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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

Attenuation of DEN- and 2-AAF-induced hepatocarcinogenesis by REV or DADS. Liver serial sections were used to examine the expression of GST-P and Cyp2e1 by immunohistochemical staining. (A1–D1) Liver sections were stained with GST-P antibody (4×; scale bar, 500 μm); (A2–D2) A high magnification view of the GST-P-positive foci enclosed by a black rectangle in A1–D1 (20×; scale bar, 100 μm); (A3–D3) One serial section of liver stained with Cyp2e1 antibody (4×; scale bar, 500 μm); (A4–D4) a high magnification view of Cyp2e1 enclosed by a black rectangle in A3–D3 (20×; scale bar, 100 μm); (A1–A4) normal untreated liver showing the absence of GST-P foci and low Cyp2e1 expression; (B1–B4) liver sections from the DEN+2-AAF group showing numerous GST-P-positive foci (B1, B2) and extensive staining of Cyp2e1 (B3, B4); (C1–C4) Liver sections from the REV group showing fewer GST-P positive foci (C1, C2) and reduced Cyp2e1 staining compared with the DEN+2-AAF group (C3, C4); (D1–D4) liver sections from the DADS group showing fewer GST-P-positive foci (D1, D2) and reduced Cyp2e1 staining compared with the DEN+2-AAF group (D3, D4). Arrows indicate GST-P-positive foci; arrow heads indicate Cyp2e1 staining.
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fig_003: Attenuation of DEN- and 2-AAF-induced hepatocarcinogenesis by REV or DADS. Liver serial sections were used to examine the expression of GST-P and Cyp2e1 by immunohistochemical staining. (A1–D1) Liver sections were stained with GST-P antibody (4×; scale bar, 500 μm); (A2–D2) A high magnification view of the GST-P-positive foci enclosed by a black rectangle in A1–D1 (20×; scale bar, 100 μm); (A3–D3) One serial section of liver stained with Cyp2e1 antibody (4×; scale bar, 500 μm); (A4–D4) a high magnification view of Cyp2e1 enclosed by a black rectangle in A3–D3 (20×; scale bar, 100 μm); (A1–A4) normal untreated liver showing the absence of GST-P foci and low Cyp2e1 expression; (B1–B4) liver sections from the DEN+2-AAF group showing numerous GST-P-positive foci (B1, B2) and extensive staining of Cyp2e1 (B3, B4); (C1–C4) Liver sections from the REV group showing fewer GST-P positive foci (C1, C2) and reduced Cyp2e1 staining compared with the DEN+2-AAF group (C3, C4); (D1–D4) liver sections from the DADS group showing fewer GST-P-positive foci (D1, D2) and reduced Cyp2e1 staining compared with the DEN+2-AAF group (D3, D4). Arrows indicate GST-P-positive foci; arrow heads indicate Cyp2e1 staining.

Mentions: Immunohistochemical staining of GST-P and Cyp2e1 was performed on serial liver sections. Numerous GST-P-positive foci were found in the liver of the ‘DEN→2-AAF’ group (Fig. 3B1). Treatment with REV or DADS significantly reduced the area and number of GST-P foci (Fig. 3C1 and D1, Fig. 4A-BFig. 4.


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)

Attenuation of DEN- and 2-AAF-induced hepatocarcinogenesis by REV or DADS. Liver serial sections were used to examine the expression of GST-P and Cyp2e1 by immunohistochemical staining. (A1–D1) Liver sections were stained with GST-P antibody (4×; scale bar, 500 μm); (A2–D2) A high magnification view of the GST-P-positive foci enclosed by a black rectangle in A1–D1 (20×; scale bar, 100 μm); (A3–D3) One serial section of liver stained with Cyp2e1 antibody (4×; scale bar, 500 μm); (A4–D4) a high magnification view of Cyp2e1 enclosed by a black rectangle in A3–D3 (20×; scale bar, 100 μm); (A1–A4) normal untreated liver showing the absence of GST-P foci and low Cyp2e1 expression; (B1–B4) liver sections from the DEN+2-AAF group showing numerous GST-P-positive foci (B1, B2) and extensive staining of Cyp2e1 (B3, B4); (C1–C4) Liver sections from the REV group showing fewer GST-P positive foci (C1, C2) and reduced Cyp2e1 staining compared with the DEN+2-AAF group (C3, C4); (D1–D4) liver sections from the DADS group showing fewer GST-P-positive foci (D1, D2) and reduced Cyp2e1 staining compared with the DEN+2-AAF group (D3, D4). Arrows indicate GST-P-positive foci; arrow heads indicate Cyp2e1 staining.
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Related In: Results  -  Collection

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fig_003: Attenuation of DEN- and 2-AAF-induced hepatocarcinogenesis by REV or DADS. Liver serial sections were used to examine the expression of GST-P and Cyp2e1 by immunohistochemical staining. (A1–D1) Liver sections were stained with GST-P antibody (4×; scale bar, 500 μm); (A2–D2) A high magnification view of the GST-P-positive foci enclosed by a black rectangle in A1–D1 (20×; scale bar, 100 μm); (A3–D3) One serial section of liver stained with Cyp2e1 antibody (4×; scale bar, 500 μm); (A4–D4) a high magnification view of Cyp2e1 enclosed by a black rectangle in A3–D3 (20×; scale bar, 100 μm); (A1–A4) normal untreated liver showing the absence of GST-P foci and low Cyp2e1 expression; (B1–B4) liver sections from the DEN+2-AAF group showing numerous GST-P-positive foci (B1, B2) and extensive staining of Cyp2e1 (B3, B4); (C1–C4) Liver sections from the REV group showing fewer GST-P positive foci (C1, C2) and reduced Cyp2e1 staining compared with the DEN+2-AAF group (C3, C4); (D1–D4) liver sections from the DADS group showing fewer GST-P-positive foci (D1, D2) and reduced Cyp2e1 staining compared with the DEN+2-AAF group (D3, D4). Arrows indicate GST-P-positive foci; arrow heads indicate Cyp2e1 staining.
Mentions: Immunohistochemical staining of GST-P and Cyp2e1 was performed on serial liver sections. Numerous GST-P-positive foci were found in the liver of the ‘DEN→2-AAF’ group (Fig. 3B1). Treatment with REV or DADS significantly reduced the area and number of GST-P foci (Fig. 3C1 and D1, Fig. 4A-BFig. 4.

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