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 language | English |
|---|---|
| Pages (from-to) | 1175-1182 |
| Number of pages | 8 |
| Journal | Transplantation Proceedings |
| Volume | 49 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2017 Jun |
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All Science Journal Classification (ASJC) codes
- Surgery
- Transplantation
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Renoprotective Effects of Carbon Monoxide–Releasing Molecule 3 in Ischemia-Reperfusion Injury and Cisplatin-Induced Toxicity. / Yoon, Y. E.; Lee, K. S.; Lee, Y. J.; Lee, H. H.; Han, W. K.
In: Transplantation Proceedings, Vol. 49, No. 5, 06.2017, p. 1175-1182.Research output: Contribution to journal › Article
TY - JOUR
T1 - Renoprotective Effects of Carbon Monoxide–Releasing Molecule 3 in Ischemia-Reperfusion Injury and Cisplatin-Induced Toxicity
AU - Yoon, Y. E.
AU - Lee, K. S.
AU - Lee, Y. J.
AU - Lee, H. H.
AU - Han, W. K.
PY - 2017/6
Y1 - 2017/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85020219403&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020219403&partnerID=8YFLogxK
U2 - 10.1016/j.transproceed.2017.03.067
DO - 10.1016/j.transproceed.2017.03.067
M3 - Article
C2 - 28583551
AN - SCOPUS:85020219403
VL - 49
SP - 1175
EP - 1182
JO - Transplantation Proceedings
JF - Transplantation Proceedings
SN - 0041-1345
IS - 5
ER -