Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relationships between serum thiobarbituric acid (TBA) level and smoking, alcohol drinking, differences in food intake with alcohol drinking, serum vitamin C (VC) and E (VE) were studied in 283 non-treated men (aged 20-69 years) who visited a human dock conducted in an urban area of Hyogo prefecture in 1989-1991 (annually May-July). The results were as follows: 1. An effect of smoking on serum TBA level was not observed. 2. The subjects were divided into three groups according to weekly sake intake levels, i.e., non-drinkers including ex-drinkers (ND), mild drinkers (MD, weekly sake intake: < or = 1260 ml), and heavy drinkers (HD, > 1260 ml). The serum TBA level of HD, but not of MD, was significantly higher than that of ND. 3. Serum TBA level had significant positive correlations with age, GPT, gamma-GTP, TC (total cholesterol), TG (triglycerides), PL (phospholipids), total serum lipids (TLP, i.e., TC+TG+PL), VE, eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6), but had no significant correlations with VC and VE/TLP. 4. The subjects (N+M) D, which included ND and MD, and those of HD were divided respectively into three groups according to weekly food intake levels, i.e., non-intake group (NF), low frequent intake group (LF, 1-3 days/week), and high frequent intake group (HF, > or = 4 days/week). The fish intake level of HD was significantly higher than that of (N+M) D, while the intake levels of vegetables, fruits and soft drinks of HD were significantly lower than those of (N+M) D. 5. Serum TBA level, GOT, GPT, gamma-GTP, TG, PL, TLP, VE, EPA and DHA of HD were significantly higher than those of (N+M) D. On the other hand, VC of HD was significantly lower than that of (N+M) D. 6. When the subjects of (N+M) D were divided into three groups according to weekly fish intake levels as mentioned above, serum TBA level, EPA and DHA of HF in (N+M) D were significantly higher than those of NF in (N+M) D. 7. Serum TBA level of HD in non-fish intake group was significantly higher than that of (N+M) D in the same group. These results suggest that increased serum TBA level in HD is closely related to the increased intake frequency of fish in addition to the effect of alcohol drinking.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Relationships between serum lipid peroxide level (serum TBA level) and smoking, alcohol drinking, food frequency, serum vitamin C and E in subjects with multiphasic screening]. 802 8

As chronic liver disease progresses, an imbalance occurs between synthesis and breakdown of extracellular matrix (ECM). Matrix metalloproteinases (MMPs) are involved in degrading ECM while tissue inhibitors of metalloproteinases (TIMPs) prevent their fibrolytic action. We determined if plasma levels of MMP-2, TIMP-1 and TIMP-2 are related to liver histology in patients with chronic hepatitis C. Plasma MMP-2, TIMP-1 and TIMP-2 levels were measured in 43 patients with chronic hepatitis C. Plasma levels of MMP-2, TIMP-1 and TIMP-2 and serum ALT were correlated with liver biopsy score and specificity and sensitivity of the assays in detecting advanced liver disease were calculated from ROC analysis. Plasma TIMP-1 was significantly correlated with histological activity index (r = 0.45), portal inflammation (r = 0.48), periportal necrosis (r = 0.34) and focal necrosis (r = 0.38). Plasma TIMP-2 was significantly correlated with fibrosis (r = 0.43) and confluent necrosis (r = 0.41). Using ROC analysis both TIMP-1 and TIMP-2 had significant diagnostic ability in detecting advanced liver disease (Area under the curve 0.73 for both, p 0.015 and 0.036 respectively). A normal plasma TIMP-1 excluded advanced liver disease. Neither plasma MMP-2 or serum ALT were related to fibrosis or to histological activity index. With increased severity of liver disease in chronic hepatitis C there is increased plasma levels of TIMPs -1 and -2. Plasma TIMP-1 and TIMP-2 are sensitive and to a lesser extent specific in detecting advanced liver disease in chronic hepatitis C and could be used in preference to serum ALT.
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PMID:Plasma levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinases -1 and -2 (TIMP-1 and TIMP-2) as noninvasive markers of liver disease in chronic hepatitis C: comparison using ROC analysis. 1008 Jan 60

