Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vitamin B(12) contains a cobalt complex and accumulates at high levels in the liver. Vitamin B(12) was examined for its hepatoprotective effect on dimethylnitrosamine-induced liver injury in mice. Vitamin B(12) decreased the blood levels of aspartate aminotransferase and alanine aminotransferase, and clearly inhibited the overaccumulation of collagen fibrils. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of the liver showed that the gene expression of alpha-smooth muscle actin and heat-shock protein 47, which are markers of fibrosis, were suppressed by vitamin B(12) administration. Our findings indicate that vitamin B(12) could be an effective hepatoprotective agent.
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PMID:Hepatoprotective effect of vitamin B12 on dimethylnitrosamine-induced liver injury. 1823 93

Silymarin, a standardized extract of the milk thistle (Silybum marianum), has a long tradition as a herbal remedy, and was introduced as a hepatoprotective agent a few years ago. However, the therapeutic effects of silymarin remain undefined. Carbon tetrachloride (CCl4) is a xenobiotic used extensively to induce oxidative stress and is one of the most widely used hepatic toxins for experimental induction of liver fibrosis in the laboratory. In this study, we investigated the restoration of the CCl4-induced hepatic fibrosis by high dose of silymarin in rats. After treatment with oil (as normal group; n = 6) or CCl4 [as model (n = 7) and therapeutic (n = 7) groups] by intragastric delivery for 8 weeks for the induction of liver fibrosis, the rats in the normal and model group were administered orally normal saline four times a week for 3 weeks whilst the therapeutic group received silymarin (200 mg/kg). The histopathological changes were observed with Masson staining. The results showed that the restoration of the CCl4-induced damage of liver fibrosis in the therapeutic group was significantly increased as compared to that in the model group. Moreover, silymarin significantly decreased the elevation of aspartate aminotransferase (AST), alanine aminotransferase, and alkaline phosphatase in serum, and also reversed the altered expressions of alpha-smooth muscle actin in liver tissue. Therefore, these findings indicated that silymarin may have the potential to increase the resolution of the CCl4-induced liver fibrosis in rats.
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PMID:Effects of silymarin on the resolution of liver fibrosis induced by carbon tetrachloride in rats. 1839 25

To assess the effect of infliximab, an anti-tumor necrosis factor (TNF)-alpha agent, on the carbon tetrachloride (CCl(4))-induced hepatic fibrosis in rats. Rats were randomized into three groups (n=9). The control group received only intraperitoneal (i.p.) olive oil. Hepatic fibrosis was induced by repeated i.p. injections of 1.5 ml/kg CCl(4) (1:3 mixture with olive oil) for 5 weeks in the remaining two groups which were also injected subcutaneous saline or 2 mg/kg infliximab. Infliximab reduced the levels of aspartate aminotransferase and alanine aminotransferase (p<0.05 for both). The scores of hepatic necrosis, inflammation and fibrosis, and expression of alpha-smooth muscle actin were lower in the infliximab-treated group than the CCI(4)-treated group (p<0.01, p<0.001, p<0.01, p<0.001, respectively). However, there was no significant difference in terms of liver tissue and plasma malondialdehyde, and serum TNF-alpha levels, while infliximab relatively reduced the level of transforming growth factor-beta(1) (373.0+/-153.1 vs. 280.8+/-127.1 pg/ml). Treatment with infliximab attenuated the necro-inflammation and fibrogenesis in the CCI(4)-induced hepatic fibrosis, and thus it might be effective as a therapeutic anti-fibrotic agent.
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PMID:Hepatoprotective effect of infliximab, an anti-TNF-alpha agent, on carbon tetrachloride-induced hepatic fibrosis. 1842 63

