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

• Published in: Transplantation proceedings Vol. 49; no. 5; pp. 1175 - 1182
• Main Authors: Yoon, Y.E, Lee, K.S, Lee, Y.J, Lee, H.H, Han, W.K
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-06-2017
• Subjects: Animals; Cell Line; Cell Survival - drug effects; Cisplatin - toxicity; Epithelial Cells - drug effects; Humans; Kidney - drug effects; Organometallic Compounds - pharmacology; Reperfusion Injury - metabolism; Surgery; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0041-1345; 1873-2623
• DOI: 10.1016/j.transproceed.2017.03.067

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.