The purpose of this study is to evaluate the acute and chronic toxicology of oral intake of fish oil (omega-3 fatty acid) and garlic combination food supplements. These supplements were proven to have beneficial effects on the lipid profile. Therefore, it is important to evaluate the potential long-term effects of fish oil and garlic combination supplements on the biochemistry of organ structure and function. The hypothesis to be tested was that acute and chronic high-dose supplements of fish oil and garlic may not adversely affect organ histology but may influence certain metabolic activities. A double-blind, placebo-controlled study was carried out using 28 Sprague Dawley rats separated into a placebo group (16 rats) and a supplement group (12 rats). The supplement group received the ingredients in chow inserts at a dosage that was equivalent to three times the maximum safe daily dosage for fish oil and the usual daily dosage for garlic (the maximum safe daily dosage recommended by the United States Food And Drug Administration for a 70-kg human is a total of 3 g/day intake of EPA and HDA omega-3 fatty acids from conventional and dietary sources. The usual daily garlic usage is garlic powder = 1200 mg). The study was conducted over a period of 12 months with evaluations performed at baseline, 2 months, 6 months, and 12 months. Results confirm the expected acute triglyceride, total cholesterol and LDL suppression at these higher dosages in the supplement group. Acutely and chronically, there were no differences in external appearance, level of activity, daily food consumption, blood cell count, kidney function, thyroid function, prothrombin time (PT), and activated partial prothrombin time (PTT), which remained within normal ranges in the supplement group. Organ histology remained unchanged. Although during the chronic toxicity period the triglyceride and LDL suppression persisted, it was noted that total cholesterol and HDL levels increased. The increase in cholesterol and HDL in the supplement group during chronic toxicity periods is simultaneous with loss of suppression of plasma levels of other liver function marker enzymes, ALT and AST, which are not involved in cholesterol synthesis. This possibly suggests that other liver enzymes involved in cholesterol synthesis, such as HMG-co A reductase, follow a similar escape from suppression.
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PMID:Acute and chronic toxicity study of fish oil and garlic combination. 1172 96

AIM:To investigate clinic effects of Fuzheng Huayu 319 recipe (319 recipe) on liver fibrosis in chronic hepatitis B.METHODS:Ninety-five patients with chronic hepatitis B were divide into the treated (63 cases) and control (32 cases) group, and orally administrated with 0.5g 319 capsule or 0.5g Dahuang Zhachong pill tid for 3 months, respectively. The liver functions and serological fibrotic markers were observed before and after treatment, 12 cases in the treated group were examined with liver biopsy.RESULTS:Three hundreds nineteen recipe could remarkably decreased serum ALT level and total bilirubin and significantly improve serum albumin and A/G ratio. Its effects were better than Dahuang Zhachong pill. Before treatment, patients'serum monamine oxidase activities, tissue inhibitor of metalloproteinase (TIMP)-1, procollagen type and laminin were all higher than those of health peoples. These levels decreased remarkably after treatment,and urine hydroxyproline level increased significantly (P < 0.001-0.05). Compared with the control, the improvement in treated group was better than that in the control except TIMP-1. According to the scoring system for staging of chronic hepatitis, the fibrotic extents of 7 cases among 12 cases examined by liver biopsy decreased remarkably (1 case decreased by 3 scores, 5 by 2 scores, 1 by 1 score).CONCLUSION:Fuzheng Huayu 319 recipe had good therapeutic effects on chronic hepatitis B, it could reverse the development of liver fibross to some extent. In general its effects were better than that of Dahuang Zhachong pill.
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PMID:Effects of Fuzheng Huayu 319 recipe on liver fibrosis in chronic hepatitis B. 1181 18

