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)

Anadromous arctic char (Salvelinus alpinus) undertake short feeding migrations to seawater every summer and accumulate lipids, while the rest of the year is spent in fresh water where the accumulated lipid reserves are mobilized. We tested the hypothesis that winter fasting and the associated polychlorinated biphenyls' (PCBs) redistribution from lipid depots to critical tissues impair the liver metabolic capacity in these animals. Char were administered Aroclor 1254 (0, 1, 10, and 100 mg/kg body mass) orally and maintained for 4 months without feeding to mimic seasonal winter fasting, while fed groups (0 and 100 mg Aroclor 1254/kg) were maintained for comparison. A clear dose-related increase in PCB accumulation and cytochrome P4501A (CYP1A) protein content was observed in the livers of fasted fish. This PCB concentration and CYP1A response with the high dose of Aroclor were 1.5-fold and 3-fold greater in the fasted than in the fed fish, respectively. In fed fish, PCB exposure lowered liver glycogen content, whereas none of the other metabolic indicators were significantly affected. In fasted fish, PCB exposure depressed liver glycogen content and activities of glucose-6-phosphate dehydrogenase, alanine aminotransferase, lactate dehydrogenase, and phosphoenolpyruvate carboxykinase and elevated 3-hydroxyacylcoA dehydrogenase activity and glucocorticoid receptor protein expression. There were no significant impacts of PCB on heat shock protein 70 (hsp70) and hsp90 contents in either fed or fasted fish. Collectively, our study demonstrates that winter emaciation associated with the anadromous lifestyle predisposes arctic char to PCB impact on hepatic metabolism including disruption of the adaptive metabolic responses to extended fasting.
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PMID:Fasting augments PCB impact on liver metabolism in anadromous arctic char. 1653 58

Propolis, a natural beehive product has been known for centuries for a variety of beneficial traditional medicinal properties. The present study was conducted to ascertain the antineoplastic potential of propolis along with paclitaxel against experimental mammary carcinogenesis. Female Sprague Dawley rats at 55 days of age were treated with dimethylbenz(a)anthracene to induce breast cancer. Paclitaxel at a dose of 33 mg/kg body mass intraperitoneally and propolis 50 mg/kg body weight orally was administered to the experimental animals, immediately after the carcinogen treatment and continued until the termination of the study. At the end of the treatment activities of phase I and II xenobiotic metabolizing enzymes and liver marker enzymes were measured. A significant increase in carcinogen activating enzymes, cytochrome P(450), cytochrome b(5) and NADPH cytochrome C reductase with concomitant decrease in phase II enzymes, glutathione transferase and UDP-glucuronyl transferase were observed in animals with mammary cancer. Furthermore there was a significant decrease in alanine aminotransferase, aspartate aminotransferase with a sharp increase in alkaline phosphatase, acid phosphatase and 5' nucleotidase. Propolis treatment caused the activity of these enzymes return to almost normal control levels, indicating the protective effect of propolis against dimethyl benz(a) anthracene induced carcinogenesis. On the basis of the observed results propolis can be considered a promising chemotherapeutic agent and can be administered as an adjuvant with paclitaxel chemotherapy.
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PMID:Therapeutic effect of propolis and paclitaxel on hepatic phase I and II enzymes and marker enzymes in dimethylbenz(a)anthracene-induced breast cancer in female rats. 1672 Jan 5

