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The hepatocarcinogenic effects of aristolochic acid I and associated mechanisms in C3H/HeN suckling mice
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Ting WANG1, Wen-xiao WU1, 2, Zhi LIN1, Chao WANG1, Yan-wei YANG1, Yu-fa MIAO1, Xing-chao GENG1, Bo LI3
Chinese Journal of New Drugs | 2021, 30(13) : 1168 - 1175
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Chinese Journal of New Drugs | 2021, 30(13): 1168-1175
The hepatocarcinogenic effects of aristolochic acid I and associated mechanisms in C3H/HeN suckling mice
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Ting WANG1, Wen-xiao WU1, 2, Zhi LIN1, Chao WANG1, Yan-wei YANG1, Yu-fa MIAO1, Xing-chao GENG1, Bo LI3
Affiliations
  • 1National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing 100176, China
  • 2Peking Union Medical College, Beijing 100005, China
  • 3National Institutes for Food and Drug Control, Beijing 100050, China
Published: 2021-07-15
Outline
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Objective:

To explore the potential hepatocarcinogenic effect of aristolochic acid I (AAI) on 2-week-old C3H/HeN suckling mice and its possible mechanism.

Methods:

Two-week-old C3H/HeN suckling mice were randomly divided into 3 groups, i.e., the vehicle control group (0.5% CMC-Na), the liver cancer positive agent model group (DEN 20 mg·kg-1) and the AAI group (AAI 10 mg·kg-1). After 9 months of observation after a single administration, the organs were taken for gross pathological and histopathological examination, and the levels of serum biochemical indicators such as ALT, AST and AFP in mice were detected. At the same time, the contents of IL-1β and IL-6, the expression of Ki67, CK19, NF-κB P65, Ras, Raf, and caspase-3 in mouse liver were detected.

Results:

In this experiment, AAI caused liver cancer in C3H/HeN suckling mice. The incidence of liver cancer in male and female mice were 78.57% and 41.67%, respectively. Compared with the vehicle control group, the levels of ALT, AST, AFP, IL-1β and IL-6 in the AAI group were significantly increased, and the expression of Ki67 and CK19 in liver were positive. The results of Western blot showed that AAI significantly increased the expression of NF-κB P65, P-AKT, Ras, C-Jun, C-Fos, C-MYC and Bcl-2, and significantly decreased the expression of IKBα, Bax and Caspase-3.

Conclusion:

In this experiment, AAI caused liver cancer in 2-week-old C3H/HeN suckling mice. The mechanism may be related to the activation of PI3K/AKT inflammatory pathway in hepatocytes, Ras/AP1/C-MYC proliferation pathway and the inhibition of Bax/Bcl-2/Caspase-3 Mitochondrial apoptosis pathway.

aristolochic acid I  /  liver cancer  /  C3H/HeN suckling mice
王婷, 吴文晓, 林志, 王超, 杨艳伟, 苗玉发, 耿兴超, 李波. 马兜铃酸I致C3H/HeN乳鼠肝癌及机制探索. 中国新药杂志, 2021 , 30 (13) : 1168 -1175 .
Ting WANG, Wen-xiao WU, Zhi LIN, Chao WANG, Yan-wei YANG, Yu-fa MIAO, Xing-chao GENG, Bo LI. The hepatocarcinogenic effects of aristolochic acid I and associated mechanisms in C3H/HeN suckling mice[J]. Chinese Journal of New Drugs, 2021 , 30 (13) : 1168 -1175 .
Year 2021 volume 30 Issue 13
30
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  • Online Date:2026-10-30
  • Published:2021-07-15
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  • Accepted:2021-03-25
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Affiliations
    1National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, Beijing 100176, China
    2Peking Union Medical College, Beijing 100005, China
    3National Institutes for Food and Drug Control, Beijing 100050, China
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表12种不同金属材料的力学参数
科
Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)
属
Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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