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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
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, Qi Lu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
    Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 801-807
    |
    Published online on: January 3, 2014
       https://doi.org/10.3892/mmr.2014.1883
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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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Copy and paste a formatted citation
Spandidos Publications style
Gao Z, Liu G, Hu Z, Li X, Yang X, Jiang B and Li X: Grape seed proanthocyanidin extract protects from cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis. Mol Med Rep 9: 801-807, 2014.
APA
Gao, Z., Liu, G., Hu, Z., Li, X., Yang, X., Jiang, B., & Li, X. (2014). Grape seed proanthocyanidin extract protects from cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis. Molecular Medicine Reports, 9, 801-807. https://doi.org/10.3892/mmr.2014.1883
MLA
Gao, Z., Liu, G., Hu, Z., Li, X., Yang, X., Jiang, B., Li, X."Grape seed proanthocyanidin extract protects from cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis". Molecular Medicine Reports 9.3 (2014): 801-807.
Chicago
Gao, Z., Liu, G., Hu, Z., Li, X., Yang, X., Jiang, B., Li, X."Grape seed proanthocyanidin extract protects from cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis". Molecular Medicine Reports 9, no. 3 (2014): 801-807. https://doi.org/10.3892/mmr.2014.1883
Copy and paste a formatted citation
x
Spandidos Publications style
Gao Z, Liu G, Hu Z, Li X, Yang X, Jiang B and Li X: Grape seed proanthocyanidin extract protects from cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis. Mol Med Rep 9: 801-807, 2014.
APA
Gao, Z., Liu, G., Hu, Z., Li, X., Yang, X., Jiang, B., & Li, X. (2014). Grape seed proanthocyanidin extract protects from cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis. Molecular Medicine Reports, 9, 801-807. https://doi.org/10.3892/mmr.2014.1883
MLA
Gao, Z., Liu, G., Hu, Z., Li, X., Yang, X., Jiang, B., Li, X."Grape seed proanthocyanidin extract protects from cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis". Molecular Medicine Reports 9.3 (2014): 801-807.
Chicago
Gao, Z., Liu, G., Hu, Z., Li, X., Yang, X., Jiang, B., Li, X."Grape seed proanthocyanidin extract protects from cisplatin-induced nephrotoxicity by inhibiting endoplasmic reticulum stress-induced apoptosis". Molecular Medicine Reports 9, no. 3 (2014): 801-807. https://doi.org/10.3892/mmr.2014.1883
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