• Toxicological Research
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• v.26 no.3
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• pp.193-201
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• 2010

Hepatic fibrosis represents the main complication of most chronic liver disorders and, regardless of its etiology, is characterized by excessive deposition of extracellular matrix components. In this study, we examined that 1-O-Hexyl-2,3,5-Trimethylhydroquinone (HTHQ), a potent anti-oxidative agent, could prevent experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in male SD rats. Except for vehicle control group, other groups were induced hepatic fibrosis by intraperitoneal injection with DMN (10 mg/ml/kg) on 3 consecutive days weekly for 4 weeks. During the same 4 weeks, control and DMN groups were given vehicle and HTHQ 50, 100 and 200 groups were orally administered HTHQ (50, 100, 200 mg/kg respectively). In HTHQ 100 and 200 groups, relative liver weight and serum chemistry level improved significantly. HTHQ reduced hydroxyproline (p < 0.05) and malondialdehyde (p < 0.05) level in the liver. Histopathological examination of H&E, Masson's trichrome stain showed the reduced fibrotic septa in HTHQ 100 and 200 groups. HTHQ administration showed reduced mRNA level of PDGF (Platelet-derived growth factor), $\alpha$-SMA ($\alpha$-smooth muscle actin) and TGF-$\beta$ (transforming growth factor-$\beta$) than DMN-induced hepetic fibrosis animals in the liver tissue. In this study, we showed that HTHQ improves against DMN-induced liver fibrosis in male SD rats.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.172.2-173
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• 2003

Naringenin, a phytoalexin found in grapefruit. has been reported to exhibit a wide range of pharmacological properties. The aim of the present study is to evaluate the protective effect of naringenin on hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Fibrosis was induced by intraperitoneal injection of DMN. Naringenin was given orally at 20 mg/kg and 50 mg/kg daily for 4 weeks. (omitted)

• Journal of the East Asian Society of Dietary Life
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• v.23 no.1
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• pp.44-52
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• 2013

This study investigated hepatic functional improvement and anti-fibrotic effects of water extracts of black tea. Male Sprague-Dawley rats were divided into four groups (normal, control, and two experimental subgroups: Ba, Bb) and observed for 3 weeks. Liver fibrosis in rats developed from carbon tetrachloride ($CCl_4$) administration, except for the normal group. Except for the normal and control group, the two experimental subgroups were fed water extracts of black tea. The food efficiency ratio significantly increased in the experimental group compared to the control group. The experimental group had a significantly lower liver weight compared to the control group. The ratio of liver weight to body weight was significantly lower in the experimental group than the control group. The levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, and low-density lipoprotein-cholesterol in serum significantly decreased in the experimental group compared to the control group. The values of hydroxyproline and malondialdehyde in liver were even lower in the experimental group than the control group. In observations on liver histology, weaker inflammation and fibrosis were observed in the experimental group compared to the control group. In conclusion, water extracts of black tea help hepatic cells keep their functions, restraining and protecting the liver from impairments caused by $CCl_4$ administration, and can be effective as anti-fibrotic agents.

• Journal of Applied Biological Chemistry
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• v.59 no.1
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• pp.25-29
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• 2016

Hepatitis B virus infection can cause hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma. However the mechanism remains poorly understood. In this study, we found that Hepatitis B virus X-protein (HBx) increases vimentin, fibronectin, slug, snail and NOX4 expression. Because NOX4-mediated reactive oxygen species can increase slug and snail, which can induce fibrosis, HBx may be a key regulator of hepatic fibrosis development via NOX4 induction.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.5
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• pp.1264-1269
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• 2003

The inhibitory effects of the Juglans sinensis walnut ethanol extract (JSWE) on carbon tetrachloide (CCl₄)-induced fibrosis, serum transaminases (GOT and GTP), hepatic glutathione (GSH), serum pro-inflammatory cytokines (IL-1β and IL-6) were investigated in rats. JSWE significantly inhibited on CCl₄-induced fibrosis in dose-dependent manner. Moreover, JSWE significantly inhibited on the serum levels of GOT, GTP, IL-1β, and IL-6 in dose-dependent manner in CCl₄-induced fibrosis rat. However, JSWE markedly increased the production of hepatic GSH in a dose-dependent manner. These results show that JSWE may explain some known biological activities of Juglans sinensis walnut including their anti-fibrotic and anti-inflammatory effects, and is of considerable benefit in the treatment for live diseases.

