Protection of Salvia Miltiorrhiza against aflatoxin-B1-induced hepatocarcinogenesis in Fischer 344 rats - Dual mechanisms involved

Jin Liu; Cheng Feng Yang; Shanthi Wasser; Han Ming Shen; Carolyn Eng Looi Tan; Choon Nam Ong

doi:10.1016/S0024-3205(01)01116-X

Protection of Salvia Miltiorrhiza against aflatoxin-B₁-induced hepatocarcinogenesis in Fischer 344 rats - Dual mechanisms involved

Jin Liu, Cheng Feng Yang, Shanthi Wasser, Han Ming Shen, Carolyn Eng Looi Tan, Choon Nam Ong

Markey Cancer Center / Cancer Research Priority Initiative

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

Extract of Salvia Miltiorrhiza (SM) has been widely used in traditional Chinese medicine for treating liver diseases. Recent experimental evidence indicates that it has anti-tumor potential. In this study, the effect of SM on alfatoxin B₁ (AFB₁)-induced hepatocarcinogenesis was investigated in male Fischer 344 rats. AFB₁ (40 μg/100 g body wt, by gavage) was administered once a week for 24 weeks. In SM treatment group, rats were given SM (0.25g/100g body wt, 5 days/week by gavage) for a total of 28 weeks, including 4 weeks before and 24 weeks during AFB₁ exposure. Results showed that the elevation of serum alanine aminotransferase and aspartate aminotransferase activities due to AFB₁ dosing was almost completely abolished by the treatment of SM, indicating that SM could prevent AFB₁-induced liver cell injury. It was further observed that SM substantially reduced glutathione S-transferase placenta form (GST-P) positive foci formation and GST-P mRNA expression caused by AFB₁, which clearly suggests that SM is effective in preventing AFB₁-induced hepatocarcinogenesis. Furthermore, the inhibition on AFB₁ hepatocarcinigenesis was associated with a corresponding decrease in AFB₁-DNA adducts formation as well as AFB₁-induced oxidative DNA damage (8-hydroxydeoxyguanosine) in rat liver. Our results also indicate that the protective effect of SM might be mediated through dual mechanisms: (i) the enhancement of AFB₁ detoxification pathway, especially the induction of GST-Yc2 mRNA expression, and (ii) the antioxidant property of SM.

Original language	English
Pages (from-to)	309-326
Number of pages	18
Journal	Life Sciences
Volume	69
Issue number	3
DOIs	https://doi.org/10.1016/S0024-3205(01)01116-X
State	Published - Jun 8 2001

Bibliographical note

Funding Information:
The authors would like to thank Ms. B. L. Lee for her excellent technical support with HPLC analysis; Dr. Vijayalaxmy Vijayan, Mr Ganymede Y. Lim and Ms. Regina Y. Y. Chan for their assistance with the immunohistochemical study. The authors also thank Mr. H.Y. Ong and Mr. W.X. Ding for their technical assistance. J. Liu and C.F. Yang are sponsored by research scholarships from National University of Singapore. This work was supported by a grant from the National Medical Research Council of Singapore.

Keywords

AFB-DNA adducts
Antioxidant
GST-P
GST-Yc2
Hepatocarcinogenesis
Oxidative DNA damage

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology (all)
Pharmacology, Toxicology and Pharmaceutics (all)

Access to Document

10.1016/S0024-3205(01)01116-X

Cite this

@article{c3f33ad30d3d411a9ebe54d44f12edd3,

title = "Protection of Salvia Miltiorrhiza against aflatoxin-B1-induced hepatocarcinogenesis in Fischer 344 rats - Dual mechanisms involved",

abstract = "Extract of Salvia Miltiorrhiza (SM) has been widely used in traditional Chinese medicine for treating liver diseases. Recent experimental evidence indicates that it has anti-tumor potential. In this study, the effect of SM on alfatoxin B1 (AFB1)-induced hepatocarcinogenesis was investigated in male Fischer 344 rats. AFB1 (40 μg/100 g body wt, by gavage) was administered once a week for 24 weeks. In SM treatment group, rats were given SM (0.25g/100g body wt, 5 days/week by gavage) for a total of 28 weeks, including 4 weeks before and 24 weeks during AFB1 exposure. Results showed that the elevation of serum alanine aminotransferase and aspartate aminotransferase activities due to AFB1 dosing was almost completely abolished by the treatment of SM, indicating that SM could prevent AFB1-induced liver cell injury. It was further observed that SM substantially reduced glutathione S-transferase placenta form (GST-P) positive foci formation and GST-P mRNA expression caused by AFB1, which clearly suggests that SM is effective in preventing AFB1-induced hepatocarcinogenesis. Furthermore, the inhibition on AFB1 hepatocarcinigenesis was associated with a corresponding decrease in AFB1-DNA adducts formation as well as AFB1-induced oxidative DNA damage (8-hydroxydeoxyguanosine) in rat liver. Our results also indicate that the protective effect of SM might be mediated through dual mechanisms: (i) the enhancement of AFB1 detoxification pathway, especially the induction of GST-Yc2 mRNA expression, and (ii) the antioxidant property of SM.",

