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)

Mycelia of the edible mushroom Lentinus edodes (shiitake) were cultivated in a solid medium, and two fractions were obtained by hot-water extraction (L.E.M.) and then ethanol extraction followed by Sephadex LH-20 column chromatography (ESMe). The L.E.M. and ESMe were then examined for their hepatoprotective effect on dimethylnitrosamine-injured mice. Both fractions decreased the blood aspartate aminotransferase and alanine aminotransferase levels, partially inhibited the overaccumulation of collagen fibrils, and suppressed the overexpression of genes for alpha-smooth muscle actin and/or heat-shock protein 47 in the mice. Both fractions also inhibited the morphologic change and proliferation of isolated rat hepatic stellate cells (HSCs), which play a central role in liver fibrosis, in a dose-dependent manner and without cytotoxicity. The direct interaction between the extracts and HSCs appears to be important for the hepatoprotective activity. Polyphenols contained in both fractions are considered to be potential candidates for expressing the hepatoprotective effects. The finding of antifibrotic activity in extracts from an edible mushroom is expected to be helpful in the development of hepatoprotective agents with few side effects.
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PMID:Hepatoprotective effect of extracts from Lentinus edodes mycelia on dimethylnitrosamine-induced liver injury. 1557 12

The purpose of this study was to evaluate the hepatoprotective and anti-fibrotic actions of crude extracts of Ganoderma tsugae (GTE) on chronic liver injury induced by carbon tetrachloride (CCl4) in rats. CCl4 (20%, 0.5 ml/rat) was given twice a week for 8 weeks, and animals received GTE through the whole experimental period. GTE showed obvious reducing actions on the elevated levels of glutamate-oxalate-transaminase (GOT) and glutamate-pyruvate-transaminase (GPT) caused by CCl4 at weeks 3, 6 and 8. Liver fibrosis in rats induced by CCl4 led to the drop of serum albumin and hepatic protein concentrations, while GTE increased serum albumin and hepatic protein concentrations. The CCl4-induced liver fibrosis may prolong the prothrombine time and increase albumin/globulin (A/G) ratio. GTE significantly decreased the prothrombine time and A/G ratio. Liver fibrosis induced by CCl4 markedly increased the weight of the spleen, hepatic water and hydroxyproline contents in rats, while GTE decreased the rat's spleen weights, hepatic water and hydroxyproline contents. All these results clearly demonstrated that GTE has hepatoprotective and anti-fibrotic activities.
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PMID:Effect of Ganoderma tsugae on chronically carbon tetrachloride-intoxicated rats. 1567 90

The Gangetic plain of West Bengal, India, has been engulfed by a disastrous environmental calamity of arsenic contamination of the ground water. Chronic arsenic toxicity caused by drinking arsenic-contaminated water has been one of the worst health hazards gradually affecting nine districts of West Bengal since the early 1980s. Over and above hyperpigmentation and keratosis,weakness, burning sensation of the eyes, swelling of the legs, liver fibrosis, chronic lung disease, gangrene of the toes, neuropathy, and skin cancer are other manifestations. Induction of cancer is frequently associated with DNA damage, changes in ploidy of cells, and non-random chromosome aberrations. Counteraction of these genotoxic and cytogenetic abnormalities with natural dietary polyphenols could be a useful strategy to combat arsenic-induced DNA damage and thereby cancer. A review of the literature showed that it is the antioxidant property of tea polyphenols that affords protection against various types of cancer. The present study was conducted to investigate whether the extracts of green tea and black tea (Darjeeling and Assam) as well as their polyphenols could ameliorate this arsenic-induced genotoxicity. The normal mammalian cell culture derived from male Chinese hamster lung fibroblast cells (V79) was used as the test system to assess the genotoxicity by micronucleus assay. The results showed that both green tea and black tea extracts have equal potential in modulating the arsenic-induced genotoxicity. This effect was perhaps induced by the constituent polyphenols present in green and black tea. In addition, the repair activity of the damaged cells was enhanced when treated with these tea extracts and their polyphenols. Thus, tea and its polyphenols may have a promising role in counteracting the devastating effects of arsenic.
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PMID:Arsenic-induced micronuclei formation in mammalian cells and its counteraction by tea. 1571 8

