Protective effect of curcumin against cyclosporine A‑induced rat nephrotoxicity

Huang,Jianjun; Yao,Xuping; Weng,Guobin; Qi,Honggang; Ye,Xiaolei

doi:10.3892/mmr.2018.8591

Protective effect of curcumin against cyclosporine A‑induced rat nephrotoxicity

Authors:
- Jianjun Huang
- Xuping Yao
- Guobin Weng
- Honggang Qi
- Xiaolei Ye
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Affiliations: Department of Urology, Ningbo Urology and Nephrology Hospital, Ningbo University, Ningbo, Zhejiang 315100, P.R. China, Ningbo Institute of Medical Sciences, Ningbo University, Ningbo, Zhejiang 315100, P.R. China
Published online on: February 12, 2018 https://doi.org/10.3892/mmr.2018.8591
Pages: 6038-6044

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Abstract

This study explored the potential value of curcumin, a natural product, in the protection of CsA‑induced nephrotoxicity. The aim of the present study was to investigate the effects of curcumin on Cyclosporine A (CsA)‑induced renal oxidative stress and determine the potential underlying molecular mechanisms of the renal protective effects of Cur. HK‑2 human renal cells were co‑treated with CsA and various doses of Cur. Cell survival rate was determined by an MTT assay, total cellular protein was collected and oxidative stress in cell homogenates was evaluated by determining the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH‑Px) and catalase (CAT), the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), and total antioxidant capacity. Furthermore, Bcl‑2 and Bcl‑2‑associated X (Bax) protein expression was measured by western blot analysis. In addition, a CsA‑induced nephrotoxicity (CAN) rat model was also established. Renal function was analyzed by measuring creatinine (Crea) and blood urea nitrogen (BUN) in the serum of rats, and histopathological examination was performed on renal tissues using hematoxylin and eosin staining, periodic acid‑Schiff staining and nuclear factor‑κB (NF‑κB) immunostaining. The results demonstrated that treatment of HK‑2 cells with CsA significantly increased ROS and MDA levels, and decreased the activities of SOD, GSH‑Px and CAT, compared with the control group. However, these effects of CsA were dose‑dependently improved by treatment with Cur. In addition, Cur treatment increased Bcl‑2 and decreased Bax protein in HK‑2 cells, compared with cells treated with CsA alone. In the CAN rat model CsA (30 mg/kg) treatment significantly elevated serum Crea levels and BUN, but lowered endogenous Crea clearance rate, compared with the control group. Co‑administration of Cur with CsA significantly reversed the effects of CsA on serum Crea levels, BUN and Crea clearance rate (Ccr). Additionally, Cur alleviated CsA‑induced renal cell injury, as less vacuolar degeneration of glomerular cells was observed compared with the CsA alone group. In conclusion, Cur may increase renal antioxidant capacity and reduce the Bax/Bcl‑2 ratio, subsequently improving CsA‑induced renal failure and renal tubular deformation and cell vacuolization.

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