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 mM) were assessed in normal kidney epithelial cells (HK-2, LLC-PK1) and renal cancer cells (Caki-1, Caki-2) subjected to cisplatin (50–200 mM) or IRI. To induce IRI, cells were placed in an anaerobic chamber (37[deg]C, 95% nitrogen, 5% carbon dioxide) for 48 h. Cells were transferred to complete medium and incubated at 37[deg]C, 5% carbon dioxide for 6 h. Cell viability (CCK assays), TNF-a mRNA levels (quantitative reverse-transcriptase PCR), and protein expression of C-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-mM CORM-3-pretreated cells compared with control. The protective effects of CORM-3 in cells exposed to cisplatin for 24 h were weaker than in the IRI model. TNF-a mRNA was induced by stimulated IRI or cisplatin exposure; CORM-3 pretreatment attenuated the rise in TNF-a mRNA. IRI or cisplatin-induced activated oxidative stress markers decreased in CORM-3 pretreated cells. CORM-3 reduced expression of the apoptotic marker C-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.

CITATION INFORMATION: Yoon Y, Lee H, Huh K, Kim M, Kim S, Kim Y, Han W. Renoprotective Effects of Carbon Monoxide–Releasing Molecule 3 in Ischemia Reperfusion Injury and Cisplatin-Induced Toxicity. Am J Transplant. 2017;17 (suppl 3).

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