Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0239946 (liver fibrosis)
 8,268 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Overexpression of transforming growth factor beta 1 (TGF beta 1) and increased transcription of pro-collagen type I, are known to represent major events implicated in the development of liver fibrosis under either experimental or clinical conditions. Here we report that long-term dietary vitamin E supplementation in animals undergoing an experimental model of liver fibrosis (induced by chronic treatment of rats with carbon tetrachloride) results in a net inhibition of both hepatic TGF beta 1 and alpha 2 (I) procollagen mRNA levels. Moreover, of striking interest is the observation that vitamin E supplementation per so down-modulates basal levels of TGF beta 1 mRNA in the liver of untreated animals, suggesting that a dietary regimen rich in vitamin E may potentially interfere with both the initiation and progression of the fibrosclerotic processes.
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PMID:Vitamin E dietary supplementation inhibits transforming growth factor beta 1 gene expression in the rat liver. 150 65

Experimental evidence indicates that the lipid peroxidation of biological membranes is often associated with the development of liver fibrosis. We have studied the effect of neutrophil-derived reactive oxygen species (ROS) on collagen synthesis by human hepatic stellate cells (HSC), the major source of collagen in the liver, in a coculture system. Lipid peroxidation in the cocultures was evaluated in terms of either malondialdehyde (MDA) production or the formation of MDA/4-hydroxynonenal protein adducts. The expression of cellular messenger RNAs (mRNAs) was evaluated by either Northern blotting or RNAse protection assay. Nitric oxide (NO) synthase activity in cells was measured by [3H]citrulline formation from [3H]arginine. In vitro exposure of HSC to ROS resulted in the early induction of lipid peroxidation and was associated with a marked increase (threefold) of procollagen I mRNA expression and synthesis. The addition of antioxidants, such as vitamin E or superoxide dismutase (SOD), impaired this stimulation. The inhibition of neutrophil NO formation by N(G)-monomethyl-L-arginine made the ROS-induced stimulation of procollagen I more evident. The addition of xanthine/xanthine oxidase X/XO, a superoxide anion donor, to HSC cultures strongly increased procollagen I synthesis. This stimulation was hampered by the addition of both SOD and sodium nitroprusside (an NO donor). The contribution of HSC to the production of NO in our coculture system was negligible, because inducible NO synthase (iNOS) mRNA was almost undetectable in these cells, and also because the amount of NO produced by HSC stimulated with tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide (LPS) was 500 times less than that synthesized by neutrophils. In conclusion, these results indicate that neutrophil-derived ROS may contribute to the development of hepatic fibrosis associated with alcoholic hepatitis. NO produced by neutrophils may exert a "protective" antioxidant effect by operating as a scavenger of superoxide anion.
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PMID:Neutrophil-derived superoxide anion induces lipid peroxidation and stimulates collagen synthesis in human hepatic stellate cells: role of nitric oxide. 902 48

Recent studies demonstrated the role of antioxidants in preventing organ damage caused by free radicals. The present study was conducted to find out the modulatory effect of some antioxidants on lipid patterns in experimentally-induced liver damage. Rats chronically intoxicated with carbon tetrachloride (CCl4) were used as a model of liver injury terminating with fibrosis or cirrhosis. One hundred and sixty six albino rats were classified into five groups: one served as a control group; the second was subjected to oral administration of CCl4 (200 microL/100 g body weight) twice a week; the other three groups, in addition to CCl4, received oral doses of silymarin (30 mg/kg), vitamin E (200 IU/kg) and vitamin C (50 mg/kg) respectively. At the end of the experiment, the animals were killed, blood was collected and liver was taken for histopathological examination. Liver function tests, disturbed by CCl4 were significantly modulated by antioxidants, and histopathological examination showed that antioxidants ameliorated the necrotic and fibrotic changes caused by CCl4. Treatment with antioxidants was also shown to modulate the toxic effect of CCl4 on the lipid profile and malondialdehyde content. Administration of antioxidants could play an important role in prophylaxis against lipid peroxidation and consequently liver fibrosis caused by free radicals.
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PMID:Biochemical effect of antioxidants on lipids and liver function in experimentally-induced liver damage. 936 4

