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

Y. E. Yoon, K. S. Lee, Y. J. Lee, H. H. Lee, W. K. Han

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1175-1182
Number of pages8
JournalTransplantation Proceedings
Volume49
Issue number5
DOIs
Publication statusPublished - 2017 Jun

All Science Journal Classification (ASJC) codes

  • Surgery
  • Transplantation

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