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

Title
Renoprotective Effects of Carbon Monoxide-Releasing Molecule 3 in Ischemia-Reperfusion Injury and Cisplatin-Induced Toxicity.
Author
윤영은
Keywords
INDUCED APOPTOSIS; CELL-DEATH
Issue Date
2017-06
Publisher
ELSEVIER SCIENCE INC
Citation
TRANSPLANTATION PROCEEDINGS, v. 49, no. 5, page. 1175-1182
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 mu M) were assessed in normal kidney epithelial cells (HK-2, LLC-PK1) and renal cancer cells (Caki-1, Caki-2) subjected to cisplatin (50-200 mu M) or IRI. To induce IRI, cells were placed in an anaerobic chamber (37 degrees C, 95% nitrogen, 5% carbon dioxide) for 48 hours. Cells were transferred to complete medium and incubated at 37 degrees C, 5% carbon dioxide for 6 hours. Cell viability (CCK assays), tumor necrosis factor (TNF)-alpha 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-mu M 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-alpha, mRNA was induced by stimulated IRI or cisplatin exposure; CORM-3 pretreatment attenuated the rise in TNF-alpha 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.
URI
https://www.sciencedirect.com/science/article/abs/pii/S0041134517302877?via%3Dihubhttps://repository.hanyang.ac.kr/handle/20.500.11754/114523
ISSN
0041-1345; 1873-2623
DOI
10.1016/j.transproceed.2017.03.067
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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