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  1. Elevated Liver Enzymes

    Science.gov (United States)

    Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

  2. Peroxisomal enzymes in the liver of rats with experimental diabetes mellitus type 2.

    Science.gov (United States)

    Turecký, L; Kupčová, V; Uhlíková, E; Mojto, V

    2014-01-01

    Diabetes mellitus is relatively frequently associated with fatty liver disease. Increased oxidative stress probably plays an important role in the development of this hepatopathy. One of possible sources of reactive oxygen species in liver is peroxisomal system. There are several reports about changes of peroxisomal enzymes in experimental diabetes, mainly enzymes of fatty acid oxidation. The aim of our study was to investigate the possible changes of activities of liver peroxisomal enzymes, other than enzymes of beta-oxidation, in experimental diabetes mellitus type 2. Biochemical changes in liver of experimental animals suggest the presence of liver steatosis. The changes of serum parameters in experimental group are similar to changes in serum of patients with non-alcoholic fatty liver disease. We have shown that diabetes mellitus influenced peroxisomal enzymes by the different way. Despite of well-known induction of peroxisomal beta-oxidation, the activities of catalase, aminoacid oxidase and NADH-cytochrome b(5) reductase were not significantly changed and the activities of glycolate oxidase and NADP-isocitrate dehydrogenase were significantly decreased. The effect of diabetes on liver peroxisomes is probably due to the increased supply of fatty acids to liver in diabetic state and also due to increased oxidative stress. The changes of metabolic activity of peroxisomal compartment may participate on the development of diabetic hepatopathy.

  3. Elevated liver enzymes in women with a family history of diabetes.

    Science.gov (United States)

    Inoue, Kazuo; Matsumoto, Masatoshi; Miyoshi, Yuji; Kobayashi, Yasuki

    2008-03-01

    Both elevated liver enzymes and a family history of diabetes mellitus (FHDM) are independent risk factors for type 2 diabetes. This study evaluates the epidemiological association between elevated liver enzymes and FHDM. Subjects included 3512 women workers without diabetes, hepatitis, a smoking habit, or a history of alcohol intake. Blood samples and personal data were collected from all subjects. Subjects with FHDM had a higher mean body mass index (BMI: 23.9kg/m(2) vs. 23.4kg/m(2); p=0.003). Laboratory testing also revealed higher mean fasting plasma glucose (FPG: 5.67mmol/L vs. 5.22mmol/L; penzymes were associated with FHDM. In particular, elevated GGT was related to FHDM, independent of the other variables. Elevated liver enzymes, probably due to fat deposition in the liver, may play a role in increasing the risk of diabetes in individuals with FHDM.

  4. Evaluation of liver marker enzymes and biochemical indices of ...

    African Journals Online (AJOL)

    Liver marker enzymes, total protein, amylase and glucose were evaluated in alloxan-induced diabetic wistar rats treated with aqueous extract of Pennisetum purpureum. The liver marker enzymes evaluated were alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Sixteen wistar rats were grouped into ...

  5. Ethosuximide: liver enzyme induction and D-glucaric acid excretion.

    Science.gov (United States)

    Gilbert, J C; Scott, A K; Galloway, D B; Petrie, J C

    1974-06-01

    1 A study has been carried out to determine if ethosuximide induces liver enzymes. 2 Ethosuximide did not affect the urinary excretion of D-glucaric acid by healthy adult subjects nor was the mean daily D-glucaric acid excretion of three epileptic children on long term ethosuximide therapy different from that of three matched controls. 3 Ethosuximide (10 mg/kg or 50 mg/kg daily) did not influence D-glucaric acid excretion or liver microsomal protein and cytochrome P450 contents of guinea pigs but at a dose of 100 mg/kg daily in rats it increased liver microsomal protein and cytochrome P450 without altering D-glucaric acid excretion. 4 These results suggest that at anticonvulsant doses ethosuximide is unlikely to induce liver enzymes. The precise relationship between D-glucaric acid excretion and liver enzyme induction remains in doubt.

  6. Measurement of peroxisomal enzyme activities in the liver of brown trout (Salmo trutta, using spectrophotometric methods

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    Resende Albina D

    2003-03-01

    Full Text Available Abstract Background This study was aimed primarily at testing in the liver of brown trout (Salmo trutta spectrophotometric methods previously used to measure the activities of catalase and hydrogen peroxide producing oxidases in mammals. To evaluate the influence of temperature on the activities of those peroxisomal enzymes was the second objective. A third goal of this work was the study of enzyme distribution in crude cell fractions of brown trout liver. Results The assays revealed a linear increase in the activity of all peroxisomal enzymes as the temperature rose from 10° to 37°C. However, while the activities of hydrogen peroxide producing oxidases were strongly influenced by temperature, catalase activity was only slightly affected. A crude fraction enriched with peroxisomes was obtained by differential centrifugation of liver homogenates, and the contamination by other organelles was evaluated by the activities of marker enzymes for mitochondria (succinate dehydrogenase, lysosomes (aryl sulphatase and microsomes (NADPH cytochrome c reductase. For peroxisomal enzymes, the activities per mg of protein (specific activity in liver homogenates were strongly correlated with the activities per g of liver and with the total activities per liver. These correlations were not obtained with crude peroxisomal fractions. Conclusions The spectrophotometric protocols originally used to quantify the activity of mammalian peroxisomal enzymes can be successfully applied to the study of those enzymes in brown trout. Because the activity of all studied peroxisomal enzymes rose in a linear mode with temperature, their activities can be correctly measured between 10° and 37°C. Probably due to contamination by other organelles and losses of soluble matrix enzymes during homogenisation, enzyme activities in crude peroxisomal fractions do not correlate with the activities in liver homogenates. Thus, total homogenates will be used in future seasonal and

