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KMID : 1011820200610040441
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Investigative and Clinical Urology
2020 Volume.61 No. 4 p.441 ~ p.451
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Carbon monoxide?releasing molecule-3: Amelioration of renal ischemia reperfusion injury in a rat model
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Kim Dae-Keun
Shin Su-Jin
Lee Ji-Young
Park Sung-Yul
Kim Yong-Tae
Choi Hong-Yong
Yoon Young-Eun
Moon Hong-Sang
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Abstract
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Purpose: Despite the role of carbon monoxide in ameliorating ischemia-reperfusion injury (IRI), its use in the clinical setting is restricted owing to its toxicity. Herein, we investigated the in vivo effects of carbon monoxide?releasing molecule-3 (CORM-3) on IRI.
Materials and Methods: Fifteen rats were equally and randomly divided into three groups: sham (right nephrectomy), control (right nephrectomy and left renal ischemia), and CORM-3 (right nephrectomy and CORM-3 injection before left renal ischemia). Kidney tissues and blood samples collected from sacrificed rats were evaluated to determine the renoprotective effect and mechanism of CORM-3.
Results: Concentrations of serum creatinine and kidney injury molecule-1 in the CORM-3 group were significantly lower than in the control group after 75 minutes of IRI (1.2 vs. 2.4 mg/dL, p=0.01, and 292 vs. 550 pg/mL, p<0.001, respectively). Furthermore, the CORM-3 group exhibited a higher portion of normal tubules and glomeruli. TUNEL staining revealed fewer apoptotic renal tubular cells in the CORM-3 group than in the control group. The expression of 960 genes in the CORM-3 group was also altered. Pretreatment with CORM-3 before renal IRI produced a significant renoprotective effect. Fifteen of the altered genes were found to be involved in the peroxisome proliferator-activated receptors signaling pathway, and the difference in the expression of these genes between the CORM-3 and control groups was statistically significant (p<0.001).
Conclusions: CORM-3 ameliorates IRI by decreasing apoptosis and may be a novel strategy for protection against renal warm IRI.
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KEYWORD
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Carbon monoxide, Ischemia, Kidney diseases
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