Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Jul 15;7(8):4607-16.
eCollection 2014.

Epigallocatechin-3-gallate protects against cisplatin nephrotoxicity by inhibiting the apoptosis in mouse

Peimei Zou  1 , Jian Song  1 , Bei Jiang  1 , Fei Pei  1 , Binbin Chen  1 , Xiangdong Yang  1 , Guangyi Liu  2 , Zhao Hu  1
Affiliations

Epigallocatechin-3-gallate protects against cisplatin nephrotoxicity by inhibiting the apoptosis in mouse

Peimei Zou et al. Int J Clin Exp Pathol. .

Abstract

Cisplatin (CP) is a commonly used anticancer drug, but its notable side effect of nephrotoxicity limits its use in clinic. Epigallocatechin-3-gallate (EGCG), an anti-oxidant, anti-inflammatory, and anti-tumorigenic green tea polyphenol, has been available on the market for its beneficial effects. The aim of this study was to investigate whether EGCG can prevent the nephrotoxic effect of CP and the involved mechanisms. Male C57/BL6 mice were randomly divided into four groups: control group, EGCG group, CP group, and CP+EGCG group. On day 5, mice were sacrificed. Our results showed that EGCG treatment significantly ameliorated the histopathological changes and the increased serum creatinine and blood urea nitrogen (BUN) induced by CP. TUNEL-positive cells significantly reduced in the CP+EGCG group compared with CP group. EGCG also inhibited the expression of the ligand of death receptor Fas (Fas-L), apoptosis regulator BAX (Bax) and tumor-suppressor protein p53, and increased the expression of B-cell lymphoma 2 (Bcl-2). These findings suggest that EGCG can ameliorate CP-induced apoptosis in the kidney by regulating death receptor Fas conducted extrinsic pathway, and the expression of Bax and Bcl-2.

Keywords: Cisplatin (CP); Epigallocatechin-3-gallate (EGCG); apoptosis; mouse; renal.

PubMed Disclaimer

Figures

Figure 1
Figure 1
EGCG attenuated the kidney histological abnormalities induced by CP in mice. Mice were treated with vehicle (A), EGCG (B), CP (C), and CP+EGCG (D), separately. In CP group, renal tubular atrophy and dilation, necrosis and desquamation of renal tubular epithelial cells, and intratubular cast formation in the proximal tubules of kidney were obvious. Tubular damage was greatly improved in CP+EGCG group. Tubular injury score (E). Data are presented as means ± SD. *p<0.05 versus control group; #p<0.05 versus CP group. Original magnification, ×400.
Figure 2
Figure 2
EGCG inhibits the apoptosis of renal tubular epithelial cells induced by CP. Mice were treated with vehicle (A), EGCG (B), CP (C), and CP+EGCG (D), separately. Red staining represents TUNEL‑positive cells. Original magnification, ×400. The percentage of TUNEL-positive cells in different groups (E). Data are presented as means ± SD. *p<0.05 versus control group; #p<0.05 versus CP group.
Figure 3
Figure 3
Immunohistochemical of Fas-L in the kidney of mouse. Mice were treated with vehicle (A), EGCG (B), CP (C), and CP+EGCG (D), separately. The brown granules represent positively stained cells. Original magnification, ×400. Measurement of the intensity of Fas-L immunostaining (E). Western blot analysis of Fas-L (F), and quantification of corresponding protein level (G). Data are presented as means ± SD. *p<0.05 versus control group; #p<0.05 versus CP group.
Figure 4
Figure 4
Immunohistochemical detection of Bax and Bcl-2: Mice were treated with vehicle (A, E), EGCG (B, F), CP (C, G), and CP+EGCG (D, H), separately. The brown granules represent positively stained cells. Original magnification, ×400. Measurement of the intensity of Bax (I) and Bcl-2 (J) immunostaining. Data are presented as means ± SD. *p<0.05 versus control group; #p<0.05 versus CP group.
Figure 5
Figure 5
Western blot analysis of Bax and Bcl-2 (A), and quantification of the protein levels (B, C). Mice treated with vehicle, EGCG, CP, and CP+EGCG. Data are expressed as mean ± SD. *p<0.05 versus control group; #p<0.05 versus CP group.
Figure 6
Figure 6
Western blot analysis of p53 (A) and quantification of the protein level (B). Mice treated with vehicle, EGCG, CP, and CP+EGCG. Data are expressed as mean ± SD. *p<0.05 versus control group; #p<0.05 versus CP group.
Figure 7
Figure 7
The possible mechanism of the protect effect of EGCG to the nephrotoxicity induced by CP in mouse.
See this image and copyright information in PMC

References

    1. Hartmann JT, Fels LM, Knop S, Stolt H, Kanz L, Bokemeyer C. A randomized trial comparing the nephrotoxicity of cisplatin/ifosfamide-based combination chemotherapy with or without amifostine in patients with solid tumors. Invest New Drugs. 2000;18:281–289. - PubMed
    1. Hartmann JT, Lipp HP. Toxicity of platinum compounds. Expert Opin Pharmacother. 2003;4:889–901. - PubMed
    1. Arany I, Safirstein RL. Cisplatin nephrotoxicity. Semin Nephrol. 2003;23:460–464. - PubMed
    1. Sastry J, Kellie SJ. Severe neurotoxicity, ototoxicity and nephrotoxicity following high-dose cisplatin and amifostine. Pediatr Hematol Oncol. 2005;22:441–445. - PubMed
    1. Choi YJ, Baranowska-Daca E, Nguyen V, Koji T, Ballantyne CM, Sheikh-Hamad D, Suki WN, Truong LD. Mechanism of chronic obstructive uropathy: increased expression of apoptosis-promoting molecules. Kidney Int. 2000;58:1481–1491. - PubMed

Publication types

LinkOut - more resources