Pioglitazone, a new thiazolidinedione agent,has been shown to increase insulin sensitivity in clinical trials. Pioglitazone HCI was rapidly absorbed within one hour, achieved peak concentrations at 2-3 h, and was eliminated from serum at 24-36 h. Pioglitazone demonstrated dose-dependent pharmacokinetics. Food did not significantly affect the pharmacokinetic profile of pioglitazone. The pharmacokinetic profile of sulfonylurea agents was not significantly altered by concurrent administration with pioglitazone. Pharmacokinetic studies in healthy volunteers and in patients with type 2 diabetes indicated that pioglitazone may be administered once daily. In patients with type 2 diabetes, pioglitazone as monotherapy and in combination with sulfonylureas or an alpha-glucosidase inhibitor significantly reduced fasting blood glucose, HbA1c, triglycerides, and free fatty acids, and significantly increased HDL-cholesterol. Pioglitazone demonstrated either minor increases or decreases in cholesterol with no adverse effect on LDL-cholesterol. No patients experienced jaundice or ALT elevations > or = three times the upper limit of normal. Adverse events were mild and transient; all subjects returned to their baseline health status or laboratory tests upon withdrawal from, or completion of, the studies. Based upon these preliminary studies, full-scale clinical investigations were conducted in Japan, the United States, and Europe. As a result, in many countries pioglitazone has gained approval for use in patients with type 2 diabetes.
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PMID:Pioglitazone: a review of Japanese clinical studies. 1190 Mar 11

The effects of halothane, isoflurane and sevoflurane anaesthesia on hepatic function and hepatocellular damage were investigated in dogs, comparing the activity of hepatic enzymes and bilirubin concentration in serum. An experimental study was designed. Twenty-one clinically normal mongrel dogs were divided into three groups and accordingly anaesthetized with halothane (n = 7), isoflurane (n = 7) and sevoflurane (n = 7). The dogs were 1-4 years old, and weighed between 13.5 and 27 kg (18.4 +/- 3.9). Xylazine HCI (1-2 mg/kg) i.m. was used as pre-anaesthetic medication. Anaesthesia was induced with propofol 2 mg/kg i.v. The trachea was intubated and anaesthesia maintained with halothane, isoflurane or sevoflurane in oxygen at concentrations of 1.35, 2 and 3%, respectively. Intermittent positive pressure ventilation (tidal volume, 15 ml/kg; respiration rate, 12-14/min) was started immediately after intubation and the anaesthesia lasted for 60 min. Venous blood samples were collected before pre-medication, 24 and 48 h, and 7 and 14 days after anaesthesia. Serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH GGT) activities and bilirubin concentration were measured. Serum AST, ALT and GGT activities increased after anaesthesia in all groups. In the halothane group, serum AST and ALT activities significantly increased all the time after anaesthesia compared with baseline activities. But in the isoflurane group AST and ALT activities increased only between 2 and 7 days, and in the sevoflurane group 7 days after anaesthesia. GGT activity was increased in the halothane group between 2 and 7 days, and in the isoflurane and sevoflurane groups 7 days after anaesthesia. All dogs recovered from anaesthesia without complications and none developed clinical signs of hepatic damage within 14 days. The results suggest that the use of halothane anaesthesia induces an elevation of serum activities of liver enzymes more frequently than isoflurane or sevoflurane from 2 to 14 days after anaesthesia in dogs. The effects of isoflurane or sevoflurane anaesthesia on the liver in dogs is safer than halothane anaesthesia in dogs.
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PMID:Hepatic effects of halothane, isoflurane or sevoflurane anaesthesia in dogs. 1515 22