  7. Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver

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    G.B. Peres

    2014-06-01

    Full Text Available It has been previously shown that dextran sulfate administered to diabetic rats accumulates in the liver and kidney, and this could be due to a malfunction of the lysosomal digestive pathway. The aim of the present study was to evaluate the expression and activities of lysosomal enzymes that act upon proteins and sulfated polysaccharides in the livers of diabetic rats. Diabetes mellitus was induced by streptozotocin in 26 male Wistar rats (12 weeks old, while 26 age-matched controls received only vehicle. The livers were removed on either the 10th or the 30th day of the disease, weighed, and used to evaluate the activity, expression, and localization of lysosomal enzymes. A 50-60% decrease in the specific activities of cysteine proteases, especially cathepsin B, was observed in streptozotocin-induced diabetes mellitus. Expression (mRNA of cathepsins B and L was also decreased on the 10th, but not on the 30th day. Sulfatase decreased 30% on the 30th day, while glycosidases did not vary (or presented a transitory and slight decrease. There were no apparent changes in liver morphology, and immunohistochemistry revealed the presence of cathepsin B in hepatocyte granules. The decrease in sulfatase could be responsible for the dextran sulfate build-up in the diabetic liver, since the action of sulfatase precedes glycosidases in the digestive pathway of sulfated polysaccharides. Our findings suggest that the decreased activities of cathepsins resulted from decreased expression of their genes, and not from general lysosomal failure, because the levels of glycosidases were normal in the diabetic liver.

  8. Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver

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    Peres, G.B. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Bioquímica, São Paulo, SP, Brasil, Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Juliano, M.A. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Biofísica, São Paulo, SP, Brasil, Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Aguiar, J.A.K.; Michelacci, Y.M. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Bioquímica, São Paulo, SP, Brasil, Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2014-05-09

    It has been previously shown that dextran sulfate administered to diabetic rats accumulates in the liver and kidney, and this could be due to a malfunction of the lysosomal digestive pathway. The aim of the present study was to evaluate the expression and activities of lysosomal enzymes that act upon proteins and sulfated polysaccharides in the livers of diabetic rats. Diabetes mellitus was induced by streptozotocin in 26 male Wistar rats (12 weeks old), while 26 age-matched controls received only vehicle. The livers were removed on either the 10{sup th} or the 30{sup th} day of the disease, weighed, and used to evaluate the activity, expression, and localization of lysosomal enzymes. A 50-60% decrease in the specific activities of cysteine proteases, especially cathepsin B, was observed in streptozotocin-induced diabetes mellitus. Expression (mRNA) of cathepsins B and L was also decreased on the 10{sup th}, but not on the 30{sup th} day. Sulfatase decreased 30% on the 30{sup th} day, while glycosidases did not vary (or presented a transitory and slight decrease). There were no apparent changes in liver morphology, and immunohistochemistry revealed the presence of cathepsin B in hepatocyte granules. The decrease in sulfatase could be responsible for the dextran sulfate build-up in the diabetic liver, since the action of sulfatase precedes glycosidases in the digestive pathway of sulfated polysaccharides. Our findings suggest that the decreased activities of cathepsins resulted from decreased expression of their genes, and not from general lysosomal failure, because the levels of glycosidases were normal in the diabetic liver.

  9. Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver

    International Nuclear Information System (INIS)

    Peres, G.B.; Juliano, M.A.; Aguiar, J.A.K.; Michelacci, Y.M.

    2014-01-01

    It has been previously shown that dextran sulfate administered to diabetic rats accumulates in the liver and kidney, and this could be due to a malfunction of the lysosomal digestive pathway. The aim of the present study was to evaluate the expression and activities of lysosomal enzymes that act upon proteins and sulfated polysaccharides in the livers of diabetic rats. Diabetes mellitus was induced by streptozotocin in 26 male Wistar rats (12 weeks old), while 26 age-matched controls received only vehicle. The livers were removed on either the 10 th or the 30 th day of the disease, weighed, and used to evaluate the activity, expression, and localization of lysosomal enzymes. A 50-60% decrease in the specific activities of cysteine proteases, especially cathepsin B, was observed in streptozotocin-induced diabetes mellitus. Expression (mRNA) of cathepsins B and L was also decreased on the 10 th , but not on the 30 th day. Sulfatase decreased 30% on the 30 th day, while glycosidases did not vary (or presented a transitory and slight decrease). There were no apparent changes in liver morphology, and immunohistochemistry revealed the presence of cathepsin B in hepatocyte granules. The decrease in sulfatase could be responsible for the dextran sulfate build-up in the diabetic liver, since the action of sulfatase precedes glycosidases in the digestive pathway of sulfated polysaccharides. Our findings suggest that the decreased activities of cathepsins resulted from decreased expression of their genes, and not from general lysosomal failure, because the levels of glycosidases were normal in the diabetic liver

