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

Several beneficial effects of splenectomy on the liver integrity have been recently reported by both experimental and clinical studies. However, the effects of splenectomy on hepatic functional reserve and structural damage in patients with chronic hepatitis C (CHC) were not studied by objective evidence. The aim of this study was to assess the effect of splenectomy on hepatic functional reserve and structural damage in patients with CHC by non-invasive serum markers. The study involved 22 patients with histopathological diagnosis of CHC undergoing splenectomy for treatment of associated hypersplenism. The hepatic functional reserve and structural damage markers were assessed before and after splenectomy surgery on the 2nd and 60th postoperative days by aspartate aminotransferase to alanine aminotransferase (AST/ALT ratio), AST to platelet ratio index (APRI) and serum levels of gamma-glutamyl transferase (GGT), hyaluronic acid (HA), type IV collagen (CIV) and tissue inhibitor of metalloproteinase-1 (TIMP-1). After splenectomy, the levels of serum HA showed a significant decrease in relation to the preoperative values both in PO-1 (mean pre-splenectomy: 272+/-88.6 versus 185+/-77.4 ng/ml; P=0.01) and PO-2 (169+/-58.1 ng/ml; 0.017). The levels of type IV collagen showed a significant decrease in relation to the preoperative values both in PO-1 (mean pre-splenectomy: 208+/-134 versus 125+/-100 ng/ml; P=0.01) and PO-2 (121+/-74.7 ng/ml; P=0.02). Serum levels of TIMP-1 also showed a significant decrease in relation to the preoperative values both in PO-1 (mean pre-splenectomy: 764+/-571 versus 261+/-195 ng/ml; P=0.006) and PO-2 (149+/-110.1 ng/ml; P=0.004). There was no significant difference between PO-1 and PO-2 mean values for each of those serum markers. This study found that splenectomy induced a reduction of biochemical markers of liver functional reserve and fibrosis in patients with chronic hepatitis C which reflect a change in the processes involved in of liver fibrosis. However, it cannot be concluded whether this reflects a change in the rate of its progression or a prevention of further fibrosis.
 ...
PMID:A study of the effect of splenectomy on hepatic functional reserve and structural damage in patients with chronic hepatitis C virus infection by non-invasive serum markers. A prospective study. 1866 98

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.
 ...
PMID:Activation of hepatic stellate cells is associated with cytokine expression in thioacetamide-induced hepatic fibrosis in mice. 1879 50

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.
 ...
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 hepatoprotective properties of Artemisiae capillaris herba (AC) and Picrorrhiza rhizoma (PR) are well known. The aim of this study was to determine the optimal composition of AC and PR mixtures for better complimentary or alternative regimens in reducing the level of hepatic fibrosis. Ten weeks of carbon tetrachloride injections caused subacute hepatic damage, manifested as significantly less body weight gain and hepatic protein content, and a higher liver weight, serum aspartate aminotransferase and alanine aminotransferase levels, hepatic malondialdehyde (an index for lipid peroxidation), and hydroxyproline (an index for collagen synthesis) concentrations. The carbon tetrachloride-induced toxic effects were inhibited by 11 different AC/PR mixtures as well as the single AC or PR treatment. More favorable effects were detected in all mixed-formulation groups compared with the AC or PR single formulations. Moreover, the AC/PR 2:1 formulation showed the most favorable hepatoprotective activity. The AC and PR mixtures showed good synergic hepatoprotective activity that was attributed to increasing free-radical scavenging ability. Among the 11 types of mixed formula tested in this study, the AC/PR 2:1 formulation had the most impressive synergic effects on inhibiting the subacute hepatic damage induced by carbon tetrachloride in rats and showed more favorable effects than with an equal dose of silymarin.
 ...
PMID:Hepatoprotective effects of Artemisiae capillaris herba and Picrorrhiza rhizoma combinations on carbon tetrachloride-induced subacute liver damage in rats. 1908 19

