Value of Fibrosis Markers for Staging Liver Fibrosis in Patients With Precirrhotic Alcoholic Liver Disease

Lieber, Charles S.; Weiss, David G.; Paronetto, Fiorenzo

doi:10.1111/j.1530-0277.2008.00664.x

Cited by 57 publications

(52 citation statements)

References 47 publications

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“…CCl 4 has been widely used to induce chronic liver damage, especially in models of hepatic fibrosis and primary hepatic cirrhosis [39] . ROS play an important role in the activation of HSC and collagen accumulation in alcohol-related hepatic fibrosis [38,[40][41][42][43][44] . It is now generally accepted that liver fibrosis produced by CCl 4 is induced by oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis

Gao

Chu

et al. 2014

Acta Pharmacol Sin

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Aim: To investigate the anti-fibrosis effects of ginsenoside Rg1 on alcohol-and CCl 4 -induced hepatic fibrosis in rats and to explore the mechanisms of the effects. Methods: Rats were given 6% alcohol in water and injected with CCl 4 (2 mL/kg, sc) twice a week for 8 weeks. Rg1 (10, 20 and 40 mg/kg per day, po) was administered in the last 2 weeks. Hepatic fibrosis was determined by measuring serum biochemical parameters, HE staining, Masson's trichromic staining, and hydroxyproline and α-SMA immunohistochemical staining of liver tissues. The activities of antioxidant enzymes, lipid peroxidation, and Nrf2 signaling pathway-related proteins (Nrf2, Ho-1 and Nqo1) in liver tissues were analyzed. Cultured hepatic stellate cells (HSCs) of rats were prepared for in vitro studies. Results: In the alcohol-and CCl 4 -treated rats, Rg1 administration dose-dependently suppressed the marked increases of serum ALT, AST, LDH and ALP levels, inhibited liver inflammation and HSC activation and reduced liver fibrosis scores. Rg1 significantly increased the activities of antioxidant enzymes (SOD, GSH-Px and CAT) and reduced MDA levels in liver tissues. Furthermore, Rg1 significantly increased the expression and nuclear translocation of Nrf2 that regulated the expression of many antioxidant enzymes. Treatment of the cultured HSCs with Rg1 (1 μmol/L) induced Nrf2 translocation, and suppressed CCl 4 -induced cell proliferation, reversed CCl 4-induced changes in MDA, GPX, PCIII and HA contents in the supernatant fluid and α-SMA expression in the cells. Knockdown of Nrf2 gene diminished these actions of Rg1 in CCl 4 -treated HSCs in vitro. Conclusion: Rg1 exerts protective effects in a rat model of alcohol-and CCl 4 -induced hepatic fibrosis via promoting the nuclear translocation of Nrf2 and expression of antioxidant enzymes.

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Section: Discussionmentioning

confidence: 99%

Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis

Gao

Chu

et al. 2014

Acta Pharmacol Sin

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“…Of special interest was correction of collagens 1, 3, and 4, tissue inhibitor of metalloproteinase 1 (Timp) and vinculin (Vcl), well-known markers of fibrosis. 27,28 Picro-sirius red staining indeed showed slightly increased deposition of fibrillar collagens in the centrilobular area of ob/ob livers. Treatment of ob/ob mice with AMP-DNM largely normalized this pattern to that of control lean mice (data not shown).…”

Section: Amp-dnm Reduces Hepatic Markers Associated With Matrix Remodmentioning

confidence: 99%

Modulation of glycosphingolipid metabolism significantly improves hepatic insulin sensitivity and reverses hepatic steatosis in mice

et al. 2009

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Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and type 2 diabetes. The hyperinsulinemia that occurs as a consequence of insulin resistance is thought to be an important contributor to the development of fatty liver. We have shown that the iminosugar N-(5'-adamantane-1'-yl-methoxy)-pentyl-1-deoxynojirimycin (AMP-DNM), an inhibitor of the enzyme glucosylceramide synthase, is a potent enhancer of insulin signaling in rodent models for insulin resistance and type 2 diabetes. The present study was designed to assess the impact of AMP-DNM on insulin levels, liver triglyceride synthesis, and gene expression profile. Treatment of ob/ob mice with AMP-DNM restored insulin signaling in the liver, corrected blood glucose values to levels found in lean mice, and decreased insulin concentration. The expression of sterol regulatory element-binding protein 1c target genes involved in fatty acid synthesis normalized. AMP-DNM treatment significantly reduced liver to body weight ratio and reversed hepatic steatosis, comprising fat as well as inflammatory markers. In addition, AMP-DNM treatment corrected to a large extent the gene expression profile of ob/ob mice livers toward the profile of lean mice. Conclusion: Pharmacological lowering of glycosphingolipids with the iminosugar AMP-DNM is a promising approach to restore insulin signaling and improve glucose homeostasis as well as hepatic steatosis.

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“…Indeed over the last years good antibodies have been generated that allow detection of tenascin-C expression by immunohistochemistry. Tissue staining is already applied in assessment of cancer and other diseases with high expression of tenascin-C such as fibrosis 5,6 and inflammation in myocarditis. 7 Tenascin-C is also found in body fluids such as blood and milk.…”

Section: Exploiting High Tenascin-c Expression In Cancer For Diagnosimentioning

confidence: 99%

Tenascin-C: Exploitation and collateral damage in cancer management

Spenlé

Saupe

Midwood³

et al. 2015

Cell Adhesion & Migration

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Value of Fibrosis Markers for Staging Liver Fibrosis in Patients With Precirrhotic Alcoholic Liver Disease

Cited by 57 publications

References 47 publications

Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis

Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis

Modulation of glycosphingolipid metabolism significantly improves hepatic insulin sensitivity and reverses hepatic steatosis in mice

Tenascin-C: Exploitation and collateral damage in cancer management

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