  10. Evaluating correlation between serum liver enzymes and toxocariasis: a case control study

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    Hosein Miladi

    2016-06-01

    Full Text Available Objective: To evaluate the prevalence of toxocariasis in individuals with the normal and abnormal level of liver enzymes. Methods: In this case-control study, the serum samples were collected in the individuals referred to diagnostic laboratories of Arak in Iran. A total of 144 sera with abnormal level of liver enzymes were selected as cases and the same numbers of sera with the normal level of liver enzymes also were selected as controls. The sera were examined for anti-Toxocara IgG. Results: Twelve (4.2% sera contained anti-Toxocara antibody and all of them were in the case group. Although the mean of all liver enzymes was significantly different in the two groups (P < 0.05, statistical test showed no relationship between the level of liver enzymes and toxocariasis. Conclusions: It was concluded that the liver enzyme alteration is not the valid indicator for predicting toxocariasis. Because the kind of liver dysfunction, that is caused by the larvae of Toxocara, is unspecified, and it seems factors such as the number of larvae can play a basic role for the emergence of alterations.

  11. Rat Liver Enzyme Release Depends on Blood Flow-Bearing Physical Forces Acting in Endothelium Glycocalyx rather than on Liver Damage

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    Julieta A. Díaz-Juárez

    2017-01-01

    Full Text Available We have found selective elevation of serum enzyme activities in rats subjected to partial hepatectomy (PH, apparently controlled by hemodynamic flow-bearing physical forces. Here, we assess the involvement of stretch-sensitive calcium channels and calcium mobilization in isolated livers, after chemical modifications of the endothelial glycocalyx and changing perfusion directionality. Inhibiting in vivo protein synthesis, we found that liver enzyme release is influenced by de novo synthesis of endothelial glycocalyx components, and released enzymes are confined into a liver “pool.” Moreover, liver enzyme release depended on extracellular calcium entry possibly mediated by stretch-sensitive calcium channels, and this endothelial-mediated mechanotransduction in liver enzyme release was also evidenced by modifying the glycocalyx carbohydrate components, directionality of perfusing flow rate, and the participation of nitric oxide (NO and malondialdehyde (MDA, leading to modifications in the intracellular distribution of these enzymes mainly as nuclear enrichment of “mitochondrial” enzymes. In conclusion, the flow-induced shear stress may provide fine-tuned control of released hepatic enzymes through mediation by the endothelium glycocalyx, which provides evidence of a biological role of the enzyme release rather to be merely a biomarker for evaluating hepatotoxicity and liver damage, actually positively influencing progression of liver regeneration in mammals.

  12. Failure of Chemotherapy in Hepatocellular Carcinoma Due to Impaired and Dysregulated Primary Liver Drug Metabolizing Enzymes and Drug Transport Proteins: What to Do?

    Science.gov (United States)

    Ul Islam, Salman; Ahmed, Muhammad Bilal; Shehzad, Adeeb; Ul-Islam, Mazhar; Lee, Young Sup

    2018-05-28

    Most of the drugs are metabolized in the liver by the action of drug metabolizing enzymes. In hepatocellular carcinoma (HCC), primary drug metabolizing enzymes are severely dysregulated, leading to failure of chemotherapy. Sorafenib is the only standard systemic drug available, but it still presents certain limitations, and much effort is required to understand who is responsive and who is refractory to the drug. Preventive and therapeutic approaches other than systemic chemotherapy include vaccination, chemoprevention, liver transplantation, surgical resection, and locoregional therapies. This review details the dysregulation of primary drug metabolizing enzymes and drug transport proteins of the liver in HCC and their influence on chemotherapeutic drugs. Furthermore, it emphasizes the adoption of safe alternative therapeutic strategies to chemotherapy. The future of HCC treatment should emphasize the understanding of resistance mechanisms and the finding of novel, safe, and efficacious therapeutic strategies, which will surely benefit patients affected by advanced HCC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Prevalence of abnormal plasma liver enzymes in older people with Type 2 diabetes.

    Science.gov (United States)

    Morling, J R; Strachan, M W J; Hayes, P C; Butcher, I; Frier, B M; Reynolds, R M; Price, J F

    2012-04-01

    To determine the prevalence and distribution of abnormal plasma liver enzymes in a representative sample of older adults with Type 2 diabetes. Plasma concentrations of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase were measured in a randomly selected, population-based cohort of 1066 men and women aged 60-75 years with Type 2 diabetes (the Edinburgh Type 2 Diabetes Study). Overall, 29.1% (95% CI 26.1-31.8) of patients had one or more plasma liver enzymes above the upper limit of the normal reference range. Only 10.1% of these patients had a prior history of liver disease and a further 12.4% reported alcohol intake above recommended limits. Alanine aminotransferase was the most commonly raised liver enzyme (23.1% of patients). The prevalence of abnormal liver enzymes was significantly higher in men (odds ratio 1.40, 95% CI 1.07-1.83), in the youngest 5-year age band (odds ratio 2.02, 95% CI 1.44-2.84), in patients with diabetes duration enzyme abnormality. The prevalence of elevated liver enzymes in people with Type 2 diabetes is high, with only modest variation between clinically defined patient groups. Further research is required to determine the prognostic value of raised, routinely measured liver enzymes to inform decisions on appropriate follow-up investigations. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

  14. Effects of dexamethasone on liver enzymes and some serum ...

    African Journals Online (AJOL)

    Concomitant usage of dexamethasone and other medications may alter electrolyte metabolism and increase the formation of potentially hepatotoxic reactive metabolites which can contribute to elevated liver enzymes. The role of dexamethasone in liver functions and electrolyte metabolism during pregnancy in Yankasa ...