1. Acute liver injury is a severe disease in which metabolic homeostasis is affected. The presence of liver cell death triggers a cascade of inflammatory responses leading to various degrees of liver damage. The pathophysiology of liver injury is complex, involving an interplay between parenchymal and non-parenchymal cells. 2. There is increasing evidence for a role of the local renin-angiotensin system (RAS) in liver cell death, inflammatory response and liver regeneration. It has been shown that the local RAS plays an important regulatory role in a variety of tissues. In experimental hepatic fibrogenesis, the angiotensin AT(1) receptor (AT(1)R) blocker losartan has been shown to be able to attenuate transforming growth factor-b1 activity and collagen gene expression. 3. In the present study, using a D-galactosamine (GalN)-induced liver failure rat, AT(1)R were localized around the centrilobular region, which was not evident in normal liver. Blood tests showed an elevation of total bilirubin and alanine aminotransferase. Furthermore, there was an increase in tissue-specific inhibitor of metalloproteinase (TIMP)-1 protein in the liver. Losartan treatment was able to reduce all these parameters. Levels of TIMP-1 protein were reduced by 1.5- and 1.56-fold on Days 1 and 3, respectively (both P < 0.05), in the losartan-treated group relative to the GalN-treated group. The survival rate of the losartan-treated group was significantly higher than that of the GalN-treated group (5 day survival 85 vs 42.5%, respectively; P < 0.05). 4. In conclusion, the AT(1)R blocker losartan suppresses GalN-induced liver injury. This may indicate that AT(1)R blockers may have therapeutic potential in the treatment of acute liver injury.
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PMID:Effect of angiotensin AT1 receptor antagonist on D-galactosamine-induced acute liver injury. 1771 83

The atrial natriuretic peptide (ANP) are used as the acute heart failure treatment in clinical and reported the suppression of fibrosis in the heart, lung recently. The aim of this study was to analyze the suppressive effect of liver fibrosis about ANP. In vitro, rat hepatic stellate cell line (HSC-T6) were treated with ANP. In vivo, Wister rats were injected with dimethylnitrosamine (DMN) twice a week via intra-peritoneal for 4 weeks. ANP group was given by continuance intravenous dosage system used 24h infusion pump for 3 weeks after 1 week of DMN administration. In vitro, ANP suppressed alpha-SMA expression and was inhibited the growth of HSC, and reduced the expression of type 1 procollagen, TIMP-1, -2 expression. In vivo, The ANP group showed lower serum AST, ALT, HA level. Liver fibrosis was suppressed by ANP. ANP also decreased gene expression of type 1 procollagen, TIMP-1, -2 and alpha-SMA, TGF-beta1 expression. Our results showed that continuous ANP infusion has the specific capacity of inhibiting HSC activation and protecting hepatocytes and the useful capacity to suppress the liver fibrosis.
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PMID:Continuos intravenous infusion of atrial natriuretic peptide (ANP) prevented liver fibrosis in rat. 1899 92

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

Activation of hepatic stellate cells (HSCs) plays a crucial role in liver fibrogenesis. armepavine (Arm, C19H23O3N), an active compound from Nelumbo nucifera, has been shown to exert immunosuppressive effects on T lymphocytes and on lupus nephritic mice. The aim of this study was to investigate whether Arm could exert anti-hepatic fibrogenic effects in vitro and in vivo. A cell line of rat HSCs (HSC-T6) was stimulated with tumor necrosis factor-alpha (TNF-alpha) or lipopolysaccharide (LPS) to evaluate the inhibitory effects of Arm. An in vivo therapeutic study was conducted in bile duct-ligated (BDL) rats. BDL rats were given Arm (3 or 10 mg/kg) by gavage twice daily for 3 weeks starting from the onset of BDL. Liver sections were taken for fibrosis scoring, immuno-fluorescence staining and quantitative real-time mRNA measurements. In vitro, Arm (1-10 microM) concentration-dependently attenuated TNF-alpha- and LPS-stimulated alpha-SMA protein expression and AP-1 activation by HSC-T6 cells without adverse cytotoxicity. Arm also suppressed TNF-alpha-induced collagen collagen deposition, NFkappaB activation and MAPK (p38, ERK1/2, and JNK) phosphorylations. In vivo, Arm treatment significantly reduced plasma AST and ALT levels, hepatic alpha-SMA expression and collagen contents, and fibrosis scores of BDL rats as compared with vehicle treatment. Moreover, Arm attenuated the mRNA expression levels of col 1alpha2, TGF-beta1, TIMP-1, ICAM-1, iNOS, and IL-6 genes, but up-regulated metallothionein genes. Our study results showed that Arm exerted both in vitro and in vivo antifibrotic effects in rats, possibly through anti-NF-kappaB activation pathways.
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PMID:Inhibitory effects of armepavine against hepatic fibrosis in rats. 1972 40


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