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Renoprotective Effects of Carbon Monoxide-Releasing Molecule 3 in Ischemia-Reperfusion Injury and Cisplatin-Induced Toxicity.

Authors
 Y.E. Yoon  ;  K.S. Lee  ;  Y.J. Lee  ;  H.H. Lee  ;  W.K. Han 
Citation
 TRANSPLANTATION PROCEEDINGS, Vol.49(5) : 1175-1182, 2017 
Journal Title
 TRANSPLANTATION PROCEEDINGS 
ISSN
 0041-1345 
Issue Date
2017
MeSH
Animals ; Cell Line ; Cell Survival/drug effects ; Cisplatin/toxicity* ; Epithelial Cells/drug effects* ; Humans ; Kidney/drug effects* ; Organometallic Compounds/pharmacology* ; Reperfusion Injury/metabolism* ; Tumor Necrosis Factor-alpha/metabolism
Abstract
BACKGROUND: We investigated the effects of a soluble carbon monoxide-releasing molecule (CORM) in cisplatin-induced cytotoxicity and ischemia-reperfusion injury (IRI) in vitro. METHODS: The effects of CORM-3 (12.5-200 μM) were assessed in normal kidney epithelial cells (HK-2, LLC-PK1) and renal cancer cells (Caki-1, Caki-2) subjected to cisplatin (50-200 μM) or IRI. To induce IRI, cells were placed in an anaerobic chamber (37°C, 95% nitrogen, 5% carbon dioxide) for 48 hours. Cells were transferred to complete medium and incubated at 37°C, 5% carbon dioxide for 6 hours. Cell viability (CCK assays), tumor necrosis factor (TNF)-α messenger RNA (mRNA) levels (quantitative reverse-transcriptase polymerase chain reaction), and protein expression of cleaved-caspase 3 and oxidative stress markers (including Erk1/2, JNK, and P38; Western blot) were assessed. RESULTS: Viability after IRI was approximately 40% of control. Protective effects of CORM-3 in the IRI model were dose-dependent. Cell viability was 40% recovered in 200-μM CORM-3-pretreated cells compared with control. The protective effects of CORM-3 in cells exposed to cisplatin for 24 hours were weaker than in the IRI model. TNF-α mRNA was induced by stimulated IRI or cisplatin exposure; CORM-3 pretreatment attenuated the rise in TNF-α mRNA. IRI or cisplatin-induced activated oxidative stress markers decreased in CORM-3-pretreated cells. CORM-3 reduced expression of the apoptotic marker cleaved-caspase 3. CONCLUSION: Our data demonstrate the protective effects of CORM-3 in cisplatin cytotoxicity and IRI in both normal kidney cells and renal cancer cells in vitro. CORM-3 exerts these effects by ameliorating inflammatory and oxidative stress pathways.
Full Text
https://www.sciencedirect.com/science/article/pii/S0041134517302877
DOI
10.1016/j.transproceed.2017.03.067
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Young Eun(윤영은)
Lee, Kwang Suk(이광석) ORCID logo https://orcid.org/0000-0002-7961-8393
Lee, Hyung Ho(이형호)
Han, Woong Kyu(한웅규) ORCID logo https://orcid.org/0000-0002-2527-4046
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160342
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