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Mechanisms Underlying the Protective Effect of Saponins Extracted from Fermented Codonopsis lanceolata against Oxidative DNA Damage Induced by Diethylnitrosamine in Liver Cells of Mice

YU Xing1,ZHENG Chun-ji1,HAN Chun-ji1,2,*,JIANG Guo-zhe1,CUI Cheng-bi2   

  1. 1. Department of Preventive Medicine, College of Medicine, Yanbian University, Yanji 133002, China;
    2. Food Research Center, Yanbian University, Yanji 133002, China
  • Online:2013-09-15 Published:2013-09-27
  • Contact: HAN Chun-ji

Abstract:

Objective: To explore the mechanisms by which saponins extracted from fermented Codonopsis lanceolata
(FCLS) protect against oxidative DNA damage induced by diethylnitrosamine (DEN) in mouse liver cells and consequently
provide useful references for chemical prevention of liver cancer. Methods: Fifty mice were randomly divided into five
groups including negative control group (intragastric administration of 10 mL of distilled water per kg body weight), DEN
group (intraperitoneal injection of DEN at a dose of 20 mg/kg every other day), and high, middle and low dose FCLS groups
(intragastric administration of FCLS at doses of 200, 100, 50 mg/(kg·d), and intraperitoneal injection of DEN at a dose
of 20 mg/kg every other day). The administration period for all the treatments was 6 weeks. The contents of 8-hydroxyl
deoxyguanosine (8-OHdG) and the activity of 8-hydroxy guanine-DNA glycosylase (OGG1) in mouse hepatic tissue were
determined by ELISA, and cytochrome P4502E1 (CYP2E1) protein expression was analyzed by immunohistochemical
method. Results: The 8-OHdG content and CYP2E1 protein expression in liver tissue from the DEN group were significantly
increased when compared with those from the negative control group (P < 0.01), and OGG1 activity in the DEN group was
significantly decreased when compared with the control group (P < 0.01). The 8-OHdG content of liver tissue in the high
and middle dose FCLS groups were significantly lower than that of DEN group (P < 0.01), and increasing the FCLS dose
resulted in a lower 8-OHdG content in the FCLS treatment groups. OGG1 content in liver tissue from the DEN group was
obviously lower than that from the negative control group (P < 0.05). OGG1 content in liver tissue from the three FCLS
groups were significantly higher than that from the DEN group (P < 0.05 or P < 0.01). The dose of FCLS revealed an obvious dependent relationship with the activity of OGG1. CYP2E1 protein expression in the FCLS middle and high dose groups
were significantly lower than that from the DEN group (P < 0.05 or P < 0.01). Conclusion: The protective effect of saponins
from fermented Codonopsis lanceolata against oxidative DNA damage induced by DEN may be related to the increased activity of
antioxidant enzymes and DNA damage repair enzymes, and reduced activity of metabolic enzymes for drugs.

Key words: fermentation, Codonopsis lanceolata, diethylnitrosamine, oxidative DNA damage, mice

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