  15. Changes in Liver Function Enzymes of HIV/AIDS Patients Treated ...

    African Journals Online (AJOL)

    user

    on liver enzyme markers (Aspartate aminotransferase, Alanine aminotransferase ... the diagnosis and advanced infection of the liver cells by HIV. ... recommended guideline for the treatment of HIV ... HIV-positive patients not on treatment and.

  16. Biochemical assessement of liver enzymes in immunocompromised ...

    African Journals Online (AJOL)

    Aim: This study aims at the estimation of serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), Aspartate aminotransferase (AST), and glutmyltransferase GGT (Liver enzymes) in Human immunodeficiency virus(HIV) and/or Acquired immune deficiency syndrome(AIDS) patients in parts of Edo State, Nigeria.

  17. A case of moderate liver enzyme elevation after acute acetaminophen overdose despite undetectable acetaminophen level and normal initial liver enzymes.

    Science.gov (United States)

    Bebarta, Vikhyat S; Shiner, Drew C; Varney, Shawn M

    2014-01-01

    Liver function test (LFT) increase is an early sign of acetaminophen (APAP) toxicity. Typically, when an acute overdose patient is evaluated and has an initial undetectable APAP level and normal liver enzymes, the patient is not treated with N-acetylcysteine, and liver enzymes are not expected to increase later. We report a case of moderate LFT increase despite normal LFTs and an undetectable APAP level after delayed presentation of an APAP ingestion. A 22-year-old male with no medical history ingested 15-25 hydrocodone/APAP tablets (5 mg/500 mg). His suicide note and his bunkmate corroborated the overdose time. He arrived at the emergency department 16 hours after ingestion. At that time, his APAP level was enzymes were normal [aspartate transaminase (AST) 31 U/L and alanine transaminase (ALT) 34 U/L]. Twenty-nine hours after ingestion, the psychiatry team obtained LFTs (AST 45, ALT 61). He had persistent nausea and diffuse abdominal pain. On repeat analysis, the APAP level at 36 hours was found to be <10 μg/mL, AST 150, and ALT 204. After 2 more days of increasing LFTs and persistent abdominal pain and nausea, the toxicology department was consulted, the patient was transferred to the medicine department, and intravenous N-acetylcysteine was started 66 hours after ingestion. He was treated for 16 hours and had a significant decline in LFTs and symptom resolution. His prothrombin time, bilirubin, lactate, creatinine, and mental status were normal throughout the admission. Other cases of LFT increase were excluded. Our case report illustrates that a moderate increase in liver transaminase may occur despite an initial undetectable APAP level and normal transaminases after a delayed presentation. In our case, no serious clinical effects were reported.

  18. Association of liver enzymes and computed tomography markers of liver steatosis with familial longevity.

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    Michiel Sala

    Full Text Available OBJECTIVE: Familial longevity is marked by enhanced peripheral but not hepatic insulin sensitivity. The liver has a critical role in the pathogenesis of hepatic insulin resistance. Therefore we hypothesized that the extent of liver steatosis would be similar between offspring of long-lived siblings and control subjects. To test our hypothesis, we investigated the extent of liver steatosis in non-diabetic offspring of long-lived siblings and age-matched controls by measuring liver enzymes in plasma and liver fat by computed tomography (CT. RESEARCH DESIGN AND METHODS: We measured nonfasting alanine transaminase (ALT, aspartate aminotransferase (AST, and Υ-glutamyl transferase (GGT in 1625 subjects (736 men, mean age 59.1 years from the Leiden Longevity Study, comprising offspring of long-lived siblings and partners thereof. In a random subgroup, fasting serum samples (n = 230 were evaluated and CT was performed (n = 268 for assessment of liver-spleen (L/S ratio and the prevalence of moderate-to-severe non-alcoholic fatty liver disease (NAFLD. Linear mixed model analysis was performed adjusting for age, gender, body mass index, smoking, use of alcohol and hepatotoxic medication, and correlation of sibling relationship. RESULTS: Offspring of long-lived siblings had higher nonfasting ALT levels as compared to control subjects (24.3 mmol/L versus 23.2 mmol/L, p = 0.03, while AST and GGT levels were similar between the two groups. All fasting liver enzyme levels were similar between the two groups. CT L/S ratio and prevalence of moderate-to-severe NAFLD was similar between groups (1.12 vs 1.14, p = 0.25 and 8% versus 8%, p = 0.91, respectively. CONCLUSIONS: Except for nonfasting levels of ALT, which were slightly higher in the offspring of long-lived siblings compared to controls, no differences were found between groups in the extent of liver steatosis, as assessed with liver biochemical tests and CT. Thus, our data indicate that the extent of liver

