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Resveratrol Downregulates Cyp2e1 and Attenuates Chemically Induced Hepatocarcinogenesis in SD Rats.

Wu X, Li C, Xing G, Qi X, Ren J - J Toxicol Pathol (2013)

Bottom Line: By immunohistochemical staining of serial liver sections, we found that the expression of Cyp2e1 in GST-P-positive foci showed three distinct patterns: decreased in GST-P foci, increased in GST-P foci when compared with surrounding liver tissue and mixed type.The number of GST-P foci with increased Cyp2e1 expression was greater than the number of GST-P foci with decreased Cyp2e1.REV or DADS significantly reduced the expression of GST-P and Cyp2e1 in both foci and surrounding liver tissue.

View Article: PubMed Central - PubMed

Affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China.

ABSTRACT
Cyp2e1 plays an important role in chemically induced hepatocarcinogenesis. Resveratrol (REV) is known to prevent diethylnitrosamine (DEN)-induced hepatocarcinogenesis, but its effects on this process induced by DEN and 2-acetylaminofluorene (2-AAF) and the role of Cyp2e1 remain unclear. In this study, glutathione S-transferase placental form (GST-P)-positive foci were used as a marker of hepatocarcinogenesis. REV or diallyl disulfide (DADS, an inhibitor of Cyp2e1) significantly reduced both the area and number of GST-P-positive foci induced by DEN and 2-AAF. Treatment with REV or DADS also markedly decreased the expression of Cyp2e1 in the rat liver. By immunohistochemical staining of serial liver sections, we found that the expression of Cyp2e1 in GST-P-positive foci showed three distinct patterns: decreased in GST-P foci, increased in GST-P foci when compared with surrounding liver tissue and mixed type. The number of GST-P foci with increased Cyp2e1 expression was greater than the number of GST-P foci with decreased Cyp2e1. Protein levels of GST-P and Cyp2e1 were also higher in foci compared with surrounding liver tissue. REV or DADS significantly reduced the expression of GST-P and Cyp2e1 in both foci and surrounding liver tissue. Taken together, these results suggested that REV has a significant inhibitory effect on chemically induced hepatocarcinogenesis, which may be attributed to downregulation of Cyp2e1.

No MeSH data available.


Related in: MedlinePlus

Comparison of GST-P and Cyp2e1 expression between GST-P foci and the surrounding liver tissue. To ensure all types of GST-P foci will be collected, most of the GST-P-positive foci and surrounding GST-P/Cyp2e1-negative liver tissue in one section are dissected. (A) Western blot analysis of levels of GST-P and Cyp2e1 protein in foci and surrounding tissues (non-foci). (B, C) Semiquantitative analysis of GST-P (B) and Cyp2e1 (C) protein levels in foci and surrounding tissues (non-foci, negative staining for GST-P and Cyp2e1). The levels of GST-P and Cyp2e1 protein were normalized to β-actin. Each bar represents the mean±SD. (n=6). * P<0.05; ** P<0.01 compared with the level of protein in foci of the DEN→2-AAF group. F, foci; NF, non-foci.
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fig_005: Comparison of GST-P and Cyp2e1 expression between GST-P foci and the surrounding liver tissue. To ensure all types of GST-P foci will be collected, most of the GST-P-positive foci and surrounding GST-P/Cyp2e1-negative liver tissue in one section are dissected. (A) Western blot analysis of levels of GST-P and Cyp2e1 protein in foci and surrounding tissues (non-foci). (B, C) Semiquantitative analysis of GST-P (B) and Cyp2e1 (C) protein levels in foci and surrounding tissues (non-foci, negative staining for GST-P and Cyp2e1). The levels of GST-P and Cyp2e1 protein were normalized to β-actin. Each bar represents the mean±SD. (n=6). * P<0.05; ** P<0.01 compared with the level of protein in foci of the DEN→2-AAF group. F, foci; NF, non-foci.

Mentions: GST-P-positive foci and the surrounding liver tissue were dissected and collected to detect the levels of GST-P and Cyp2e1 proteins. To ensure all types of GST-P foci will be collected, most of the GST-P-positive foci and surrounding GST-P/Cyp2e1-negative liver tissue in one section are dissected. As shown in Fig. 5Fig. 5.


