Limits...
Protective effect of astaxanthin on liver fibrosis through modulation of TGF-β1 expression and autophagy.

Shen M, Chen K, Lu J, Cheng P, Xu L, Dai W, Wang F, He L, Zhang Y, Chengfen W, Li J, Yang J, Zhu R, Zhang H, Zheng Y, Zhou Y, Guo C - Mediators Inflamm. (2014)

Bottom Line: The same results were confirmed in bile duct liagtion, (BDL) model.These results were simultaneously confirmed in vivo and in vitro.In conclusion, our study showed that 80 mg/kg astaxanthin had a significant protective effect on liver fibrosis by suppressing multiple profibrogenic factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, Shanghai 200072, China.

ABSTRACT
Liver fibrosis is a common pathway leading to cirrhosis and a worldwide clinical issue. Astaxanthin is a red carotenoid pigment with antioxidant, anticancer, and anti-inflammatory properties. The aim of this study was to investigate the effect of astaxanthin on liver fibrosis and its potential protective mechanisms. Liver fibrosis was induced in a mouse model using CCL4 (intraperitoneal injection, three times a week for 8 weeks), and astaxanthin was administered everyday at three doses (20, 40, and 80 mg/kg). Pathological results indicated that astaxanthin significantly improved the pathological lesions of liver fibrosis. The levels of alanine aminotransferase aspartate aminotransferase and hydroxyproline were also significantly decreased by astaxanthin. The same results were confirmed in bile duct liagtion, (BDL) model. In addition, astaxanthin inhibited hepatic stellate cells (HSCs) activation and formation of extracellular matrix (ECM) by decreasing the expression of NF-κB and TGF-β1 and maintaining the balance between MMP2 and TIMP1. In addition, astaxanthin reduced energy production in HSCs by downregulating the level of autophagy. These results were simultaneously confirmed in vivo and in vitro. In conclusion, our study showed that 80 mg/kg astaxanthin had a significant protective effect on liver fibrosis by suppressing multiple profibrogenic factors.

Show MeSH

Related in: MedlinePlus

Effect of astaxanthin on CCL4-induced liver fibrosis. (a) Astaxanthin decreased the level of ALT, AST, and hydroxyproline with the doses of 40 mg/kg and 80 mg/kg. Data are expressed as mean ± SD (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4). (b) Astaxanthin (40 mg/kg and 80 mg/kg) ameliorated pathological change showed by H&E, Masson's trichrome (MT), and sirius red staining (original magnification: ×200). (c) The areas of positive staining with MT and SR were analyzed by Image-pro Plus 6.0. There existed a significant decrease with astaxanthin (40 mg/kg and 80 mg/kg) treatment (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4).
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4016904&req=5

fig1: Effect of astaxanthin on CCL4-induced liver fibrosis. (a) Astaxanthin decreased the level of ALT, AST, and hydroxyproline with the doses of 40 mg/kg and 80 mg/kg. Data are expressed as mean ± SD (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4). (b) Astaxanthin (40 mg/kg and 80 mg/kg) ameliorated pathological change showed by H&E, Masson's trichrome (MT), and sirius red staining (original magnification: ×200). (c) The areas of positive staining with MT and SR were analyzed by Image-pro Plus 6.0. There existed a significant decrease with astaxanthin (40 mg/kg and 80 mg/kg) treatment (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4).

Mentions: To examine the effect of astaxanthin on liver fibrosis, we first determined ALT and AST levels in serum. A significant increase in both ALT and AST was observed in the CCL4-treated group compared to the control group. Serum levels of ALT and AST decreased significantly after astaxanthin treatment (40 mg/kg and 80 mg/kg). However, 20 mg/kg of astaxanthin had no effect (Figure 1(a)). Liver sections were stained with H&E to evaluate liver injury. Severe liver injury and fibrosis were observed in the CCL4-treated group, with necrosis of hepatocytes, damage to liver lobules, and pericellular bridging fibrosis. These changes were markedly reduced in liver sections from the astaxanthin-treated group (40 mg/kg and 80 mg/kg) (Figure 1(b)). Fibrosis is the foremost characteristic of chronic liver injury, with collagen deposits seen in fibrotic tissue. Therefore, we determined the level of hydroxyproline in liver tissue, which reflects total collagen content. Astaxanthin at 40 mg/kg and 80 mg/kg decreased the level of hydroxyproline (Figure 1(a)). We used Masson's trichrome (MT) and sinus red (SR) to stain collagen. Both of these histopathological analyses revealed increased collagen around the portal triad, the lobules were surrounded by bundles of collagen fibers, normal structure was lost, and large fibrous septa were present in the CCL4-treated group (Figure 1(b)). Consistent with ALT and AST analyses and H&E staining, the area and thickness of collagen fiber bundles (stained blue and red, respectively) were decreased following administration of astaxanthin (40 mg/kg and 80 mg/kg). A statistically significant difference in MT and SR-staining was noted between astaxanthin-treated group (40 mg/kg and 80 mg/kg) and CCL4 group, when the staining intensity was analyzed with the software named Image-Pro Plus 6.0 (Figure 1(c)). In addition, astaxanthin (80 mg/kg) was also administrated in BDL model, and results showed that the fibrosis in BDL model was significantly ameliorated by astaxanthin (80 mg/kg) (Figure 2). These results indicated that astaxanthin ameliorated liver fibrosis.


Protective effect of astaxanthin on liver fibrosis through modulation of TGF-β1 expression and autophagy.