This experiment was carried out to investigate the role of antioxidants such as vitamin C and E, selenium and Nigella sativa (NS) on the prevention of carbon tetrachloride (CCl4)-induced liver fibrosis in rabbits. It was found that superoxide dismutase (SOD) values in all of the treated groups were significantly lower than those of the control at 12th week of experiment (p < 0.05), while at 6th week and 12th week of experiment glutathione peroxidase (GSH-Px) values in the vitamin C treated group were significantly different from the control (p < 0.05). Histopathologically, hepatocellular necrosis, degeneration and advanced fibrosis were found in the control group. Lesions were minor and only confined to midzonal regions without centrilobular necrosis and fibrosis in the NS treated animals (group B). The lesions observed in the vitamin C treated animals (group C) were similar to that of the control group. Parenchymal changes with fibrosis were less in selenium and vitamin E treated animals (group D) than in those of the control group, but more obvious than in NS group. Histopathological findings demonstrate that NS might, at least partly, be successful in the prevention of liver fibrosis in rabbits. Vitamin E plus selenium had little therapeutic effect and vitamin C seemed to be ineffective, as far as the results of this study are concerned.
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PMID:The role of antioxidant vitamins (C and E), selenium and Nigella sativa in the prevention of liver fibrosis and cirrhosis in rabbits: new hopes. 1136 85

Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver injury ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. Whereas simple steatosis has a benign clinical course, steatohepatitis is a recognized cause of progressive liver fibrosis and can develop into cirrhosis. NAFLD and nonalcoholic steatohepatitis (NASH) are the two most common chronic liver diseases in United States general population with a prevalence of 20% and 3%, respectively. Hepatic steatosis is frequently associated with obesity, type 2 diabetes, and hyperlipidemia with insulin resistance as a key pathogenic factor. A two-hit theory best describes the progression from simple steatosis to NASH, fibrosis, or cirrhosis. These two hits consist of the accumulation of excessive hepatic fat primarily owing to insulin resistance, and oxidative stress owing to reactive oxygen species (ROS). Mitochondria are the major cellular source of ROS in cases of NASH. Currently, treatment is focused on modifying risk factors such as obesity, diabetes mellitus, and hyperlipidemia. Antioxidants such as vitamin E, N-acetylcysteine, betaine, and others may be beneficial in the treatment of NASH.
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PMID:Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants. 1229 56

Nonalcoholic steatohepatitis (NASH) occurs not only in adults but also in children. NASH is diagnosed in obese children with increased aminotranspherases, characteristic ultrasonography and typical percutneous liver biopsy (fat vacuoles in hepatocytes, different stages of inflammation with or without liver fibrosis) when other possible causes of steatosis are excluded. It is important to diagnose NASH and start the treatment as early as possible in order to prevent irreversible liver damage. The first line therapy consists of reduction of body weight by low-calorie diet and exercising. Ursodeoxycholic acid has been used as adjuvant therapy mainly in adults, and vitamin E also in children. We presented 5 cases with NASH (2 girls, 3 boys; age 11-15 years). All were obese and had increased transaminases, and ultrasonography and liver biopsy typical for NASH. With low-calorie diet in all our patients BMI declined, symptoms vanished and transaminases decreased (in two patients transaminases normalized).
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PMID:[Nonalcoholic steatohepatitis in children]. 1575 89

Nonalcoholic fatty liver disease (NAFLD) is becoming an increasing cause of chronic liver damage. The decision of start a medical treatment is based on the documented risk of progression to cirrhosis and liver cancer, when steatohepatitis (NASH) occurs. The therapy of this syndrome requires, as obviously, some considerations on the natural history of the condition, on the efficacy and safety of various therapeutic options, as well as on the costs. Treatment of patients with NAFLD has typically been focused on the management of associated conditions such as obesity, diabetes mellitus and hyperlipemia. Weight loss improves insulin sensitivity, and NASH may resolve with weight reduction. Insulin resistance seems to be the common denominator in many cases of NAFLD. Two classes of drugs have been shown to correct insulin resistance: biguanides (e.g., metformin) and thiazolidinediones (e.g., rosiglitazone and pioglitazone). The last two decades have witnessed a considerable progress in the understanding of the mechanisms respon-sible for the fibrogenic progression of chronic liver diseases. Several drugs believed to be hepatoprotective or antifibrotic agent as UDCA, betaine, vitamin E, lecithin, beta-carotene and selenium have been used in patients with NASH. Silybin is the main component of silymarin that is absorbed when linked whith a phytosome. This substance reduces in rats the lipid-peroxidation and the activaction of hepatic stellate cells. In humans, some non controlled data show that silybin is able to reduce insulin resistance, liver steatosis and plasma markers of liver fibrosis.
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PMID:The treatment of NAFLD. 1623 94