  19. Association of liver enzymes and computed tomography markers of liver steatosis with familial longevity.

    Science.gov (United States)

    Sala, Michiel; Kroft, Lucia J M; Röell, Boudewijn; van der Grond, Jeroen; Slagboom, P Eline; Mooijaart, Simon P; de Roos, Albert; van Heemst, Diana

    2014-01-01

    Familial longevity is marked by enhanced peripheral but not hepatic insulin sensitivity. The liver has a critical role in the pathogenesis of hepatic insulin resistance. Therefore we hypothesized that the extent of liver steatosis would be similar between offspring of long-lived siblings and control subjects. To test our hypothesis, we investigated the extent of liver steatosis in non-diabetic offspring of long-lived siblings and age-matched controls by measuring liver enzymes in plasma and liver fat by computed tomography (CT). We measured nonfasting alanine transaminase (ALT), aspartate aminotransferase (AST), and Υ-glutamyl transferase (GGT) in 1625 subjects (736 men, mean age 59.1 years) from the Leiden Longevity Study, comprising offspring of long-lived siblings and partners thereof. In a random subgroup, fasting serum samples (n = 230) were evaluated and CT was performed (n = 268) for assessment of liver-spleen (L/S) ratio and the prevalence of moderate-to-severe non-alcoholic fatty liver disease (NAFLD). Linear mixed model analysis was performed adjusting for age, gender, body mass index, smoking, use of alcohol and hepatotoxic medication, and correlation of sibling relationship. Offspring of long-lived siblings had higher nonfasting ALT levels as compared to control subjects (24.3 mmol/L versus 23.2 mmol/L, p = 0.03), while AST and GGT levels were similar between the two groups. All fasting liver enzyme levels were similar between the two groups. CT L/S ratio and prevalence of moderate-to-severe NAFLD was similar between groups (1.12 vs 1.14, p = 0.25 and 8% versus 8%, p = 0.91, respectively). Except for nonfasting levels of ALT, which were slightly higher in the offspring of long-lived siblings compared to controls, no differences were found between groups in the extent of liver steatosis, as assessed with liver biochemical tests and CT. Thus, our data indicate that the extent of liver steatosis is similar between offspring of long-lived siblings and

  20. CHANGES IN SERUM ENZYMES LEVELS ASSOCIATED WITH LIVER FUNCTIONS IN STRESSED MARWARI GOAT

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    Kataria N.

    2011-03-01

    Full Text Available Serum enzyme levels were determined in goats of Marwari breed belonging to farmers’ stock of arid tract of Rajasthan state, India. The animals were grouped into healthy and stressed comprising of gastrointestinal parasiticised, pneumonia affected, and drought affected. The serum enzymes determined were sorbitol dehydrogenase, malate dehydrogenase, glucose-6-phosphate dehydrogenase, glutamate dehydrogenase, ornithine carbamoyl transferase, gamma-glutamayl transferase, 5’nucleotidase, glucose-6-phosphatase, arginase, and aldolase. In stressed group the mean values of all the enzymes increased significantly (p≤0.05 as compared to respective healthy mean value. All the enzymes showed highest values in the gastrointestinal parasiticised animals and least values in the animals having pneumonia. In gastrointestinal parasiticised animals maximum change was observed in G-6-Pase activity and minimum change was observed in malate dehydrogenase mean value. It was concluded that Increased activity of all the serum enzymes was due to modulation of liver functions directly or indirectly.

  1. Mammalian folylpoly-γ-glutamate synthetase. 1. Purification and general properties of the hog liver enzyme

    International Nuclear Information System (INIS)

    Cichowicz, D.J.; Shane, B.

    1987-01-01

    Folylpolyglutamate synthetase was purified 30,000-150,000-fold from hog liver. Purification required the use of protease inhibitors, and the protein was purified to homogeneity in two forms. Both forms of the enzyme were monomers of M/sub r/ 62,000 and had similar specific activities. The specific activity of the homogeneous protein was over 2000-fold higher than reported for partially purified folylpolyglutamate synthetases from other mammalian sources. Enzyme activity was absolutely dependent on the presence of a reducing agent and a monovalent cation, of which K + was most effective. The purified enzyme catalyzed a MgATP-dependent addition of glutamate to tetrahydrofolate with the concomitant stoichiometric formation of MgADP and phosphate. Under conditions that resembled the expected substrate and enzyme concentrations in hog liver, tetrahydrofolate was metabolized to long glutamate chain length derivatives with the hexaglutamate, the major in vivo folate derivative, predominating. Enzyme activity was maximal at about pH 9.5. The high-pH optimum was primarily due to an increase in the K/sub m/ value for the L-glutamate substrate at lower pH values, and the reaction proceeded effectively at physiological pH provided high levels of glutamate were supplied

  2. Acute cadmium intoxication induces alpha-class glutathione S-transferase protein synthesis and enzyme activity in rat liver

    International Nuclear Information System (INIS)

    Casalino, Elisabetta; Sblano, Cesare; Calzaretti, Giovanna; Landriscina, Clemente

