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Vitamin A supplementation alleviates extrahepatic cholestasis liver injury through Nrf2 activation.

Wang G, Xiu P, Li F, Xin C, Li K - Oxid Med Cell Longev (2014)

Bottom Line: Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice.Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1.Vitamin A was here found to ameliorate cholestatic liver injury.

View Article: PubMed Central - PubMed

Affiliation: Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

ABSTRACT

Aim: To investigate the role of vitamin A in liver damage induced by bile duct ligation (BDL) in rats.

Methods: Thirty male Wistar rats were randomly divided into three groups: SHAM group, BDL group, and BDL + VitA group . The concentrations of retinol and retinyl palmitate in the liver were analyzed using HPLC, and liver function was evaluated by the level of TBIL, ALT, AST, and ALP in serum. Hepatic oxidative status was estimated by measuring T-SOD, CAT, GSH, MDA, and AOPP. Nrf2 expression was assessed using immunohistochemistry and western blotting, and EMSA was performed to determine Nrf2 DNA-binding activity. The expression of the downstream factors such as Ho1 and Nqo1 was also examined using immunohistochemistry and western blotting assays.

Results: Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice. Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1.

Conclusion: Vitamin A was here found to ameliorate cholestatic liver injury. This effect may be related to the activation of Nrf2/ARE pathway in bile duct ligation rats.

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Related in: MedlinePlus

Immunohistochemical staining of liver Nrf2 expression (original magnification: ×400; arrows indicate nucleus-positive cells). More Nrf2 was concentrated in the nuclei of the BDL group than in the SHAM group, and this concentration morphology was more apparent after treatment with vitamin A.
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fig5: Immunohistochemical staining of liver Nrf2 expression (original magnification: ×400; arrows indicate nucleus-positive cells). More Nrf2 was concentrated in the nuclei of the BDL group than in the SHAM group, and this concentration morphology was more apparent after treatment with vitamin A.

Mentions: Immunohistochemical staining and western blotting assays showed that vitamin A led to Nrf2 accumulation in nucleus in BDL rats treated with vitamin A after 2 weeks (Figure 5 and Figure 6(a)). Statistical analysis also showed there is a significant difference between Nrf2 levels in cytoplasm of the three groups (P < 0.05). EMSA showed Nrf2-ARE-binding activity has been enhanced after BDL and substantially increased after treatment with vitamin A (Figure 6(b)). The expression of antioxidative proteins Ho1 and Nqo1 downstream of Nrf2 was also examined. Immunohistochemistry and western blot results indicated that both Ho1 and Nqo1 proteins were upregulated after BDL (P < 0.05, Figures 7, 8, and 9). Additionally, administration of vitamin A for 2 weeks further increased the expression of protein overexpression in the BDL group (P < 0.05, Figures 7–9).


Vitamin A supplementation alleviates extrahepatic cholestasis liver injury through Nrf2 activation.

Wang G, Xiu P, Li F, Xin C, Li K - Oxid Med Cell Longev (2014)

Immunohistochemical staining of liver Nrf2 expression (original magnification: ×400; arrows indicate nucleus-positive cells). More Nrf2 was concentrated in the nuclei of the BDL group than in the SHAM group, and this concentration morphology was more apparent after treatment with vitamin A.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4120926&req=5

fig5: Immunohistochemical staining of liver Nrf2 expression (original magnification: ×400; arrows indicate nucleus-positive cells). More Nrf2 was concentrated in the nuclei of the BDL group than in the SHAM group, and this concentration morphology was more apparent after treatment with vitamin A.
Mentions: Immunohistochemical staining and western blotting assays showed that vitamin A led to Nrf2 accumulation in nucleus in BDL rats treated with vitamin A after 2 weeks (Figure 5 and Figure 6(a)). Statistical analysis also showed there is a significant difference between Nrf2 levels in cytoplasm of the three groups (P < 0.05). EMSA showed Nrf2-ARE-binding activity has been enhanced after BDL and substantially increased after treatment with vitamin A (Figure 6(b)). The expression of antioxidative proteins Ho1 and Nqo1 downstream of Nrf2 was also examined. Immunohistochemistry and western blot results indicated that both Ho1 and Nqo1 proteins were upregulated after BDL (P < 0.05, Figures 7, 8, and 9). Additionally, administration of vitamin A for 2 weeks further increased the expression of protein overexpression in the BDL group (P < 0.05, Figures 7–9).

Bottom Line: Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice.Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1.Vitamin A was here found to ameliorate cholestatic liver injury.

View Article: PubMed Central - PubMed

Affiliation: Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

ABSTRACT

Aim: To investigate the role of vitamin A in liver damage induced by bile duct ligation (BDL) in rats.

Methods: Thirty male Wistar rats were randomly divided into three groups: SHAM group, BDL group, and BDL + VitA group . The concentrations of retinol and retinyl palmitate in the liver were analyzed using HPLC, and liver function was evaluated by the level of TBIL, ALT, AST, and ALP in serum. Hepatic oxidative status was estimated by measuring T-SOD, CAT, GSH, MDA, and AOPP. Nrf2 expression was assessed using immunohistochemistry and western blotting, and EMSA was performed to determine Nrf2 DNA-binding activity. The expression of the downstream factors such as Ho1 and Nqo1 was also examined using immunohistochemistry and western blotting assays.

Results: Vitamin A treatment restored levels of retinoids in liver, improved liver function, alleviated oxidative stress, and facilitated the translocation of Nrf2 to the nucleus in the experimental obstructive jaundice. Vitamin A was also found to increase the expression of Nrf2 downstream proteins such as Ho1 and Nqo1.

Conclusion: Vitamin A was here found to ameliorate cholestatic liver injury. This effect may be related to the activation of Nrf2/ARE pathway in bile duct ligation rats.

Show MeSH
Related in: MedlinePlus