Resveratrol Downregulates Cyp2e1 and Attenuates Chemically Induced Hepatocarcinogenesis in SD Rats.

Wu X, Li C, Xing G, Qi X, Ren J - J Toxicol Pathol (2013)

Comparison of GST-P and Cyp2e1 expression between GST-P foci and the surrounding liver tissue. To ensure all types of GST-P foci will be collected, most of the GST-P-positive foci and surrounding GST-P/Cyp2e1-negative liver tissue in one section are dissected. (A) Western blot analysis of levels of GST-P and Cyp2e1 protein in foci and surrounding tissues (non-foci). (B, C) Semiquantitative analysis of GST-P (B) and Cyp2e1 (C) protein levels in foci and surrounding tissues (non-foci, negative staining for GST-P and Cyp2e1). The levels of GST-P and Cyp2e1 protein were normalized to β-actin. Each bar represents the mean±SD. (n=6). * P<0.05; ** P<0.01 compared with the level of protein in foci of the DEN→2-AAF group. F, foci; NF, non-foci.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921921&req=5

fig_005: Comparison of GST-P and Cyp2e1 expression between GST-P foci and the surrounding liver tissue. To ensure all types of GST-P foci will be collected, most of the GST-P-positive foci and surrounding GST-P/Cyp2e1-negative liver tissue in one section are dissected. (A) Western blot analysis of levels of GST-P and Cyp2e1 protein in foci and surrounding tissues (non-foci). (B, C) Semiquantitative analysis of GST-P (B) and Cyp2e1 (C) protein levels in foci and surrounding tissues (non-foci, negative staining for GST-P and Cyp2e1). The levels of GST-P and Cyp2e1 protein were normalized to β-actin. Each bar represents the mean±SD. (n=6). * P<0.05; ** P<0.01 compared with the level of protein in foci of the DEN→2-AAF group. F, foci; NF, non-foci.
Mentions: GST-P-positive foci and the surrounding liver tissue were dissected and collected to detect the levels of GST-P and Cyp2e1 proteins. To ensure all types of GST-P foci will be collected, most of the GST-P-positive foci and surrounding GST-P/Cyp2e1-negative liver tissue in one section are dissected. As shown in Fig. 5Fig. 5.

Bottom Line: By immunohistochemical staining of serial liver sections, we found that the expression of Cyp2e1 in GST-P-positive foci showed three distinct patterns: decreased in GST-P foci, increased in GST-P foci when compared with surrounding liver tissue and mixed type.The number of GST-P foci with increased Cyp2e1 expression was greater than the number of GST-P foci with decreased Cyp2e1.REV or DADS significantly reduced the expression of GST-P and Cyp2e1 in both foci and surrounding liver tissue.

View Article: PubMed Central - PubMed

Affiliation: Center for Drug Safety Evaluation and Research, State Key Laboratory of New Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China.

ABSTRACT
Cyp2e1 plays an important role in chemically induced hepatocarcinogenesis. Resveratrol (REV) is known to prevent diethylnitrosamine (DEN)-induced hepatocarcinogenesis, but its effects on this process induced by DEN and 2-acetylaminofluorene (2-AAF) and the role of Cyp2e1 remain unclear. In this study, glutathione S-transferase placental form (GST-P)-positive foci were used as a marker of hepatocarcinogenesis. REV or diallyl disulfide (DADS, an inhibitor of Cyp2e1) significantly reduced both the area and number of GST-P-positive foci induced by DEN and 2-AAF. Treatment with REV or DADS also markedly decreased the expression of Cyp2e1 in the rat liver. By immunohistochemical staining of serial liver sections, we found that the expression of Cyp2e1 in GST-P-positive foci showed three distinct patterns: decreased in GST-P foci, increased in GST-P foci when compared with surrounding liver tissue and mixed type. The number of GST-P foci with increased Cyp2e1 expression was greater than the number of GST-P foci with decreased Cyp2e1. Protein levels of GST-P and Cyp2e1 were also higher in foci compared with surrounding liver tissue. REV or DADS significantly reduced the expression of GST-P and Cyp2e1 in both foci and surrounding liver tissue. Taken together, these results suggested that REV has a significant inhibitory effect on chemically induced hepatocarcinogenesis, which may be attributed to downregulation of Cyp2e1.

No MeSH data available.


Related in: MedlinePlus