprotection in contrast induced nephropathy
저자	Se-Hee Yoon*, Bo-Young Jeong1, Hoi Young Lee1, Doo-ri Choi2, Seung-Yun Han2, Moon Hyang Park3, Kyung-Ho Lee4, Dong-Il Kim4, Won-Min Hwang4, Sung-Ro Yun4
출판정보	2016; 2016(1):
키워드	contrast induced nephropathy , Nox4, reactive oxygen species
초록	Background: Contrast induced nephropathy may occur, in part, as a result of intrarenal oxidative stress. NADPH oxidases are important sources of reactive oxygen species (ROS). Among various type of NADPH oxidases, Nox4 is expressed predominantly in rodent kidney. The aim of the present study was to assess the effect of Nox4 inhibition on the prevention of contrast induced nephropathy (CIN). Methods: Using HK-2 cells, Nox4 mRNA and protein were determined after exposure to iohexol with/without pretreatment of the most specific Nox1/4 inhibitor, GKT137831. Caspase3/7 activity, DHE stain and amplex red activity were also measured. Proinflammatory and apoptotic markers (pNFkB/NFkB, pp38/p38, pJNK/JNK, pERK/ERK and pcleaved caspase/caspase) were measured for investigation of intracellular pathway associated with Nox4. In addition, the effect of Nox4 inhibition were evaluated in mice model of CIN. Results: The expression of Nox4 in HK-2 cells significantly increased by iohexol exposure. Pretreatment of GKT137831 resulted in reduced production of ROS, down regulation of proinflammatory marker (p38), that are implicated in CIN, reduced caspase 3/7 activity and increased cellular survival in iohexol exposed HK-2 cells. Silencing of the Nox4 gene replicated theses effects by down regulation of proinflammatory markers. In CIN mice model, pretreatment with GKT137831 resulted in an attenuated vacuolar degeneration, tubular epithelial cell shedding, cellular cast formation and tubular dilatation. Conclusion: Collectively, these results identify Nox4 as a key source of ROS responsible for kidney injury in CIN and provide proof of principle for an innovative small molecule approach to prevent contrast induced nephropathy. Table:
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