keywords = "AFB-DNA adducts, Antioxidant, GST-P, GST-Yc2, Hepatocarcinogenesis, Oxidative DNA damage",

author = "Jin Liu and Yang, {Cheng Feng} and Shanthi Wasser and Shen, {Han Ming} and Tan, {Carolyn Eng Looi} and Ong, {Choon Nam}",

note = "Funding Information: The authors would like to thank Ms. B. L. Lee for her excellent technical support with HPLC analysis; Dr. Vijayalaxmy Vijayan, Mr Ganymede Y. Lim and Ms. Regina Y. Y. Chan for their assistance with the immunohistochemical study. The authors also thank Mr. H.Y. Ong and Mr. W.X. Ding for their technical assistance. J. Liu and C.F. Yang are sponsored by research scholarships from National University of Singapore. This work was supported by a grant from the National Medical Research Council of Singapore.",

year = "2001",

month = jun,

day = "8",

doi = "10.1016/S0024-3205(01)01116-X",

language = "English",

volume = "69",

pages = "309--326",

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TY - JOUR

T1 - Protection of Salvia Miltiorrhiza against aflatoxin-B1-induced hepatocarcinogenesis in Fischer 344 rats - Dual mechanisms involved

AU - Liu, Jin

AU - Yang, Cheng Feng

AU - Wasser, Shanthi

AU - Shen, Han Ming

AU - Tan, Carolyn Eng Looi

AU - Ong, Choon Nam

N1 - Funding Information: The authors would like to thank Ms. B. L. Lee for her excellent technical support with HPLC analysis; Dr. Vijayalaxmy Vijayan, Mr Ganymede Y. Lim and Ms. Regina Y. Y. Chan for their assistance with the immunohistochemical study. The authors also thank Mr. H.Y. Ong and Mr. W.X. Ding for their technical assistance. J. Liu and C.F. Yang are sponsored by research scholarships from National University of Singapore. This work was supported by a grant from the National Medical Research Council of Singapore.

PY - 2001/6/8

Y1 - 2001/6/8

N2 - Extract of Salvia Miltiorrhiza (SM) has been widely used in traditional Chinese medicine for treating liver diseases. Recent experimental evidence indicates that it has anti-tumor potential. In this study, the effect of SM on alfatoxin B1 (AFB1)-induced hepatocarcinogenesis was investigated in male Fischer 344 rats. AFB1 (40 μg/100 g body wt, by gavage) was administered once a week for 24 weeks. In SM treatment group, rats were given SM (0.25g/100g body wt, 5 days/week by gavage) for a total of 28 weeks, including 4 weeks before and 24 weeks during AFB1 exposure. Results showed that the elevation of serum alanine aminotransferase and aspartate aminotransferase activities due to AFB1 dosing was almost completely abolished by the treatment of SM, indicating that SM could prevent AFB1-induced liver cell injury. It was further observed that SM substantially reduced glutathione S-transferase placenta form (GST-P) positive foci formation and GST-P mRNA expression caused by AFB1, which clearly suggests that SM is effective in preventing AFB1-induced hepatocarcinogenesis. Furthermore, the inhibition on AFB1 hepatocarcinigenesis was associated with a corresponding decrease in AFB1-DNA adducts formation as well as AFB1-induced oxidative DNA damage (8-hydroxydeoxyguanosine) in rat liver. Our results also indicate that the protective effect of SM might be mediated through dual mechanisms: (i) the enhancement of AFB1 detoxification pathway, especially the induction of GST-Yc2 mRNA expression, and (ii) the antioxidant property of SM.

AB - Extract of Salvia Miltiorrhiza (SM) has been widely used in traditional Chinese medicine for treating liver diseases. Recent experimental evidence indicates that it has anti-tumor potential. In this study, the effect of SM on alfatoxin B1 (AFB1)-induced hepatocarcinogenesis was investigated in male Fischer 344 rats. AFB1 (40 μg/100 g body wt, by gavage) was administered once a week for 24 weeks. In SM treatment group, rats were given SM (0.25g/100g body wt, 5 days/week by gavage) for a total of 28 weeks, including 4 weeks before and 24 weeks during AFB1 exposure. Results showed that the elevation of serum alanine aminotransferase and aspartate aminotransferase activities due to AFB1 dosing was almost completely abolished by the treatment of SM, indicating that SM could prevent AFB1-induced liver cell injury. It was further observed that SM substantially reduced glutathione S-transferase placenta form (GST-P) positive foci formation and GST-P mRNA expression caused by AFB1, which clearly suggests that SM is effective in preventing AFB1-induced hepatocarcinogenesis. Furthermore, the inhibition on AFB1 hepatocarcinigenesis was associated with a corresponding decrease in AFB1-DNA adducts formation as well as AFB1-induced oxidative DNA damage (8-hydroxydeoxyguanosine) in rat liver. Our results also indicate that the protective effect of SM might be mediated through dual mechanisms: (i) the enhancement of AFB1 detoxification pathway, especially the induction of GST-Yc2 mRNA expression, and (ii) the antioxidant property of SM.

KW - AFB-DNA adducts

KW - Antioxidant

KW - GST-P

KW - GST-Yc2

KW - Hepatocarcinogenesis

KW - Oxidative DNA damage

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