Morin, a plant-derived flavonoid, has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the protective effect of morin on hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats. Oral administration of morin remarkably prevented weight loss in the body and liver from DMN and inhibited the elevation of serum alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin levels. For the evaluation of hepatic fibrosis-related factors, we investigated expressions of collagen type I, transforming growth factor beta(1) (TGF-beta(1)), and alpha-smooth muscle actin (alpha-SMA) in mRNA and protein levels. We observed that morin significantly reduced the expression of collagen type I, TGF-beta(1), and alpha-SMA on hepatic fibrosis induced by DMN. Taken together, this study demonstrated that morin showed hepatoprotective and antifibrogenic effects against DMN-induced hepatic injury. This suggests that morin may be useful in preventing the development of hepatic fibrosis and cirrhosis.
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PMID:Protective effect of morin on dimethylnitrosamine-induced hepatic fibrosis in rats. 1862 40

The pathophysiological mechanisms of thioacetamide (TAA)-induced hepatic fibrogenesis are not yet fully understood. In particular, the role of hepatic stellate cells (HSCs) remains unclear. We therefore examined proliferation and transdifferentiation of HSC as well as the underlying molecular mechanisms in TAA-induced fibrosis. Hepatic fibrogenesis was induced in mice by addition of TAA to drinking water. Liver damage was determined by assessment of alanine aminotransferase and aspartate aminotransferase levels, and measurement of collagen deposition. Additionally, expression patterns of alpha-smooth muscle actin, glial fibrillary acidic protein (GFAP, specific hepatic biomarker for HSC), cysteine- and glycine-rich protein 2 (CRP2, specific marker of HSC transdifferentiation), tissue inhibitor of metalloproteinases-1, matrix metalloproteinase-9 (MMP-9), interleukins (IL-1beta, IL-6), platelet-derived growth factors (PDGF-B, PDGF-D) , tumor necrosis factor (TNF)-alpha, and (transforming growth factor (TGF)-beta1 were assessed by real-time PCR. Transcription of GFAP and CRP2 were transiently upregulated during TAA-induced fibrogenesis (punctum maxima (p.m.) week 10 for GFAP and week 14 for CRP2). Similar transient expression patterns were demonstrated for IL-1beta, IL-6, TGF-beta1, and PDGF-B (p.m. week 12) whereas TNF-alpha and PDGF-D continuously increased with ongoing liver injury. In particular, not only neutrophil granulocytes, but also macrophages and leukocytes served as a major source for MMP-9 expression. GFAP and CRP2 expression patterns demonstrated transiently increased HSC-activation during TAA-induced hepatic fibrogenesis. The rate of increase of transcription of GFAP correlated best with PDGF-B, whereas CRP2 levels correlated with PDGF-B, PDGF-D, and IL-1beta expression. This study demonstrates for the first time that transiently increased activation patterns of HSC are observed in toxically induced hepatic fibrosis. Thus, TAA in drinking water is an effective and elegant model to induce reproducible states of liver fibrosis without parenchymal damage in mice.
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PMID:Activation of hepatic stellate cells is associated with cytokine expression in thioacetamide-induced hepatic fibrosis in mice. 1879 50

Bidens bipinnata L. is well known in China as a traditional Chinese medicine and has been used to treat hepatitis in clinics for many years. In a previous study we found that total flavonoids of Bidens bipinnata L. (TFB) had a protective effect against carbon tetrachloride (CCl4)-induced acute liver injury in mice. Now this study was designed to investigate its therapeutic effect against CCl4-induced liver fibrosis in rats and to determine, in part, its mechanism of action. The liver fibrosis model was established by subcutaneous injection of 50% CCl4 twice a week for 18 weeks. TFB (40, 80 and 160 mg kg(-1)) was administered by gastrogavage daily from the 9th week. The results showed that TFB (80 and 160 mg kg(-1)) treatment for 10 weeks significantly reduced the elevated liver index (liver weight/body weight) and spleen index (spleen weight/body weight), elevated levels of serum transaminases (alanine aminotransferase and aspartate aminotransferase), hyaluronic acid, type III procollagen and hepatic hydroxyproline. In addition, TFB markedly inhibited CCl4-induced lipid peroxidation and enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. Moreover, TFB (80 and 160 mg kg(-1)) treatment improved the morphologic changes of hepatic fibrosis induced by CCl4 and suppressed nuclear factor (NF)-kappaB, alpha-smooth muscle actin (SMA) protein expression and transforming growth factor (TGF)-beta1 gene expression in the liver of liver fibrosis of rats. In conclusion, TFB was able to ameliorate liver injury and protect rats from CCl4-induced liver fibrosis by suppressing oxidative stress. This process may be related to inhibiting the induction of NF-kappaB on hepatic stellate cell activation and the expression of TGF-beta1.
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PMID:Protective effects of total flavonoids of Bidens bipinnata L. against carbon tetrachloride-induced liver fibrosis in rats. 1881 33