    2006-01-01

    Acute cadmium intoxication affects glutathione S-transferase (GST) in rat liver. It has been found that 24 h after i.p. cadmium administration to rats, at a dose of 2.5 mg CdCl 2 kg -1 body weight, the activity of this enzyme in liver cytosol increased by 40%. A less stimulatory effect persisted till 48 h and thereafter the enzyme activity normalized. Since, GST isoenzymes belong to different classes in mammalian tissues, we used quantitative immunoassays to verify which family of GST isoenzymes is influenced by this intoxication. Only alpha-class glutathione S-transferase (α-GST) proteins were detected in rat liver cytosol and their level increased by about 25%, 24 h after cadmium treatment. No pi-GST isoforms were found in liver cytosol from either normal or cadmium-treated rats. Co-administration of actinomycin D with cadmium normalized both the protein level and the activity of α-GST, suggesting that some effect occurs on enzyme transcription of these isoenzymes by this metal. On the other hand, it seems unlikely that the stimulatory effect is due to the high level of peroxides caused by lipid peroxidation, since Vitamin E administration strongly reduced the TBARS level, but did not cause any GST activity decrease

  3. Coffee bean extracts rich and poor in kahweol both give rise to elevation of liver enzymes in healthy volunteers

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    Schouten Evert G

    2004-07-01

    Full Text Available Abstract Background Coffee oil potently raises serum cholesterol levels in humans. The diterpenes cafestol and kahweol are responsible for this elevation. Coffee oil also causes elevation of liver enzyme levels in serum. It has been suggested that cafestol is mainly responsible for the effect on serum cholesterol levels and that kahweol is mainly responsible for the effect on liver enzyme levels. The objective of this study was to investigate whether coffee oil that only contains a minute amount of kahweol indeed does not cause elevation of liver enzyme levels. Methods The response of serum alanine aminotransferase (ALAT and aspartate aminotransferase (ASAT to Robusta coffee oil (62 mg/day cafestol, 1.6 mg/day kahweol was measured in 18 healthy volunteers. Results After nine days one subject was taken off Robusta oil treatment due to an ALAT level of 3.6 times the upper limit of normal (ULN. Another two subjects stopped treatment due to other reasons. After 16 days another two subjects were taken off Robusta oil treatment. One of those subjects had levels of 5.8 ULN for ALAT and 2.0 ULN for ASAT; the other subject had an ALAT level of 12.4 ULN and an ASAT level of 4.7 ULN. It was then decided to terminate the study. The median response of subjects to Robusta oil after 16 days was 0.27 ULN (n = 15, 25th,75th percentile: 0.09;0.53 for ALAT and 0.06 ULN (25th,75th percentile -0.06;0.22 for ASAT. Conclusions We conclude that the effect on liver enzyme levels of coffee oil containing hardly any kahweol is similar to that of coffee oil containing high amounts of kahweol. Therefore it is unlikely that kahweol is the component of coffee oil that is responsible for the effect. Furthermore, we conclude that otherwise unexplained elevation of liver enzyme levels observed in patients might be caused by a switch from consumption of filtered coffee to unfiltered coffee.

  4. MATERNAL HEMOLYSIS, ELEVATED LIVER-ENZYMES AND LOW PLATELETS SYNDROME - SPECIFIC PROBLEMS IN THE NEWBORN

    NARCIS (Netherlands)

    EELTINK, CM; VANLINGEN, RA; AARNOUDSE, JG; DERKS, JB; OKKEN, A

    To evaluate the effects of maternal haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome on the fetus and neonate we retrospectively investigated the outcome of 87 pregnancies. All women showed thrombocytopenia, elevated liver enzymes and haemolysis. None of them died. Nine infants

  5. Reactivation in vitro of zinc-requiring apo-enzymes by rat liver zinc-thionein

    OpenAIRE

    Udom, Albert O.; Brady, Frank O.

    1980-01-01

    The ability of rat liver zinc-thionein to donate its metal to the apo-enzymes of the zinc enzymes horse liver alcohol dehydrogenase, yeast aldolase, thermolysin, Escherichia coli alkaline phosphatase and bovine erythrocyte carbonic anhydrase was investigated. Zinc-thionein was as good as, or better than, ZnSO4, Zn(CH3CO2)2 or Zn(NO3)2 in donating its zinc to these apo-enzymes. Apo-(alcohol dehydrogenase) could not be reactivated by zinc salts or by zinc-thionein. Incubation of the other apo-e...

  6. The effects of gender, age, ethnicity, and liver cirrhosis on cytochrome P450 enzyme activity in human liver microsomes and inducibility in cultured human hepatocytes

    International Nuclear Information System (INIS)

    Parkinson, Andrew; Mudra, Daniel R.; Johnson, Cory; Dwyer, Anne; Carroll, Kathleen M.