The present study investigates the hepatoprotective effect of fenugreek seed polyphenolic extract (FPEt) against ethanol-induced hepatic injury and apoptosis in rats. Chronic ethanol administration (6 g/kg/day x 60 days) caused liver damage that was manifested by the elevation of markers of liver dysfunction--aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin and gamma-glutamyl transferase (GGT) in plasma and reduction in liver glycogen. The effects on alcohol metabolizing enzymes such as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were studied and found to be altered in the alcohol-treated group. Ethanol administration resulted in adaptive induction of the activities of cytochrome p450 (cyt-p-450) and cytochrome-b5 (cyt-b5) and reduction in cytochrome-c-reductase (cyt-c-red) and glutathione-S-tranferase (GST), a phase II enzyme. Further, ethanol reduced the viability of isolated hepatocytes (ex vivo) as assessed by the trypan blue exclusion test and increased hepatocyte apoptosis as assessed by propidium iodide staining (PI). Treatment with FPEt restored the levels of markers of liver injury and mitigated the alterations in alcohol metabolizing and detoxification enzymes and the electron transport component cytochrome-c reductase. Increased hepatocyte viability and reduced apoptotic nuclei were observed in FPEt-treated rats. These findings demonstrate that FPEt acts as a protective agent against ethanol-induced abnormalities in the liver. The effects of FPEt are comparable with those of a known hepatoprotective agent, silymarin.
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PMID:Fenugreek (Trigonella foenum graecum) seed polyphenols protect liver from alcohol toxicity: a role on hepatic detoxification system and apoptosis. 1748 88

Tipranavir is a recently approved nonpeptidic protease inhibitor specifically developed for the management of human immunodeficiency virus (HIV) infection in treatment-experienced patients with protease inhibitor-resistant infection. It is active against a wide range of drug-resistant laboratory- and patient-derived isolates. Tipranavir requires pharmacokinetic boosting by ritonavir (200 mg) to achieve therapeutic levels with twice-daily dosing and must be administered with food for optimal absorption. It is a potent protease inhibitor with a unique drug-resistance profile that offers advantages in the management of cases of multidrug-resistant HIV infection. Tipranavir (in combination with ritonavir) is both an inhibitor and inducer of cytochrome p450, with significant potential for drug-drug interactions, and therefore, it must be used cautiously when administered to patients who are receiving other drugs. Evolution of drug resistance after treatment failure with tipranavir is complex and is not yet fully understood. There is limited overlap in the resistance mutations that predict response to tipranavir and another new protease inhibitor, darunavir, which is active against drug-resistant isolates. Tipranavir is associated with elevations in alanine aminotransferase and aspartate aminotransferase levels, as well as elevated cholesterol and triglyceride levels, and can cause the typical gastrointestinal adverse effects associated with all protease inhibitors.
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PMID:Tipranavir: a new option for the treatment of drug-resistant HIV infection. 1771 62

Massive hepatectomy associated with infection induces liver dysfunction, or even multiple organ failure and death. Glycyrrhizin has been shown to exhibit anti-oxidant and anti-inflammatory activities. The aim of the present study was to investigate whether glycyrrhizin could attenuate endotoxin-induced acute liver injury after partial hepatectomy. Male Wistar rats (6 to 8 weeks old, weighing 200-250 g) were randomly assigned to three groups of 24 rats each: sham, saline and glycyrrhizin. Rats were injected intravenously with lipopolysaccharide (LPS) 24 h after 70% hepatectomy. Glycyrrhizin, pre-administered three times with 24 h intervals 48 h before hepatectomy, prolonged the survival of rats submitted to partial hepatectomy and LPS injection, compared with saline controls. Glycyrrhizin was shown to attenuate histological hepatic changes and significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase, at all the indicated times (6 rats from each were sacrificed 1, 3, 6, and 9 h after LPS injection), compared with saline controls. Glycyrrhizin also significantly inhibited hepatocyte apoptosis by down-regulating the expression of caspase-3 and inhibiting the release of cytochrome C from mitochondria into the cytoplasm. The anti-inflammatory activity of glycyrrhizin may rely on the inhibition of release of tumor necrosis factor-a, myeloperoxidase activity, and translocation of nuclear factor-kappa B into the nuclei. Glycyrrhizin also up-regulated the expression of proliferating cell nuclear antigen, implying that it might be able to promote regeneration of livers harmed by LPS. In summary, glycyrrhizin may represent a potent drug protecting the liver against endotoxin-induced injury, especially after massive hepatectomy.
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PMID:Glycyrrhizin attenuates endotoxin- induced acute liver injury after partial hepatectomy in rats. 1799 67

