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Cell Biochem Biophys. 2019 Dec;77(4):367-377. doi: 10.1007/s12013-019-00890-5. Epub 2019 Oct 28.

Grape Seed Procyanidins Attenuates Cisplatin-induced Human Embryonic Renal Cell Cytotoxicity by Modulating Heme Oxygenase-1 in Vitro.

Han H1,2, Wang H1,2, Du Y1,2, Gao L3,4.

Author information

1
College of Biochemical Engineering, Beijing Union University, Beijing, 100023, China.
2
Beijing Municipal Key Laboratory of Biologically Active Substances and Functional Food, Beijing, 100191, China.
3
College of Biochemical Engineering, Beijing Union University, Beijing, 100023, China. lipinggao62@163.com.
4
Beijing Municipal Key Laboratory of Biologically Active Substances and Functional Food, Beijing, 100191, China. lipinggao62@163.com.

Abstract

Cisplatin is a widely used anti-cancer drug. However, cisplatin is limited in clinical treatment because of its severe nephrotoxicity. This study reported whether O-GSP can antagonize the cisplatin-induced cytotoxicity in HEK293 cells through inducing HO-1 protein expression. We previously demonstrated O-GSP can increase the survival rate of HEK293 and have protective effect on HEK293 cells. Herein, We found that O-GSP can antagonize cisplatin nephrotoxicity through regulating the expression of HO-1. O-GSP promotes the translocation of Nrf2 in the nucleus, and activates the ERKN JNK pathway and p38 MAPK pathway. Interestingly, p38 MAPK plays a major role in HO-1 expression induced by O-GSP. And O-GSP can modulate the decrease of Nrf2 and HO-1 expression induced by cisplatin, and improve the cisplatin-induced activity and apoptosis rate of cells by stimulating the expression of HO-1. However, the protective effects of O-GSP are inhibited by ZnPP IX. Collectively, the results indicated that O-GSP induced the expression of HO-1 through p38MAPK and Nrf2 pathway in HEK293 cells.

KEYWORDS:

Cisplatin; HO-1; Nephrotoxicity; Nrf2; Oligomeric grape seed procyanidins

PMID:
31659617
DOI:
10.1007/s12013-019-00890-5

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