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. 2022 Jun 15;37(3):e370305.
doi: 10.1590/acb370305. eCollection 2022.

Protective effect of hydroxysafflor yellow A on cyclosporin A-induced renal oxidative stress in vitro and in vivo

Jiyuan Wang  1 , Yu Chen  1
Affiliations

Protective effect of hydroxysafflor yellow A on cyclosporin A-induced renal oxidative stress in vitro and in vivo

Jiyuan Wang et al. Acta Cir Bras. .

Abstract

Purpose: To explore the mechanism and investigate the protective effect of hydroxysafflor yellow A (HSYA) on renal oxidative stress, which cyclosporine A (CsA) induces.

Methods: HK-2 cells were treated with CsA to get CsA-induced oxidative stress. The effects on oxidative stress and apoptosis of HK-2 cells were detected. The contents of SOD, MDA, GSH-Px, ROS, and CAT in serum were measured, and the expression of apoptosis-related proteins was detected by western blot. Then, established the renal oxidative stress injury rats to verify the efficacy of HSYA.

Results: HSYA could reduce the ROS and MDA contents induced by CsA. Compared with the CsA group, the activities of SOD, CAT, and GSH-Px increased significantly when treated with HSYA. HSYA could inhibit CsA-induced apoptosis in HK-2 cells, and promote the protein of Bcl-2 and inhibit the expression of Bax. Animal experiments showed that HSYA could reduce CsA-induced renal cell injury by reducing glomerular cell vacuoles and inflammatory factors in tissues. It also decreased serum creatinine (Crea) and blood urea nitrogen, increased Crea clearance significantly.

Conclusions: HSYA could significantly improve the antioxidant capacity of the kidney cells and inhibit cell apoptosis, thereby effectively ameliorating CsA-induced oxidative stress in vitro and in vivo.

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Conflict of interest statement

Conflict of interest: Nothing to declare.

Figures

Figure 1
Figure 1. The effects of HSYA at different concentrations on HK-2 cell viability, oxidative stress-related factors and antioxidant enzyme activities. (a) MTT assay for measuring the survival rate of cells to assess the effect of HSYA on HK-2 cells; (b) The effect of HSYA on amount of ROS produced by HK-2 cells; (c) Changes of MDA production in HK-2 cells under different concentrations of HSYA supplementation; (d) Changes of SOD activity in HK-2 cells under different concentrations of HSYA supplementation; (e) Changes of activity of GSH-Px in HK-2 cells under different concentrations of HSYA supplementation; (f) The effect of different concentrations of HSYA on CAT activity in HK-2 cells. Compared with cells treated with CsA only, *p < 0.05 and **p < 0.01, compared with control, #p < 0.05 and ##p < 0.01.
Figure 2
Figure 2. The effect of HSYA at different concentrations on HK-2 cell apoptosis and the expression of apoptosis-related proteins. (a) The effect of HSYA on apoptosis of HK-2 cell which was induced by CsA; (b) The effect of HSYA on the Bcl-2 and Bax protein expression levels in HK-2 cells; (c) Determine the effect of HSYA on the ratio of Bax/Bcl-2 in CsA-induced HK-2 cells by densitometric analysis. Compared with cells treated with CsA only, *p < 0.05 and **p < 0.01, compared with control, ##p < 0.01.
Figure 3
Figure 3. The effect of HSYA on the CsA-induced CAN rat model. Renal PAS staining showed that administration of HSYA reduced renal fibrosis in CsA-treated rats. Arrows indicate positive PAS staining. Kidney H&E staining showed that the structure of CsA treated rat kidney was improved after HSYA administration. Immunostaining of NF-κB indicated that HSYA reduced the inflammatory response in CsA-treated rats (PAS; NF-κB). The number of rats in each group is 6.
Figure 4
Figure 4. Effects of HSYA on the renal function indexes of rats induced by CsA. Compared with the group treated with CsA only, the number of rats in each group is 6. *p < 0.05, **p < 0.01; compared with control, #p < 0.05, ##p < 0.01.
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