Apoptosis is one of the events that are involved in liver fibrogenesis. Thus, factors that affect apoptosis may be used to modulate liver fibrosis. We have recently reported that Salvia miltiorrhiza plays a protective role in carbon tetrachloride (CCl4)-induced hepatic fibrosis. In this study, we aimed to evaluate whether S. miltiorrhiza modulated CCl4-induced hepatic apoptosis in rats. Male Wistar rats were given orally either vehicle or water-extract of S. miltiorrhiza (50 mg kg(-1) twice daily) for nine weeks beginning from the start of CCl4 administration. A group of normal rats was included for comparison. Hepatocyte DNA fragmentation and cytosolic caspase-3 and caspase-8 activity were determined in the experimental animals. Hepatic cytosolic Bax, Bcl-2, cytochrome c, and calpain-mu expressions were measured by Western blot analysis. Hepatic mitochondrial glutathione levels were assessed by colorimetric assay. Compared with normal rats, rats receiving CCl4 alone showed profound DNA fragmentation associated with an increased cytosolic fraction of cytochrome c and calpain-mu protein expressions and a decreased mitochondrial glutathione level. In contrast, a decreased laddering of DNA fragmentation was noted in rats receiving CCl4 plus S. miltiorrhiza extract. The mitochondrial glutathione level was significantly increased in rats receiving CCl4 plus S. miltiorrhiza extract compared with those receiving CCl4 alone. Additionally, cytosolic caspase-3 activity and cytosolic fractions of Bax, Bcl-2, cytochrome c, and calpain-mu protein expressions were decreased in rats receiving CCl4 plus S. miltiorrhiza extract compared with those receiving CCl4 alone. The cytosolic caspase-8 activity in rats receiving CCl4 alone was no different from those receiving CCl4 plus S. miltiorrhiza extract. These results indicated that chronic administration of S. miltiorrhiza ameliorated CCl4-mediatd hepatic apoptosis in rats. This effect may be related to the antioxidant properties of S. miltiorrhiza.
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PMID:Water-soluble extract of Salvia miltiorrhiza ameliorates carbon tetrachloride-mediated hepatic apoptosis in rats. 1664 Aug 35

Schistosomiasis or bilharzia is a tropical disease caused by worms of the genus Schistosoma. The transmission cycle requires contamination of surface water by excreta, specific freshwater snails as intermediate hosts, and human water contact. The main disease-causing species are S haematobium, S mansoni, and S japonicum. According to WHO, 200 million people are infected worldwide, leading to the loss of 1.53 million disability-adjusted life years, although these figures need revision. Schistosomiasis is characterised by focal epidemiology and overdispersed population distribution, with higher infection rates in children than in adults. Complex immune mechanisms lead to the slow acquisition of immune resistance, though innate factors also play a part. Acute schistosomiasis, a feverish syndrome, is mostly seen in travellers after primary infection. Chronic schistosomal disease affects mainly individuals with long-standing infections in poor rural areas. Immunopathological reactions against schistosome eggs trapped in the tissues lead to inflammatory and obstructive disease in the urinary system (S haematobium) or intestinal disease, hepatosplenic inflammation, and liver fibrosis (S mansoni, S japonicum). The diagnostic standard is microscopic demonstration of eggs in the excreta. Praziquantel is the drug treatment of choice. Vaccines are not yet available. Great advances have been made in the control of the disease through population-based chemotherapy but these required political commitment and strong health systems.
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PMID:Human schistosomiasis. 1699 65

Alcohol is a risk factor for liver fibrosis and hepatocellular carcinoma. On the other hand, light alcoholic beverage consumption is believed to be beneficial because of the effects of both alcohol and nonalcoholic components of the beverage. Maotai is a commonly consumed beverage in China containing 53% alcohol. Epidemiological and experimental studies show that Maotai is less toxic to the liver than ethanol alone. To examine the differential effects of Maotai and ethanol, a low dose of Maotai or an equal amount of ethanol (53%, v/v in water, 5 ml/kg) were given to male mice daily for 1 week, and hepatic RNA was extracted for microarray analysis. Approximately 10% of genes on the liver-selective custom array (588 genes) were altered following Maotai or ethanol administration, but Maotai treated livers had fewer alterations compared with ethanol alone. Real-time reverse transcription-polymerase chain reaction confirmed and extended microarray results on selected genes. An induction of metallothionein and heme oxygenase-1 occurred with Maotai, which could not be explained by alcohol consumption alone, whereas the attenuation of ethanol responsive genes such as quinone dehydrogenase, DNA-ligase 1, IGFBP1, and IL-1beta suggests less liver injury occurred with Maotai. The expression of genes related to liver fibrosis, such as cytokeratin-18, was slightly increased by the high dose of ethanol, but was unchanged in the Maotai group. In summary, gene expression analysis indicates that Maotai induces a different response than ethanol alone. The dramatic induction of metallothionein and heme oxygenase-1 with Maotai could be important adaptive responses to reduce alcoholic liver injury.
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PMID:Differential effects between maotai and ethanol on hepatic gene expression in mice: Possible role of metallothionein and heme oxygenase-1 induction by maotai. 1701 77

Metabonomics has already been used to discriminate different pathological states in biological fields. The metabolic profiles of chronic experimental fibrosis and cirrhosis induction in rats were investigated using (1)H NMR spectroscopy of liver extracts and serum combined with pattern recognition techniques. Rats were continuously administered with thioacetamide (TAA) in the drinking water (300 mg TAA/L), and sacrificed on 1st, 2nd, and 3rd month of treatment. (1)H NMR spectra of aqueous and lipid liver extracts, together with serum were subjected to Principal Component Analysis (PCA). Liver portions were also subjected to histopathological examination and biochemical determination of malondialdehyde (MDA). Liver fibrosis and cirrhosis were progressively induced in TAA-treated rats, verified by the histopathological examination and the alterations of MDA levels. TAA administration revealed a number of changes in the (1)H NMR spectra compared to control samples. The performance of PCA in liver extracts and serum, discriminated the control samples from the fibrotic and cirrhotic ones. Metabolic alterations revealed in NMR spectra during experimental liver fibrosis and cirrhosis induction, characterize the stage of fibrosis and could be illustrated by subsequent PCA of the spectra. Additionally, the PCA plots of the serum samples presented marked clustering during fibrosis progression and could be extended in clinical diagnosis for the management of cirrhotic patients.
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PMID:Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats. 1711 14

