Abstract
Objective Contrast-induced acute kidney injury (CI-AKI) is a serious side effect of contrast media use. The purpose of this study was to investigate the role and mechanism of tolvaptan (TOL) in CI-AKI. Methods 24 Wistar male rats were randomly divided into 4 groups (n = 6). And a rat model of CI-AKI was established. Then, the blood and urine of rats in each group were collected to detect relevant parameters. HE staining was utilized for the observation of the pathological changes of rat kidney tissues, TUNEL assay for the detection of tubular cell apoptosis, biochemical detection for the confirmation of oxidative stress level in kidney tissues, and western blot for the test of the expression of apoptotic proteins and the Nrf2 signaling pathway-related proteins in kidney tissues. Results TOL could significantly reduce the serum level of urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decrease serum Cys-C and urine KIM-1 in CI-AKI rats. The result above meant that TOL could improve kidney injury and reduce tubular cell apoptosis in CI-AKI rats. In addition, TOL contributed to a reduction of oxidative stress level by downregulating myeloperoxidase level and increasing the activities of superoxide dismutase and glutathione peroxidase in the kidney tissue of CI-AKI rats. After the pretreatment of TOL, the expression of proapoptotic proteins cleaved-caspase 3 and BAX, as well as mitochondrial fusion proteins DRP1 and MFN2 was downregulated, while the expression of Bcl-2 and PINK1 was upregulated in the kidney tissue of CI-AKI rats. Further, TOL could activate the Nrf2 signaling pathway, and the Nrf2 inhibitor ML385 reversed the effect of TOL on CI-AKI. Conclusion TOL can improve CI-AKI by activating the Nrf2/HO-1 signaling pathway, inhibiting oxidative stress response, and reducing tubular cell apoptosis.
Highlights
Contrast-induced acute kidney injury (CI-AKI), known as contrast-induced nephropathy (CIN), refers to an acute renal complication occurring after the application of contrast media
HE staining was utilized for the observation of the pathological changes of rat kidney tissues, TdT-Mediated dUTP-Biotin Nick End Labeling (TUNEL) assay for the detection of tubular cell apoptosis, biochemical detection for the confirmation of oxidative stress level in kidney tissues, and western blot for the test of the expression of apoptotic proteins and the Nrf2 signaling pathway-related proteins in kidney tissues
The results showed (Figures 2(a)–2(e)) that serum level of blood urea nitrogen (BUN), Cr, neutrophil gelatinase-associated lipocalin (NGAL), and Cys-C and urinary level of KIM-1 were significantly increased in the CIN group compared with the control group (P < 0:05)
Summary
Contrast-induced acute kidney injury (CI-AKI) is a serious side effect of contrast media use. HE staining was utilized for the observation of the pathological changes of rat kidney tissues, TUNEL assay for the detection of tubular cell apoptosis, biochemical detection for the confirmation of oxidative stress level in kidney tissues, and western blot for the test of the expression of apoptotic proteins and the Nrf signaling pathway-related proteins in kidney tissues. The result above meant that TOL could improve kidney injury and reduce tubular cell apoptosis in CI-AKI rats. TOL contributed to a reduction of oxidative stress level by downregulating myeloperoxidase level and increasing the activities of superoxide dismutase and glutathione peroxidase in the kidney tissue of CI-AKI rats. TOL can improve CI-AKI by activating the Nrf2/HO-1 signaling pathway, inhibiting oxidative stress response, and reducing tubular cell apoptosis
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