In this study, the protective effect of extract of Hsian-tsao (Mesona procumbens) (EHT) against liver fibrogenesis in carbon tetrachloride (CCl(4))-injured rats was evaluated. The inhibitory effect of oleanolic acid (OA) and ursolic acid (UA), which are the active compounds in EHT, on the activation of hepatic stellate cells (HSC) was also determined. The results showed that EHT at a dosage of 1.2g/kg of b.w. significantly reduced the liver injury induced by CCl(4) in rats. It also decreased the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and the deposition of collagen in the liver. Oral administration of EHT reduced the levels of alpha-smooth muscle actin (alpha-SMA) and the activity of metalloproteinases (MMPs) in rats injured by treatment with CCl(4). In addition, we performed experiments with the rat hepatic stellate cell line HSC-T6 in which we induced the expression of MMP-2 and alpha-SMA with phorbol-12-myristate-13-acetate (PMA). Treating these cells with OA (20microM) or UA (10microM) caused a decrease in the levels of both proteins. Taken together, our data indicate that EHT can efficiently inhibit CCl(4)-induced liver fibrosis in rats. EHT may therefore be a useful functional food for preventing liver fibrosis.
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PMID:Hsian-tsao (Mesona procumbens Heml.) prevents against rat liver fibrosis induced by CCl(4) via inhibition of hepatic stellate cells activation. 1892 13

The contribution of metabolic factors to the severity of liver disease is not completely understood. In this study, apolipoprotein E-deficient (ApoE-/-) mice were evaluated to define potential effects of hypercholesterolemia on the severity of carbon tetrachloride (CCl4)-induced liver injury. Under baseline conditions, hypercholesterolemic ApoE-/- mice showed increased hepatic oxidative stress (SOD activity/4-hydroxy-2-nonenal immunostaining) and higher hepatic TGF-beta1, MCP-1, and TIMP-1 expression than wild-type control mice. After CCl4 challenge, ApoE-/- mice exhibited exacerbated steatosis (Oil Red O staining), necroinflammation (hematoxylin-eosin staining), macrophage infiltration (F4/80 immunohistochemistry), and fibrosis (Sirius red staining and alpha-smooth muscle actin immunohistochemistry) and more severe liver injury [alanine aminotransferase (ALT) and aspartate aminotransferase] than wild-type controls. Direct correlations were identified between serum cholesterol and hepatic steatosis, fibrosis, and ALT levels. These changes did not reflect the usual progression of the disease in ApoE-/- mice, since exacerbated liver injury was not present in untreated age-paired ApoE-/- mice. Moreover, hepatic cytochrome P-450 expression was unchanged in ApoE-/- mice. To explore potential mechanisms, cell types relevant to liver pathophysiology were exposed to selected cholesterol-oxidized products. Incubation of hepatocytes with a mixture of oxysterols representative of those detected by GC-MS in livers from ApoE-/- mice resulted in a concentration-dependent increase in total lipoperoxides and SOD activity. In hepatic stellate cells, oxysterols increased IL-8 secretion through a NF-kappaB-independent mechanism and upregulated TIMP-1 expression. In macrophages, oxysterols increased TGF-beta1 secretion and MCP-1 expression in a concentration-dependent manner. Oxysterols did not compromise cell viability. Taken together, these findings demonstrate that hypercholesterolemic mice are sensitized to liver injury and that cholesterol-derived products (i.e., oxysterols) are able to induce proinflammatory and profibrogenic mechanisms in liver cells.
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PMID:Increased susceptibility to exacerbated liver injury in hypercholesterolemic ApoE-deficient mice: potential involvement of oxysterols. 1913 84