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.
 ...
PMID:Effects of methylene blue in reducing cholestatic oxidative stress and hepatic damage after bile-duct ligation in rats. 1921 52

The goal of this study was to evaluate the possible protective effects of sphingosylphosphorylcholine (SPC) against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. Fifty-six animals were included in each of the following 7 groups: control, SPC control, phosphate-buffered solution control, sham operated, bile duct ligation (BDL), BDL plus phosphate-buffered solution, and BDL plus SPC. Sphingosylphosphorylcholine was administered 14 days at a daily dose of 2 microm/mL intraperitoneally. The severity of cholestasis and hepatic injury was determined by changes in the plasma enzyme activities of aspartate aminotransferase, alanine aminotransferase, gama glutamin transferase, and levels of total bilirubin and direct bilirubin. Malondialdehyde, nitric oxide, and superoxide dismutase were determined to evaluate the oxidative status in the liver tissue. Myeloperoxidase activity and levels of tissue hydroxyproline were determined to assess neutrophil activation and collagen accumulation, respectively. Treatment with SPC markedly reduced serum transaminase activities as compared to BDL rats. Sphingosylphosphorylcholine also inhibited the increase in liver malondialdehyde; nitric oxide levels significantly and also attenuated the depletion of superoxide dismutase in the liver after BDL. Similarly, the increase in tissue myeloperoxidase activity and hydroxyproline owing to BDL was also attenuated by the SPC treatment. These data were supported by histopathologic findings. The alpha-smooth muscle actin-positive cells in the BDL were observed to be reduced with the SPC treatment. In conclusion, these findings suggested that SPC can attenuate hepatic damage in extrahepatic cholestasis by prevention of oxidative stress, and inflammatory process. All these findings suggest that SPC may be a promising new therapeutic agent for cholestatic liver injury.
 ...
PMID:Effects of sphingosylphosphorylcholine against cholestatic oxidative stress and liver damage in the common bile duct ligated rats. 1936 29

The effect of relaxin administration before (prevention) or after (treatment) the establishment of hepatic fibrosis in a mouse model was examined. In the prevention study, relaxin reduced collagen and smooth muscle actin content and significantly reduced serum levels of the liver enzymes alanine aminotransferase and aspartate aminotransferase. In the treatment study, administration of relaxin for 1 week reduced collagen and smooth muscle actin but not liver enzyme levels. Relaxin administered for 2 weeks had no significant effect. In conclusion, the data suggest that relaxin treatment before fibrosis can reduce collagen and improve liver function but that there is little effect of short-term relaxin treatment after fibrosis is established.
 ...
PMID:Relaxin reduces fibrosis in models of progressive and established hepatic fibrosis. 1941 17

A herbal preparation "Compound Codyceps-TCM-700C (CC-700C)" was tested for hepatoprotective effect against the carbon tetrachloride induced liver damages in Sprague-Dawley rat model for a period of 6-weeks. Two dosage levels of CC-700C, respectively 286.2 mg/kg-bw (L-TCM) and 2862 mg/kg-bw (H-TCM), and a positive control Silymarin (Sigma) were used to compare their therapeutic effect. Both CC-700C's and Silymarin showed nontoxic in nature, as evidenced by body weight gain, organ weights and appearance including liver, spleen, and kidney. The activities of aspartate aminotransferase (AST) and alanine-aminotransferase (ALT) were more effectively suppressed by CC-700C than Silymarin. In addition, all levels of serum bilirubin, serum albumin, triglyceride (TG), total cholesterol (TC), platelet count (PLT), and prothrombin time (PT) except TG were shown effectively restored to normal values by CC-700C and Silymarin. Moreover, although levels of glutathione (GSH), glutathione reductase (GSH-Rd), and superoxide dismutase (SOD) were equally maintained by these three preparations, glutathione peroxidase (GSH-Px) was suppressed only by H-TCM, and SOD only by Silymarin. In contrast, the activity of catalase efficiently recovered to control level on administration of CC-700C, being far better than Silymarin. Finally the liver collagen content, an indication of fibrosis, was also significantly suppressed by CC-700C, better effect was by L-TCM, but both levels were superior to Silymarin. Conclusively, the herbal preparation "Compound Cordyceps TCM-700C" is a potent hepatoprotective preparation. For therapeutic use, a dosage of 286.2 mg/kg-bw would be sufficiently effective.
 ...
PMID:Compound Cordyceps TCM-700C exhibits potent hepatoprotective capability in animal model. 1959 25

