The Effect of Cobalt Chloride Pre-treatment on Experimental Ischemia-Reperfusion Renal Injury / 대한신장학회잡지

ABSTRACT

BACKGOUND Cobalt chloride (COCL) has hypoxia-mimetic effects by inhibiting degradation of HIF-1alpha, which is a master regulator of genes activated by low oxygen tension. Heme oxygenase-1 (HO-1), an inducible heat shock protein, is known to have cytoprotective effects against ischemic injury. This study evaluated the efficacy of COCL in a bilateral renal ischemia-reperfusion (I-R) injury model of male Sprague-Dawley rats. METHODS: I-R renal injury was induced by 45 min clamping of both renal arteries. Rats in the sham (n=6) and I-R control groups (n=8) had been drinking tap water, whereas rats in the COCL treated sham (n=6) and COCL treated I-R groups (n=9) had been drinking water containing 2 mM COCL from day -10 to day 1. RESULTS: The serum level of creatinine 24 hrs after surgery was 2.6+/-1.1 (mean+/-SD) mg/dL in I-R COCL treated group, significantly lower than that in I-R control group (4.8+/-1.6 mg/dL, p<0.05). The renal HO-1 gene expression and protein signal were significantly upregulated in the COCL treated sham group compared to sham operated control rats (all, p<0.05). The expressions of TGF-beta MCP-1, TNF-alpha endothelin-1 and Fas genes in COCL treated I-R rats were significantly lower than those of I-R control rats (all, p<0.05). The level of Bcl-2 gene expression of COCL treated I-R rats was significantly higher than the level of I-R control rats (p<0.05). CONCLUSION: It is speculated that the pretreatment of COCL in I-R rat model attenuates ischemic renal injury and at least in part, upregulation of renal HO-1 is involved in this mechanism.