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)

Pentoxifylline (PTX) has been shown to protect the liver against normothermic ischemia-reperfusion (I-R) injury. The aims of this study were to investigate the action of PTX on tumor necrosis factor alpha (TNFalpha) gene transcription following normothermic liver I-R as well as to evaluate the resulting effects on liver function and survival. A segmental normothermic liver ischemia was induced for 90 minutes. Rats were divided into three groups: group 1, control, Ringer lactate administration; group 2, PTX treatment; group 3, sham-operated control rats. PTX (50 mg/kg) was injected intravenously 30 minutes before induction of ischemia and 30 minutes before reperfusion. The nonischemic liver lobes were resected at the end of ischemia. Survival rates were compared and serum activities of TNFalpha, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were measured. Liver histology was assessed 6 hours after reperfusion. Liver TNFalpha mRNA was assessed by polymerase chain reaction amplification at different times after reperfusion. PTX treatment significantly decreased serum activities of TNFalpha and inhibited liver expression of TNFalpha mRNA. The extent of liver necrosis and serum levels of liver enzymes were significantly decreased by PTX treatment, resulting in a significant increase in 7-day survival compared with nontreated control rats. In conclusion, PTX inhibits liver TNFalpha gene transcription, decreases serum TNFalpha levels, and reduces liver injury following normothermic I-R.
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PMID:Inhibition of tumor necrosis factor alpha gene transcription by pentoxifylline reduces normothermic liver ischemia-reperfusion injury in rats. 1769 5

In the present study, latex of Calotropis procera possessing potent antioxidant and anti-inflammatory properties was evaluated for its hepatoprotective effect against carbon tetrachloride (CCl(4)) induced hepatotoxicity in rats. Subcutaneous injection of CCl(4,) administered twice a week, produced a marked elevation in the serum levels of aspartate transaminase (AST), alanine transaminase (ALT) and tumor necrosis factor alpha (TNF-alpha). Histological analysis of the liver of these rats revealed marked necro-inflammatory changes that were associated with increase in the levels of TBARS, PGE(2) and catalase and decrease in the levels of glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Daily oral administration of aqueous suspension of dried latex (DL) of Calotropis procera at 5, 50 and 100mg/kg doses produced a dose-dependent reduction in the serum levels of liver enzymes and inflammatory mediators and attenuated the necro-inflammatory changes in the liver. The DL treatment also normalized various biochemical parameters of oxidative stress. Our study shows that the antioxidant and anti-inflammatory effects of DL and silymarin were comparable and suggests that DL could be used as a hepatoprotective agent.
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PMID:Calotropis procera latex affords protection against carbon tetrachloride induced hepatotoxicity in rats. 1770 84

The present study was undertaken to investigate the protective effect and possible mechanism of aqueous extract from Phyllanthus amarus Schum. et. Thonn. (PA) on ethanol-induced rat hepatic injury. In the in vitro study, PA (1-4 mg/ml) increased %MTT reduction assay and decreased the release of transaminases (AST and ALT) in rat primary cultured hepatocytes being treated with ethanol. Hepatotoxic parameters studied in vivo included serum transaminases (AST and ALT), serum triglyceride (STG), hepatic triglyceride (HTG), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta), together with histopathological examination. In acute toxicity study, single dose of PA (25, 50 and 75 mg/kg, p.o.) or SL (silymarin, a reference hepatoprotective agent, 5 mg/kg), 24h before ethanol (5 g/kg, p.o.) lowered the ethanol-induced levels of transaminases (AST and/or ALT). The 75 mg/kg PA dose gave the best result similar to SL. Treatment of rats with PA (75 mg/(kg day), p.o.) or SL (5 g/(kg day), p.o.) for 7 days after 21 days with ethanol (4 g/(kg day), p.o.) enhanced liver cell recovery by bringing the levels of AST, ALT, HTG and TNF-alpha back to normal. Histopathological observations confirmed the beneficial roles of PA and SL against ethanol-induced liver injury in rats. Possible mechanism may involve their antioxidant activity.
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PMID:Hepatoprotective activity of Phyllanthus amarus Schum. et. Thonn. extract in ethanol treated rats: in vitro and in vivo studies. 1787 Feb 64