A series of methylenedioxybenzene compounds were synthesized and found to have hepatoprotective effects in chemical-induced hepatotoxicity models. The purpose of the present study was to investigate the anti-fibrotic effects of a synthetic methylenedioxybenzene compound, CW209292, using the dimethylnitrosamine (DMN)-induced chronic liver injury model in rats. Liver injuries were induced in Sprague Dawley rats by injection of DMN (intraperitoneally, 10 microl/kg) 3 times per week for 4 weeks. The rats were treated with CW209292 (per os, 25 or 75 mg/kg/d) for 4 weeks. Treatment of rats with DMN for 4 weeks resulted in significant decreases in serum albumin levels, whereas concomitant treatment with CW209292 prevented these decreases. CW209292 treatment also shortened prothrombin time prolonged by DMN, providing evidence that the agent was active in preserving liver function against DMN insult. DMN treatment caused marked increases in plasma bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT), and hyaluronic acid levels; CW209292 treatment reversed these increases. CW209292 also significantly reduced hepatic hydroxyproline content as well as hepatic fibrosis and inflammation in histological examination. Additionally, immunochemically detectable hepatic collagen type IV and alpha-smooth muscle actin levels were decreased by CW209292 treatment. Proliferation of hepatic stellate cells isolated from DMN-treated rats was inhibited by CW209292. Furthermore, tumor growth factor (TGF)-beta1 mRNA expression was increased in DMN-treated rats, whereas CW209292 treatment prevented these increases. These results suggest that CW209292 exhibits anti-fibrotic effects in Sprague Dawley rats with DMN-induced hepatic fibrosis by blocking the mRNA expression of TGF-beta1 and subsequent inhibition of the proliferation of hepatic stellate cells.
 ...
PMID:Anti-fibrotic effects of a methylenedioxybenzene compound, CW209292 on dimethylnitrosamine-induced hepatic fibrosis in rats. 1965 75

Cirrhosis is the most common end stage of liver diseases, and there are no effective treatment methods. Here we evaluated the effect of endothelial progenitor cell (EPC) transplantation from rat bone marrow (BM) on the development of cirrhosis induced by carbon tetrachloride (CCl(4)). Ex vivo generated, characterized, and cultivated rat BM-derived EPCs were identified by their vasculogenic properties in vitro. EPCs from male rats were transplanted into female rats via the intraportal vein 12 weeks after they had been challenged with CCl(4), and the rats were killed 16 weeks later. The control rats received only a saline infusion. The fibrosis index and donor cell engraftment were assessed after EPC transplantation. After transplantation via the portal vein, PKH26 labeling, polymerase chain reaction, and in situ hybridization analysis revealed that the donor EPCs had adhered to the vasolateral surfaces of blood vessels and established in the liver. EPCs reduced the expression of alpha-smooth muscle actin, collagen III, and transforming growth factor beta (P < 0.05) as well as levels of aspartate aminotransferase, alanine aminotransferase, and total bilirubin in the serum (P < 0.05), but at the same time they increased the levels of albumin and Ki67. CCl(4) treatment increased the international prothrombin ratio (P < 0.05) and reduced albumin levels, whereas EPCs restored these parameters to normal levels. These results suggest that EPC transplantation could play a role in regulating hepatocyte regeneration and ameliorating established liver cirrhosis.
 ...
PMID:Transplanted endothelial progenitor cells ameliorate carbon tetrachloride-induced liver cirrhosis in rats. 1971 41


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>