Investig Clin Urol.  2020 Jul;61(4):441-451. 10.4111/icu.2020.61.4.441.

Carbon monoxide–releasing molecule-3: Amelioration of renal ischemia reperfusion injury in a rat model

Affiliations
  • 1Department of Urology, CHA Fertility Center Seoul Station, CHA University School of Medicine, Seoul, Korea
  • 2Department of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
  • 3Department of Urology, Hanyang University College of Medicine, Seoul, Korea

Abstract

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.

Keyword

Carbon monoxide; Ischemia; Kidney diseases
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