• Biomolecules & Therapeutics
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• v.28 no.1
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• pp.92-97
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• 2020

A previous pharmacogenomic analysis identified cromolyn, an anti-allergic drug, as an effective anti-fibrotic agent that acts on hepatocytes and stellate cells. Furthermore, cromolyn was shown to be a G protein-coupled receptor 35 (GPR35) agonist. However, it has not been studied whether anti-fibrotic effects are mediated by GPR35. Therefore, in this study, the role of GPR35 in hepatic fibrosis was investigated through the use of lodoxamide, another anti-allergic drug and a potent GPR35 agonist. Long-term treatment with carbon tetrachloride induced hepatic fibrosis, which was inhibited by treatment with lodoxamide. Furthermore, CID2745687, a specific GPR35 antagonist, reversed lodoxamide-mediated anti-fibrotic effects. In addition, lodoxamide treatment showed significant effects on the mRNA expression of collagen Iα1, collagen Iα2, and TGF-β1 in the extracellular matrix. However, a transforming growth factor α (TGF-α) shedding assay revealed lodoxamide not to be a potent agonist of mouse GPR35 in vitro. Therefore, these results showed anti-fibrotic effects of lodoxamide in mice and raise concerns how lodoxamide protects against liver fibrosis in vivo and whether GPR35 is involved in the action.

• Clinical and Experimental Pediatrics
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• v.45 no.7
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• pp.923-927
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• 2002

Congenital hepatic fibrosis is a relatively rare disease, characterized by bile ductular proliferation and prominent fibrosis in the portal area of liver resulting in portal hypertension. It is frequently associated with other abnormalities such as polycystic kidney, Caroli syndrome, cystic dysplasia of pancreas, intestinal lymphangiectasia, pulmonary emphysema, hemangioma, and cleft palate. We report here a case of congenital hepatic fibrosis associated with renal tubular ectasia in a 3-year-old girl, whose chief complaint was abdominal distension. Her liver function test did not reveal any abnormal findings. Hepatosplenomegaly and multiple dilated bile ducts were seen in the abdominal CT scaning. Esophageal varix was not detected by an endoscopic examination. Microscopically, diffuse portal fibrosis and widening with proliferation of blie ductules in the liver specimen and tubular ectasia in renal cortex were seen.

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2003.10a
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• pp.16-16
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• 2003

Hepatic fibrosis is a common response to various chronic hepatic injuries and occurs as a consequence of the transformation of hepatic stellate cells into myofibroblasts (MFBs) producing abnormal extracellular matrix which is mainly induced by transforming growth factor-beta (TGF-${\beta}$), especially TGF-${\beta}$1 [1,2]. As the liver becomes fibrotic, there are both quantitative and qualitative changes in several pathological markers related to the hepatic fibrosis. These fibrotic markers in liver are mainly consisted of several proteins and cytokines, but sometimes included specific type cells. The aim of this study was to detect expression and change of markers (TGF-${\beta}$, mallory body, cytokeratin, ${\alpha}$-SMA, hypoxia, collagen) during hepatic fibrogenesis. (omitted)

• The Journal of Internal Korean Medicine
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• v.32 no.4
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• pp.504-518
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• 2011

Objectives : This study was performed to investigate the anti-fibrogenic effect of greater celandine on cultured rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells (HSC-T6) were treated with various concentrations of greater celandine extract for 24, 48, and 72 hours. The extraction was done with distilled water. After the treatment, cell viability, proliferation, mRNA of the ${\alpha}SMA$, TIMP-1, TIMP-2, collagen I ${\alpha}$ 1, MMP-2, IL-6, TGF-${\beta}1$, PDGFr-${\beta}1$, Bcl-2, Bax, Bcl-xl, caspase-3, caspase-9 and the activities of SOD and catalase were measured by using MTT assay, BrdU assay, real-time PCR, superoxide dismutase assay and catalase assay. Results : The viability, proliferation, mRNA expression and synthesis of collagen of the hepatic stellate cells were inhibited as the concentration increased, which indicates the herb has an inhibitory effect on fibrogenesis of the liver by regulating the fibrosis associated genes in transcription. Conclusions : These results suggest that greater celandine would be beneficial in the treatment of fibrotic patients as well as for patients with chronic hepatitis.

• Nutrition Research and Practice
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• v.4 no.5
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• pp.369-374
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• 2010

Grape is one of the most popular and widely cultivated fruits in the world. Although grape skin and seeds are waste product of the winery and grape juice industry, these wastes contain large amounts of phytochemicals such as flavonoids, phenolic acids, and anthocyanidins, which play an important role as chemopreventive and anticancer agents. We evaluated efficacies of grape skin and seeds on hepatic injury induced by dimethylnitrosamine (DMN) in rats. Treatment with DMN significantly increased levels of serum alanine transaminase, aspartate transaminase, alkaline phosphatase, and bilirubin. Diet supplementation with grape skin or seeds (10% daily for 4 weeks) prevented these elevations. The grape skin and seeds also restored serum albumin and total protein levels, and reduced the hepatic level of hydroxyproline and malondialdehyde. Furthermore, grape skin and seeds reduced DMN-induced collagen accumulation, as estimated by histological analysis of liver tissue stained with Sirius red. Grape skin and seeds also reduced hepatic stellate cell activation, as assessed by ${\alpha}$-smooth muscle actin staining. In conclusion, grape skin and seeds exhibited in vivo hepatoprotective and antifibrogenic effects against DMN-induced liver injury, suggesting that grape skin and seeds may be useful in preventing the development of hepatic fibrosis.