    2004-01-01

    We have measured cytochrome P450 (CYP) activity in nearly 150 samples of human liver microsomes and 64 samples of cryopreserved human hepatocytes, and we have performed induction studies in over 90 preparations of cultured human hepatocytes. We have analyzed these data to examine whether the expression of CYP enzyme activity in liver microsomes and isolated hepatocytes or the inducibility of CYP enzymes in cultured hepatocytes is influenced by the gender, age, or ethnicity of the donor (the latter being limited to Caucasians, African Americans, and Hispanics due to a paucity of livers from Asian donors). In human liver microsomes, there were no statistically significant differences (P > 0.05) in CYP activity as a function of age, gender, or ethnicity with one exception. 7-Ethoxyresorufin O-dealkylase (CYP1A2) activity was greater in males than females, which is consistent with clinical observation. Liver microsomal testosterone 6β-hydroxylase (CYP3A4) activity was slightly greater in females than males, but the difference was not significant. However, in cryopreserved human hepatocytes, the gender difference in CYP3A4 activity (females = twice males) did reach statistical significance, which supports the clinical observation that females metabolize certain CYP3A4 substrates faster than do males. Compared with those from Caucasians and African Americans, liver microsomes from Hispanics had about twice the average activity of CYP2A6, CYP2B6, and CYP2C8 and half the activity of CYP1A2, although this apparent ethnic difference may be a consequence of the relatively low number of Hispanic donors. Primary cultures of hepatocytes were treated with β-naphthoflavone, an inducer of CYP1A2, phenobarbital or rifampin, both of which induce CYP2B6, CYP2C9, CYP2C19, and CYP3A4, albeit it to different extents. Induction of these CYP enzymes in freshly cultured hepatocytes did not appear to be influenced by the gender or age of the donor. Furthermore, CYP3A4 induction in

  7. Role of Liver Function Enzymes in Diagnosis of Choledocholithiasis in Biliary Colic Patients

    Directory of Open Access Journals (Sweden)

    Mohammad Hussein Mirshamsi

    2011-10-01

    Full Text Available Liver functional tests due to inflammatory process which induced by cholecystitis might changed and some clinicians suggested that these changes might help us to stone prediction in common bile ducts and decrease hazards of performing ERCP and other invasive procedures. Present study was performed for assessment of role of liver functional test in diagnosis of common bile duct stone in patients with cholecystitis and help in their management. Present prospective study was performed between April 2010 and March 2011 on 350 patients who come to our hospital with cholecystitis or biliary colic diagnosis. Patients with cholesistitis diagnosis were underwent operation for removing gall bladder stone and retrograde cholangiopancreatography (ERCP was performed for patients with suspicious to biliary colic and common bile duct (CBD stones. Ultrasonography, Aspartate Aminotransferases (AST, Alanine Aminotransferases (ALT, Alkaline Phosphatase (ALP and direct and total serum bilirubin were measured for all of participated patients. Mean of AST. ALT, ALP and total and direct bilirubin were had no significant differences between two study groups. In logistic regression analysis, after entering into the model only CBD diameter (OR: 20; P=0.00 and elevated serum level of ALT (OR: 2; P=0.04 were remained into the model and were known as independent predictor of cholelithiasis. Elevated level of liver enzymes had not main role in CBD diagnosis and ERCP had no to perform for suspicious CBD stone only with elevated liver enzyme and even with normal ultrasonography findings. Endosonography as non invasive procedure recommend for patients before ERCP.

  8. Subcellular distribution of histone-degrading enzyme activities from rat liver

    International Nuclear Information System (INIS)

    Heinrich, P.C.; Raydt, G.; Puschendorf, B.; Jusic, M.

    1976-01-01

    Chromatin prepared from liver tissue contains a histone-degrading enzyme activity with a pH optimum of 7.5-8.0, whereas chromatin isolated from purified nuclei is devoid of it. The histone-degrading enzyme activity was assayed with radioactively labelled total histones from Ehrlich ascites tumor cells. Among the different subcellular fractions assayed, only lysosomes and mitochondria exhibited histone-degrading enzymes. A pH optimum around 4.0-5.0 was found for the lysosomal fraction, whereas 7.5-8.0 has been found for mitochondria. Binding studies of frozen and thawed lysosomes or mitochondria to proteinase-free chromatin demonstrate that the proteinase associated with chromatin isolated from frozen tissue originates from damaged mitochondria. The protein degradation patterns obtained after acrylamide gel electrophoresis are similar for the chromatin-associated and the mitochondrial proteinase and different from that obtained after incubation with lysosomes. The chromatin-associated proteinase as well as the mitochondrial proteinase are strongly inhibited by 1.0 mM phenylmethanesulfonyl fluoride. Weak inhibition is found for lysosomal proteinases at pH 5. Kallikrein-trypsin inhibitor, however, inhibits lysosomal proteinase activity and has no effect on either chromatin-associated or mitochondrial proteinases. The higher template activity of chromatin isolated from a total homogenate compared to chromatin prepared from nuclei may be due to the presence of this histone-degrading enzyme activity. (orig.) [de

  9. Short-term calorie restriction feminizes the mRNA profiles of drug metabolizing enzymes and transporters in livers of mice

    International Nuclear Information System (INIS)

    Fu, Zidong Donna; Klaassen, Curtis D.