Vascular system function involves complex interactions among the vascular endothelium, smooth muscle, the immune system, and the nervous system. The toxic metals cadmium (Cd), arsenic (As), and lead (Pb) can target the vascular system in a variety of ways, ranging from hemorrhagic injury to subtle pathogenic remodeling and metabolic changes. Acute Cd exposure results in hemorrhagic injury to the testis, although some strains of animals are resistant to this effect. A comparison of Cd-sensitive with Cd-resistant mouse strains showed that expression of the Slc39a8 gene, encoding the ZIP8 transporter, in the testis vasculature endothelium is responsible for this difference. Endogenously, ZIP8 is a Mn(2+)/HCO(3)(-)symporter that may also contribute to Cd damage in the kidney. Chronic Cd exposure is associated with various cardiovascular disorders such as hypertension and cardiomyopathy and it is reported to have both carcinogenic and anticarcinogenic activities. At noncytotoxic concentrations of 10-100nM, Cd can inhibit chemotaxis and tube formation of vascular endothelial cells. These angiostatic effects may be mediated through disruption of vascular endothelial cadherin, a Ca(2+)-dependent cell adhesion molecule. With regard to As, ingestion of water containing disease-promoting concentrations of As promotes capillarization of the liver sinusoidal endothelium. Because capillarization is a hallmark precursor for liver fibrosis and contributes to an imbalance of lipid metabolism, this As effect on hepatic endothelial cells may be a pathogenic mechanism underlying As-related vascular diseases. With regard to Pb, perinatal exposure may cause sustained elevations in adult blood pressure, and genetically susceptible animals may show enhanced sensitivity to this effect. Taken together, these data indicate that the vascular system is a critical target of metal toxicity and that actions of metals on the vascular system may play important roles in mediating the pathophysiologic effects of metals in specific target organs.
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PMID:The vascular system as a target of metal toxicity. 1794 43

Many factors could potentially affect the process of arsenic-induced liver fibrosis. The present study was undertaken to examine the effect of high fat diet on arsenic-induced liver fibrosis and preneoplastic changes. Mice were given sodium arsenite (As3+, 200 ppm) or sodium arsenate (As5+, 200 ppm) in the drinking water for 10 months, and provided a normal diet or a diet containing 20% added fat. Serum aspartate aminotransferase (AST), indicative of liver injury, was elevated in both arsenite and arsenate groups, and a high fat diet further increased these levels. Histopathology (H&E and Masson stain) showed that liver inflammation, steatosis (fatty liver), hepatocyte degeneration, and fibrosis occurred with arsenic alone, but their severity was markedly increased with the high fat diet. Total liver RNA was isolated for real-time RT-PCR analysis. Arsenic exposure increased the expression of inflammation genes, such as TNF-alpha, IL-6, iNOS, chemokines, and macrophage inflammatory protein-2. The expression of the stress-related gene heme oxygenase-1 was increased, while metallothionein-1 and GSH S-transferase-pi were decreased when arsenic was combined with the high fat diet. Expression of genes related to liver fibrosis, such as procollagen-1 and -3, SM-actin and TGF-beta, were synergistically increased in the arsenic plus high fat diet group. The expression of genes encoding matrix metalloproteinases (MMP2, MMP9) and tissue inhibitors of metalloproteinases (TIMP1, TIMP2) was also enhanced, suggestive of early oncogenic events. In general, arsenite produced more pronounced effects than arsenate. In summary, chronic inorganic arsenic exposure in mice produces liver injury, and a high fat diet markedly increases arsenic-induced hepatofibrogenesis.
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PMID:High dietary fat exacerbates arsenic-induced liver fibrosis in mice. 1829 43

Schistosomiasis is caused by trematode parasites of one of five species, Schistosoma mansoni, Schistosoma haematobium, Schistosoma japonicum, Schistosoma intercalatum, or Schistosoma mekongi, acquired via skin contact with fresh water containing infectious larval cercariae. Between 1 and 8 weeks after exposure, acute schistosomiasis presents as dermatitis, fever, fatigue, or eosinophilia. If untreated, long-term infection may cause anemia or undernutrition and may progress to liver fibrosis, portal hypertension, or hydronephrosis. Schistosomiasis represents a threat to residents and visitors in all endemic areas of Africa, Asia, and South America. Travelers should be made aware of infection risk if they become exposed to untreated fresh water. New immigrants and those returning to high-risk areas to visit friends and family should be screened for signs and symptoms of acute and chronic schistosomiasis. Physicians caring for travelers and immigrants must be familiar with the signs and symptoms of schistosomiasis and must be able to diagnose and treat it correctly.
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PMID:Schistosomiasis in travelers and immigrants. 1837 15


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