The asialoglycoprotein (ASGP) receptor is an abundant hepatocyte-specific receptor involved in receptor-mediated endocytosis. This receptor's abundance and function is decreased by chronic ethanol administration prior to the appearance of pathology such as necrosis or inflammation. Hence, this study aimed to determine if ASGP receptor function is required to protect against liver injury by utilizing a knockout mouse model lacking functional ASGP receptor in the setting of carbon tetrachloride (CCl(4)) hepatotoxicity. Briefly, ASGP receptor-deficient (RD) mice and wild-type (WT) mice were injected with 1ml/kg body weight of CCl(4). In the subsequent week, mice were monitored for liver damage and pathology (aspartate transaminase (AST), alanine transaminase (ALT) and light microscopy). The consequences of CCl(4) injection were examined by measuring alpha-smooth muscle actin (alpha-SMA) deposition, contents of malondialdehyde and the percentage of apoptotic hepatocytes. After CCl(4) injection, RD mice showed increased liver pathology together with significantly increased activities of AST and ALT compared to that in WT mice. There were also significantly more apoptotic bodies, lipid peroxidation and deposition of alpha-SMA in RD mice versus WT mice following CCl(4) injection. Since these two mouse strains only differ in whether or not they have the ASGP receptor, it can be concluded that proper ASGP receptor function exerted a protective effect against CCl(4) toxicity. Thus, receptor-mediated endocytosis by the ASGP receptor could represent a novel molecular mechanism that is responsible for subsequent liver health or injury.
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PMID:Carbon tetrachloride-induced liver damage in asialoglycoprotein receptor-deficient mice. 1918 65

The aim of this study was to evaluate the effects of methylene blue against cholestatic oxidative stress and liver damage after ligation of the common bile duct in male Wistar rats. Eight animals were included in each of the following five groups: untreated control, methylene blue control, sham-operated, bile-duct ligation, and bile-duct ligation plus methylene blue. Methylene blue was administered intraperitoneally for 14 days at a daily dose of 2mg/kg per day. All rats were sacrificed 2 weeks following the experimental treatment and the livers of all groups were examined biochemically and histopathologically. The severity of cholestasis and hepatic injury were determined by changes in the plasma, including enzymatic activities: aspartate aminotransferase, alanine aminotransferase, gamma glutamine transferase, and also bilirubin levels. Malondialdehyde, nitric oxide and superoxide dismutase were measured to indicate the oxidative status in the liver tissue. Myeloperoxidase activity and levels of tissue hydroxyproline were determined as measures of neutrophil activation and collagen accumulation, respectively. Liver damage was significantly prevented in the bile-duct ligated rats treated with methylene blue compared with the control bile-duct ligated rats without methylene blue. Treatment with methylene blue markedly reduced activities of serum transaminase, gamma glutamine transferase and bilirubin levels as compared to bile-duct ligated rats without methylene blue. Positive immunolabelling for alpha-smooth muscle actin (alpha-SMA) was increased, especially in vascular smooth muscle cells, fibrotic septa and also around the proliferated bile ducts, after bile-duct ligation. Only weak alpha-SMA immunolabelling was seen in livers of rats treated with methylene blue. These results indicate that methylene blue can attenuate hepatic damage in extrahepatic cholestasis by reducing oxidative stress and inflammatory processes.
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PMID:Effects of methylene blue in reducing cholestatic oxidative stress and hepatic damage after bile-duct ligation in rats. 1921 52


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