Hepatic oxidative stress plays a critical role in metabolic forms of steatohepatitis. Phyllanthus urinaria, an herbal medicine, has been reported to have potential antioxidant properties. We tested the effects of P. urinaria on nutritional steatohepatitis both in vitro and in vivo. Immortalized normal hepatocytes (AML-12) or primary hepatocytes were exposed to control, the methionine-and-choline-deficient (MCD) culture medium, in the presence or absence of P. urinaria for 24 hours. Hepatocyte triglyceride, release of alanine aminotransferase, lipoperoxides, and reactive oxygen species production were determined. Age-matched C57BL/6 and db/db mice were fed control or MCD diet for 10 days with or without P. urinaria. Hepatic steatosis, necroinflammation, triglycerides, and lipid peroxide levels were determined. Hepatic expression of inflammatory factors and lipid regulatory mediators were assayed. P. urinaria reduced steatosis and alanine aminotransferase (ALT) levels in culture of hepatocytes in a dose-dependent manner. Phyllanthus prevented MCD-induced hepatic fat accumulation and steatohepatitis in mice. This effect was associated with repressed levels of hepatic lipid peroxides, reduced expression of cytochrome P450-2E1, pro-inflammatory tumor necrosis factor alpha, interleukin-6, dampened activation of inflammatory c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-kappaB), increased expression of lipolytic cytochrome P450 (Cyp4a10), and suppressed transcriptional activity of lipogenic CCAAT/enhancer binding protein beta (C/EBPbeta). Hepatic acyl co-enzyme A oxidase that regulated hepatic beta-oxidation of fatty acid and other lipid regulators were not affected by P. urinaria. In conclusion, P. urinaria effectively alleviated the steatohepatitis induced by the MCD, probably through dampening oxidative stress, ameliorating inflammation, and decreasing lipid accumulation.
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PMID:Phyllanthus urinaria ameliorates the severity of nutritional steatohepatitis both in vitro and in vivo. 1815 36

Mao is one component of various traditional herbal medicines. We examined the effects of Mao on an acute liver failure model treated with d-galactosamine (GalN) and lipopolysaccharide (LPS). The lethality of mice administrated Mao with GalN/LPS was significantly decreased compared with that in mice without Mao. Hepatic apoptosis and inflammatory cell infiltration were slight in Mao-treated mice. Serum alanine aminotransferase (ALT) and total bilirubin (T.Bil) activity, tumor necrosis factor alpha (TNF-alpha) levels and caspase 8, 9, and 3 activity in the liver were significantly lower in mice administrated Mao. But, Serum interleukin-6 (IL-6), IL-10 levels and signal transducers and activators of transcription 3 (STAT3) activity in the liver were significantly higher in mice administrated Mao. To investigate the effect of STAT3, we used AG490, which selectively inhibits the activation of Janus kinase (JAK) family tyrosine kinase and inhibits the constitutive activation of STAT3. There was significant aggravation in hepatic apoptosis treated with Mao and AG490 compared with Mao alone. In conclusions, Mao significantly suppressed hepatic apoptosis by inhibition of TNF-alpha production and caspase activity. Furthermore, it is also suggested that Mao, which activates STAT3 induced by IL-6, may be a useful therapeutic tool for fulminant hepatic failure.
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PMID:Mao (Ephedra sinica Stapf) protects against D-galactosamine and lipopolysaccharide-induced hepatic failure. 1821 21

Oxidative stress, cytokine over expression and Kupffer cell activation are well-documented pathological factors in the development of alcoholic liver disease. Bicyclol is a novel synthetic anti-hepatitis drug with anti-oxidative and anti-inflammatory property. The present study was to investigate the effect of bicyclol on acute alcohol-induced liver injury and related mechanisms in mice. Bicyclol (200, 300 mg/kg) was given to mice by gavage for three times. Alcohol (6 g/kg) was administered orally 1 h after the last dose of bicyclol. All animals were sacrificed at different time points after alcohol administration. Liver injury was evaluated by biochemical and histopathological examination. Lipid peroxidation and the activity of antioxidants were measured by spectrophotometric method. Expression of cytokines and CD14 were determined by enzyme-linked immunosorbent assay, reverse transcriptional-polymerase chain reaction and immunohistochemical staining. As a result, bicyclol pretreatment significantly protected against acute alcohol-induced liver injury as evidenced by the decrease of elevated serum alanine aminotransferase and hepatic triglyceride, and the attenuation of histopathological changes in mice. In addition, bicyclol remarkably alleviated the formation of thiobarbituric acid-reactive substance and restored impaired antioxidants, including glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Over-expression of cytokines, such as tumor necrosis factor alpha and interleukin 1beta, elevated plasma endotoxin level, and up-regulation of CD14 were also suppressed by bicyclol in alcohol-intoxicated mice. The protective effect of bicyclol on alcohol-induced hepatotoxicity was mainly due to its ability to attenuate oxidative stress, suppress the cytokine expression at both protein and gene level, and inhibit the activation of Kupffer cells by decreasing plasma endotoxin level and CD14 expression.
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PMID:Protective effect of bicyclol on acute alcohol-induced liver injury in mice. 1837 52

