Grape seed proanthocyanidin extract protects from cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis

Gao,Zhaoli; Liu,Guangyi; Hu,Zhao; Li,Xing; Yang,Xiangdong; Jiang,Bei; Li,Xianhua

doi:10.3892/mmr.2014.1883

Grape seed proanthocyanidin extract protects from cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis

Authors:
- Zhaoli Gao
- Guangyi Liu
- Zhao Hu
- Xing Li
- Xiangdong Yang
- Bei Jiang
- Xianhua Li
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Affiliations: Department of Nephrology, Qi Lu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: January 3, 2014 https://doi.org/10.3892/mmr.2014.1883
Pages: 801-807
Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Cisplatin (CP) is used as an antineoplastic drug in the clinic, but its nephrotoxicity limits its use. Grape seed proanthocyanidin extract (GSPE) is a powerful antioxidant. In this study, we investigated whether GSPE can prevent CP-induced nephrotoxicity and explored the underlying mechanism. Male C57/BL6 mice were randomly divided into four groups: control group (N), CP group (C), receiving an intraperitoneal (ip) injection of 20 mg/kg CP, GSPE group (G), receiving an intragastric (ig) dose of 500 mg/kg GSPE, and CP+GSPE group (C+G), where ig administration of GSPE was performed 30 min prior to ip injection of CP, followed by an additional ig administration of GSPE 72 h later. Blood and kidney samples were collected 120 h after treatment. The pathological changes in the kidney were examined by periodic acid-Schiff (PAS) staining, while the protein levels of glucose-regulated protein 78 (GRP78), phosphorylated‑extracellular signal-regulated kinase (p-ERK) and caspase-12 were examined by western blotting and immunohistochemical staining. Apoptosis was examined by a terminal deoxynucleotidyl transferase dUTP nick‑end labeling (TUNEL) assay. Compared to the CP group, the CP+GSPE group had a significant decrease in the level of blood urea nitrogen (BUN), serum creatinine (Scr) and reduced renal index (RI) (P<0.05), and showed limited histopathological damage. The number of TUNEL-positive cells was significantly reduced in the CP+GSPE group compared to the CP group (P<0.05), and the protein expression of GRP78, p-ERK and caspase-12 was significantly reduced in the CP+GSPE group (P<0.05). We conclude that GSPE can protect the renal function from CP-induced nephrotoxicity and can attenuate the endoplasmic reticulum (ER) stress‑induced apoptosis via regulation of the caspase-12 pathway.

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