Shen M, Chen K, Lu J, Cheng P, Xu L, Dai W, Wang F, He L, Zhang Y, Chengfen W, Li J, Yang J, Zhu R, Zhang H, Zheng Y, Zhou Y, Guo C - Mediators Inflamm. (2014)

Effect of astaxanthin on CCL4-induced liver fibrosis. (a) Astaxanthin decreased the level of ALT, AST, and hydroxyproline with the doses of 40 mg/kg and 80 mg/kg. Data are expressed as mean ± SD (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4). (b) Astaxanthin (40 mg/kg and 80 mg/kg) ameliorated pathological change showed by H&E, Masson's trichrome (MT), and sirius red staining (original magnification: ×200). (c) The areas of positive staining with MT and SR were analyzed by Image-pro Plus 6.0. There existed a significant decrease with astaxanthin (40 mg/kg and 80 mg/kg) treatment (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4016904&req=5

fig1: Effect of astaxanthin on CCL4-induced liver fibrosis. (a) Astaxanthin decreased the level of ALT, AST, and hydroxyproline with the doses of 40 mg/kg and 80 mg/kg. Data are expressed as mean ± SD (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4). (b) Astaxanthin (40 mg/kg and 80 mg/kg) ameliorated pathological change showed by H&E, Masson's trichrome (MT), and sirius red staining (original magnification: ×200). (c) The areas of positive staining with MT and SR were analyzed by Image-pro Plus 6.0. There existed a significant decrease with astaxanthin (40 mg/kg and 80 mg/kg) treatment (n = 7, *P < 0.05 for CCL4 + AST(40) versus CCL4, #P < 0.05 for CCL4 + AST(80) versus CCL4).
Mentions: To examine the effect of astaxanthin on liver fibrosis, we first determined ALT and AST levels in serum. A significant increase in both ALT and AST was observed in the CCL4-treated group compared to the control group. Serum levels of ALT and AST decreased significantly after astaxanthin treatment (40 mg/kg and 80 mg/kg). However, 20 mg/kg of astaxanthin had no effect (Figure 1(a)). Liver sections were stained with H&E to evaluate liver injury. Severe liver injury and fibrosis were observed in the CCL4-treated group, with necrosis of hepatocytes, damage to liver lobules, and pericellular bridging fibrosis. These changes were markedly reduced in liver sections from the astaxanthin-treated group (40 mg/kg and 80 mg/kg) (Figure 1(b)). Fibrosis is the foremost characteristic of chronic liver injury, with collagen deposits seen in fibrotic tissue. Therefore, we determined the level of hydroxyproline in liver tissue, which reflects total collagen content. Astaxanthin at 40 mg/kg and 80 mg/kg decreased the level of hydroxyproline (Figure 1(a)). We used Masson's trichrome (MT) and sinus red (SR) to stain collagen. Both of these histopathological analyses revealed increased collagen around the portal triad, the lobules were surrounded by bundles of collagen fibers, normal structure was lost, and large fibrous septa were present in the CCL4-treated group (Figure 1(b)). Consistent with ALT and AST analyses and H&E staining, the area and thickness of collagen fiber bundles (stained blue and red, respectively) were decreased following administration of astaxanthin (40 mg/kg and 80 mg/kg). A statistically significant difference in MT and SR-staining was noted between astaxanthin-treated group (40 mg/kg and 80 mg/kg) and CCL4 group, when the staining intensity was analyzed with the software named Image-Pro Plus 6.0 (Figure 1(c)). In addition, astaxanthin (80 mg/kg) was also administrated in BDL model, and results showed that the fibrosis in BDL model was significantly ameliorated by astaxanthin (80 mg/kg) (Figure 2). These results indicated that astaxanthin ameliorated liver fibrosis.

Bottom Line: The same results were confirmed in bile duct liagtion, (BDL) model.These results were simultaneously confirmed in vivo and in vitro.In conclusion, our study showed that 80 mg/kg astaxanthin had a significant protective effect on liver fibrosis by suppressing multiple profibrogenic factors.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, Shanghai 200072, China.

ABSTRACT
Liver fibrosis is a common pathway leading to cirrhosis and a worldwide clinical issue. Astaxanthin is a red carotenoid pigment with antioxidant, anticancer, and anti-inflammatory properties. The aim of this study was to investigate the effect of astaxanthin on liver fibrosis and its potential protective mechanisms. Liver fibrosis was induced in a mouse model using CCL4 (intraperitoneal injection, three times a week for 8 weeks), and astaxanthin was administered everyday at three doses (20, 40, and 80 mg/kg). Pathological results indicated that astaxanthin significantly improved the pathological lesions of liver fibrosis. The levels of alanine aminotransferase aspartate aminotransferase and hydroxyproline were also significantly decreased by astaxanthin. The same results were confirmed in bile duct liagtion, (BDL) model. In addition, astaxanthin inhibited hepatic stellate cells (HSCs) activation and formation of extracellular matrix (ECM) by decreasing the expression of NF-κB and TGF-β1 and maintaining the balance between MMP2 and TIMP1. In addition, astaxanthin reduced energy production in HSCs by downregulating the level of autophagy. These results were simultaneously confirmed in vivo and in vitro. In conclusion, our study showed that 80 mg/kg astaxanthin had a significant protective effect on liver fibrosis by suppressing multiple profibrogenic factors.

Show MeSH
Related in: MedlinePlus