Acetaminophen (APAP) elicits hepatotoxicity via multifactorial pathways, including increased apoptosis, cyclooxygenase (Cox-2) generation, reactive metabolite release, and glutathione (GSH) depletion. We previously showed that mice that consumed different antioxidants in their diets were protected against APAP-induced hepatotoxicity. We therefore further investigated the mechanisms by which green-tea polyphenols (GrTP) protect against APAP-induced hepatic damage. Mice were administered a diet supplemented with GrTP or vehicle for 5 consecutive days followed by intraperitoneal (IP) injection of a toxic dose of APAP or sham. APAP administration upregulated Cox-2 and B-cell lymphoma-2 (Bcl-2) production and had an effect, albeit minor, on Cox-1 and Fas expression in hepatic tissue. GrTP supplementation normalized APAP induced Cox-2 expression and Bcl-2 activation (P < 0.01), as evidenced by immunohistochemistry and Western blot analyses. Similarly, APAP administration elicited marked depletion (99%) in hepatic reduced GSH (rGSH) and endogenous S-adenosylmethionine (SAMe) concentrations (twofold) when compared with sham. APAP also caused severe centrilobular apoptosis and necrosis accompanied by leukocyte infiltration and marked elevations in the hepatic enzyme, alanine aminotransferase (ALT) released from damaged hepatocytes, and cytokine tumor necrosis factor alpha (TNF-alpha). GrTP improved hepatic histopathology (P < 0.01) and attenuated ALT activity (P < 0.05) and the depletion of rGSH (P < 0.05). In conclusion, GrTP supplementation attenuated hepatotoxicity by normalizing Cox-2 and Bcl-2 activation, suggesting a potential use for GrTP in treatng APAP toxicity.
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PMID:Green-tea polyphenols downregulate cyclooxygenase and Bcl-2 activity in acetaminophen-induced hepatotoxicity. 1837 99

Severe sepsis remains a leading cause of death and disability because of less effective therapy available for this disease. A complex interplay between the inflammatory factors and the coagulation pathways seems to be the fundamental mechanisms for the pathogenesis of sepsis. Here we report that recombinant fibrinogenase II (rF II) from Agkistrodon acutus plasmin-independently degraded the thrombi, and inhibited inflammatory responses by direct and specific degradation of tumor necrosis factor alpha (TNF-alpha) induced by lipopolysaccharide (LPS) without showing proteolytic activities on interleukin-1 (IL-1), cluster of differentiation 68 (CD68) and some other serum proteins. We also report that rF II effectively protected against LPS induced sepsis in a rabbit model. Administration of rF II reduced hepatic and renal damage, decreased the levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN), and increased survival rate in LPS-induced sepsis rabbits. We further confirmed the rescue effect of rF II on severe sepsis in rat caecal ligation and puncture (CLP) model. Our findings suggest that rF II could effectively protect against sepsis via direct degradation of microthrombi and inflammatory factor TNF-alpha as well as provide a novel strategy to develop a single proteinase molecule for targeting the main pathological processes of this disease.
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PMID:Recombinant fibrinogenase from Agkistrodon acutus venom protects against sepsis via direct degradation of fibrin and TNF-alpha. 1863 54

Mercuric chloride (HgCl(2)) is a widespread environmental toxin that affects mainly liver and kidney. The present study has been carried out to investigate the protective action of a protein (the CI protein) isolated from the herb, Cajanus indicus Spreng against HgCl(2) induced renal and hepatic toxicities in mice. Intraperitoneal administration of HgCl(2) at a dose of 5 mg/kg body weight for 1 d significantly reduced the activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Moreover, it also depleted the glutathione to oxidized glutathione (GSH/GSSG) ratio. In addition, HgCl(2) increased the activities of serum marker enzymes (namely, glutamate pyruvate transaminase, GPT and alkaline phosphatase, ALP), creatinine, blood urea nitrogen and serum tumor necrosis factor alpha (TNF-alpha) level along with hepatic and renal lipid peroxidation. Besides, application of HgCl(2) to hepatocytes increased reactive oxygen species production and reduced the total antioxidant activity of the treated hepatocytes. Treatment with the CI protein intraperitoneally at a dose of 2 mg/kg body weight before or after HgCl(2) administration showed that it could scavenge free radicals in vitro and protect the alterations of the antioxidant molecules and the other parameters used in this particular study. Histological studies also revealed a milder lesion in kidney and liver samples of the CI protein treated mice compared to mice treated with HgCl(2) alone. Effects of a known antioxidant N-acetylcysteine have been used to compare its action to that of the CI protein.
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PMID:A protein from Cajanus indicus Spreng protects liver and kidney against mercuric chloride-induced oxidative stress. 1875 54

The purpose of this study was to investigate possible beneficial effects of morin on CCl(4)-induced acute hepatotoxicity in rats. Rats received a single dose of CCl(4) (150 microL/100 g 1:1 in corn oil). Morin treatment (20 mg/kg) was given at 48, 24, and 2 h before CCl(4) administration. CCl(4) challenge elevated serum alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) levels, but these effects were prevented by the pretreatment of rats with morin. To identify the mechanism of protective activity of morin in CCl(4)-induced hepatotoxicity in rats, we investigated expressions of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and inducible nitric oxide (iNOS). The expressions of TNF-alpha, IL-1beta, IL-6, and iNOS were increased by CCl(4) treatment and increased expressions of those were decreased by morin. These findings suggest that morin prevents acute liver damage by inhibiting the production of TNF-alpha, IL-1beta, IL-6, and iNOS.
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PMID:Morin protects acute liver damage by carbon tetrachloride (CCl(4)) in rat. 1880 59


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