Oxidative stress leads to chronic liver damage. Silybin has been conjugated with vitamin E and phospholipids to improve its antioxidant activity. Eighty-five patients were divided into 2 groups: those affected by nonalcoholic fatty liver disease (group A) and those with HCV-related chronic hepatitis associated with nonalcoholic fatty liver disease (group B), nonresponders to treatment. The treatment consisted of silybin/vitamin E/phospholipids. After treatment, group A showed a significant reduction in ultrasonographic scores for liver steatosis. Liver enzyme levels, hyperinsulinemia, and indexes of liver fibrosis showed an improvement in treated individuals. A significant correlation among indexes of fibrosis, body mass index, insulinemia, plasma levels of transforming growth factor-beta, tumor necrosis factor-alpha, degree of steatosis, and gamma-glutamyl transpeptidase was observed. Our data suggest that silybin conjugated with vitamin E and phospholipids could be used as a complementary approach to the treatment of patients with chronic liver damage.
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PMID:The effect of a silybin-vitamin e-phospholipid complex on nonalcoholic fatty liver disease: a pilot study. 1741 Apr 54

Liver fibrosis may be considered as a dynamic and integrated cellular response to chronic liver injury. The activation of hepatic stellate cells and the consequent deposition of large amounts of extracellular matrix play a major role in the fibrogenic process, but it has been shown that other cellular components of the liver are also involved. Although the pathogenesis of liver damage usually depends on the underlying disease, oxidative damage of biologically relevant molecules might represent a common link between different forms of chronic liver injury and hepatic fibrosis. In fact, oxidative stress-related molecules may act as mediators able to modulate all the events involved in the progression of liver fibrosis. In addition, chronic liver diseases are often associated with decreased antioxidant defenses. Although vitamin E levels have been shown to be decreased in chronic liver diseases of different etiology, the role of vitamin E supplementation in these clinical conditions is still controversial. In fact, the increased serum levels of alpha-tocopherol following vitamin E supplementation not always result in a protective effect on liver damage. In addition, clinical trials have usually been performed in small cohorts of patients, thus making definitive conclusions impossible. At present, treatment with vitamin E or other antioxidant compounds could be proposed for nonalcoholic fatty liver disease (NAFLD), the most frequent hepatic lesion in western countries which can progress to nonalcoholic steatohepatitis and cirrhosis due to the production of large amounts of oxidative stress products. However, although some studies have shown encouraging results, multicentric and long-term clinical trials are needed.
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PMID:Vitamin E in chronic liver diseases and liver fibrosis. 1762 89

Data on the efficacy of herbal compounds are often burdened by the lack of appropriate controls or a limited statistical power. Treatments to prevent the progression of non alcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH) remain unsatisfactory. A total of 56 rabbits were arrayed into 7 groups fed with standard rabbit chow (SRC), SRC with 1% cholesterol, or each of the five experimental treatments (Kampo formulas 1% keishibukuryogan [KBG], 1% orengedokuto [OGT], and 1% shosaikoto [SST]; vitamin E [VE]; or pioglitazone [PG]) in a 1% cholesterol SRC. We analyzed changes after 12 weeks in plasma and liver lipid profiles, glucose metabolism, adipocytokines, oxidative stress, and liver fibrosis. Data demonstrated that all five treatments were associated with significant amelioration of lipid profiles, oxidative stress, and liver fibrosis compared to no supplementation. KBG was superior to VE and PG in the reduction of liver total cholesterol (P < 0.01) and lipid peroxidase levels (P < 0.05), urinary 8-hydroxy-2'-deoxyguanosine (P < 0.05), hepatic alpha-smooth muscle actin positive areas (P < 0.01) and activated stellate cells (P < 0.01). In conclusion, there was a statistically significant benefit of Kampo formulas (KBG in particular) on a dietary model of NAFLD/NASH. Future studies need to be directed at the mechanisms in the treatment of NASH.
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PMID:Evidence-based efficacy of Kampo formulas in a model of non alcoholic fatty liver. 1829 38


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