To assess the effect of gadolinium (Gd) on the expression of several forms of cytochrome P450 (P450s) and antioxidant enzymes, we treated rats with gadolinium chloride (25 mg as Gd/kg body weight) 4 h after styrene (a multiple P450 inducer) treatment (600 mg/kg). Gd treatment significantly suppressed styrene-inducible cytochrome P4502B1 (CYP2B1), CYP2B2, CYP2E1, and CYP3A2 mRNA expressions to 48.6%, 69.8%, 61.1%, and 38.5%, accompanying with the reduction of proteins expression to 1.42%, 31.2%, 21.1% and 21.1%, respectively, compared with styrene alone treatment. Gd suppressed styrene-inducible CYP1A2 expression, but only at the protein level. On the other hand, styrene treatment caused a decrease in reduced form of glutathione (GSH), as well as increases in lipid peroxide and serum ALT and AST activities, suggesting the occurrence of hepatic damage probably due to styrene-induced oxidative stress in rat liver. Post-treatment of Gd attenuated this styrene-caused hepatic damage. Moreover, mRNA expressions of cellular antioxidant enzymes such as catalase, CuZn-superoxide dismutase (CuZnSOD) and glutathione peroxidase (GPX) were hardly changed by styrene and/or Gd treatment. In summary, Gd suppressed styrene-inducible expression of not only CYP2B1 but also several forms of P450 at both the mRNA and protein levels, along with attenuation of styrene-caused liver damage. These findings suggested that Gd is a chemo-preventive agent against hepatic damage caused by xenobiotics requiring biotransformation.
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PMID:Gadolinium chloride suppresses styrene-induced cytochrome P450s expression in rat liver. 1820 23

The hepatoprotective efficacy of irradiated hyaluronic acid (HA) on acetaminophen (APAP) induced acute hepatotoxicity was investigated. BALB/c mice (4-6 weeks of age) were pretreated with unirradiated HA (UIHA), 5 and 50 kGy gamma irradiated HA (GIHA) for 14 days and were dosed APAP (500 mg/kg b.wt). After 9h of APAP dosing animals were euthanized. The degree of acute hepatotoxicity was measured by aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The expression of interferon-gamma (IFN-gamma) in serum and alpha-and mu-class of gluthathione-S-transferase (GSTs), CYP 2E1 class of cytochrome monooxygenase and glutathione (GSH) in liver were quantified. Histological evaluation was done by Hematoxiylin and Eiosin staining, Periodic acid schiffs staining, Manson trichrome staining and histological scorings were done. The degree of acute hepatotoxicity was markedly lower in UIHA and 5 kGy than in 50 kGy GIHA pretreated group and there was negligible difference between 5 and 50 kGy GIHA pretreated group. The expression of interferon-gamma (IFN-gamma) was significantly (P<0.05) suppressed in 5 and 50 kGy GIHA pretreated group. Histological scorings showed a significant protection of liver in UIHA and 5 kGy GIHA pretreated mice. Expression of alpha class GSTs was significantly increased in 5 and 50 kGy GIHA pretreated group. To conclude suppression of IFN-gamma and increase in alpha-class GSTs expression may exert a protective role in acute hepatotoxicity of APAP and 5 kGy GIHA showed comparable protective effect to that of UIHA.
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PMID:Effect of gamma irradiated hyaluronic acid on acetaminophen induced acute hepatotoxicity. 1823 25

Renal ischemia/reperfusion (I/R) occurs in many clinical scenarios, including trauma, elective surgery, and transplantation. Events initiated by this process can lead to inflammation in the kidneys, culminating in local injury as well as distant organ dysfunction. The objectives of this study were to investigate the changes in the functions of the liver and the regulation of gene expression of cytochrome P450 (CYP) isozymes after renal I/R. Hepatoxocity was assessed by serum alanine aminotransferase (sALT), serum aspartate aminotransferase (sAST) and liver glutathione-S-transferase (GST) activities, liver glutathione (GSH) level, and histopathological examination. Hepatic cytochrome P4503A1 (CYP3A1) and cytochrome P4502E1 (CYP2E1) activities were measured by erythromycin N-demethylase (ERD) and aniline hydroxylase (ANH) activities, respectively. CYP3A1 and CYP2E1 mRNA expression was determined by RT-PCR. Results showed that activities of sALT and sAST were significantly increased, while hepatic CYP3A1and CYP2E1 activities as well as their respective mRNA levels were significantly decreased after renal I/R. Moreover, hepatic tissue congestion, degeneration, and local necrosis were observed in rats after 1, 4, and 8h renal reperfusion following 2h renal ischemia. In conclusion, the present study suggests that renal I/R can cause hepatotoxicity and gene expression down-regulation of CYP isozymes in rats.
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PMID:Hepatotoxicity and gene expression down-regulation of CYP isozymes caused by renal ischemia/reperfusion in the rat. 1923 Jun 30

Oxidative stress and inflammation contributed to the propagation of acute liver injury (ALI). The present study was undertaken to determine whether D-galactosamine (D-GalN) induces ALI via the mitochondrial apoptosis- and proinflammatory cytokine-signaling pathways, and possible mechanism(s) by which green tea (GT) extract modulates the apoptotic and proinflammatory signaling in rat. D-GalN induced hepatic hypoxia/hypoperfusion and triggered reactive oxygen species (ROS) production from affected hepatocytes, infiltrated leukocytes, and activated Kupffer cells. D-GalN evoked cytosolic Bax and mitochondrial cytochrome C translocation and activated proinflammatory nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) translocation, contributing to the increase of intercellular adhesion molecule-1 expression, terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL)-positive hepatocytes, multiple plasma cytokines and chemokines release, and alanine aminotransferase (ALT) activity. An altered biliary secretion profile of several acute phase proteins directly indicates oxidative stress affecting intracellular trafficking in the hepatocyte. GT pretreatment attenuated ROS production, mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, plasma ALT and cytokines levels, biliary acute phase proteins secretion and hepatic pathology by the enhancement of anti-apoptotic mechanisms. In conclusion, D-GalN induced ALI via hypoxia/hypoperfusion-enhanced mitochondrial apoptosis- and proinflammatory cytokine-signaling pathway, contributing to oxidative stress and inflammation in the liver. GT can counteract the D-GalN-induced ALI via the attenuation of apoptotic and proinflammatory signaling by the upregulation of anti-apoptotic mechanism.
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PMID:Green tea extract supplement reduces D-galactosamine-induced acute liver injury by inhibition of apoptotic and proinflammatory signaling. 1931 20

Acacia confusa Merr. (Leguminosae), a species native to Taiwan, is widely distributed on the hills and lowlands of Taiwan, and has been traditionally used as a medicine. The hepatoprotective effects of A. confusa bark extract (ACBE) and its active constituent gallic acid were evaluated against carbon tetrachloride (CCl(4))-induced hepatotoxicity in rats. CCl(4)-induced hepatic pathological damage and significantly increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malondialdehyde (MDA) in plasma, and cytochrome P4502E1 (CYP2E1) protein expression in hepatic samples, and decreased the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) in erythrocytes. Treatment with ACBE, gallic acid or silymarin could decrease significantly the AST, ALT, and MDA levels in plasma, and CYP2E1 expression in liver tissues, and increase the activities of SOD and GPX in erythrocyte when compared with CCl(4)-treated group. Liver histopathology also showed that ACBE, gallic acid or silymarin could significantly reduce the incidence of liver lesions induced by CCl(4). These results suggested that the ACBE and gallic acid exhibit potent hepatoprotection against CCl(4)-induced liver damages in rats, and the hepatoprotective effects of ACBE and gallic acid may be due to the modulation of antioxidant enzymes activities and inhibition of lipid peroxidation and CYP2E1 activation.
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PMID:Protective effect of Acacia confusa bark extract and its active compound gallic acid against carbon tetrachloride-induced chronic liver injury in rats. 1932 82


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