    2014-01-01

    Calorie restriction (CR) is one of the most effective anti-aging interventions in mammals. A modern theory suggests that aging results from a decline in detoxification capabilities and thus accumulation of damaged macromolecules. The present study aimed to determine how short-term CR alters mRNA profiles of genes that encode metabolism and detoxification machinery in the liver. Male C57BL/6 mice were fed CR (0, 15, 30, or 40%) diets for one month, followed by mRNA quantification of 98 xenobiotic processing genes (XPGs) in the liver, including 7 uptake transporters, 39 phase-I enzymes, 37 phase-II enzymes, 10 efflux transporters, and 5 transcription factors. In general, 15% CR did not alter mRNAs of most XPGs, whereas 30 and 40% CR altered over half of the XPGs (32 increased and 29 decreased). CR up-regulated some phase-I enzymes (fold increase), such as Cyp4a14 (12), Por (2.3), Nqo1 (1.4), Fmo2 (5.4), and Fmo3 (346), and numerous number of phase-II enzymes, such as Sult1a1 (1.2), Sult1d1 (2.0), Sult1e1 (33), Sult3a1 (2.2), Gsta4 (1.3), Gstm2 (1.3), Gstm3 (1.7), and Mgst3 (2.2). CR feminized the mRNA profiles of 32 XPGs in livers of male mice. For instance, CR decreased the male-predominantly expressed Oatp1a1 (97%) and increased the female-predominantly expressed Oatp1a4 (11). In conclusion, short-term CR alters the mRNA levels of over half of the 98 XPGs quantified in livers of male mice, and over half of these alterations appear to be due to feminization of the liver. - Highlights: • Utilized a graded CR model in male mice • The mRNA profiles of xenobiotic processing genes (XPGs) in liver were investigated. • CR up-regulates many phase-II enzymes. • CR tends to feminize the mRNA profiles of XPGs

  10. Short-term calorie restriction feminizes the mRNA profiles of drug metabolizing enzymes and transporters in livers of mice

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Zidong Donna [Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160 (United States); Klaassen, Curtis D., E-mail: cklaasse@kumc.edu [Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66160 (United States)

    2014-01-01

    Calorie restriction (CR) is one of the most effective anti-aging interventions in mammals. A modern theory suggests that aging results from a decline in detoxification capabilities and thus accumulation of damaged macromolecules. The present study aimed to determine how short-term CR alters mRNA profiles of genes that encode metabolism and detoxification machinery in the liver. Male C57BL/6 mice were fed CR (0, 15, 30, or 40%) diets for one month, followed by mRNA quantification of 98 xenobiotic processing genes (XPGs) in the liver, including 7 uptake transporters, 39 phase-I enzymes, 37 phase-II enzymes, 10 efflux transporters, and 5 transcription factors. In general, 15% CR did not alter mRNAs of most XPGs, whereas 30 and 40% CR altered over half of the XPGs (32 increased and 29 decreased). CR up-regulated some phase-I enzymes (fold increase), such as Cyp4a14 (12), Por (2.3), Nqo1 (1.4), Fmo2 (5.4), and Fmo3 (346), and numerous number of phase-II enzymes, such as Sult1a1 (1.2), Sult1d1 (2.0), Sult1e1 (33), Sult3a1 (2.2), Gsta4 (1.3), Gstm2 (1.3), Gstm3 (1.7), and Mgst3 (2.2). CR feminized the mRNA profiles of 32 XPGs in livers of male mice. For instance, CR decreased the male-predominantly expressed Oatp1a1 (97%) and increased the female-predominantly expressed Oatp1a4 (11). In conclusion, short-term CR alters the mRNA levels of over half of the 98 XPGs quantified in livers of male mice, and over half of these alterations appear to be due to feminization of the liver. - Highlights: • Utilized a graded CR model in male mice • The mRNA profiles of xenobiotic processing genes (XPGs) in liver were investigated. • CR up-regulates many phase-II enzymes. • CR tends to feminize the mRNA profiles of XPGs.

  11. Increased serum levels of hyaluronic acid in pregnancies complicated by preeclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome.

    Science.gov (United States)

    Osmers, R G; Schütz, E; Diedrich, F; Wehry, B; Krauss, T; Oellerich, M; Kuhn, W

    1998-02-01

    Fifteen percent of patients who later have hemolysis, elevated liver enzymes, and low platelets syndrome develop initially have nonspecific symptoms. Early diagnosis could ensure adequate obstetric management; however, prognostic biochemical tests are lacking. We hypothesized that elevated hyaluronic acid serum levels might be an early indicator of hemolysis, elevated liver enzymes, and low platelets syndrome because it is known to be a sensitive marker of liver cell function. Hyaluronic acid in serum was measured in patients with normal pregnancies (n = 109) and in those patients with pregnancies complicated by preeclampsia (n = 14) or hemolysis, elevated liver enzymes, and low platelets syndrome (n = 11). A significant increase in hyaluronic acid serum concentrations was observed in patients with hemolysis, elevated liver enzymes, and low platelets syndrome or with preeclampsia (p hyaluronic acid serum levels in hemolysis, elevated liver enzymes, and low platelets syndrome correlated with the clinical severity of the individual course of disease as measured by intensive care unit time (r = 0.72; p hyaluronic acid in preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome are significantly elevated and might play an important diagnostic and prognostic role in patients with hemolysis, elevated liver enzymes, and low platelets syndrome.

  12. Liver enzymes and markers of inflammation in Nigerian adults with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Udenze Ifeoma Christiana

    2015-01-01

    Full Text Available Aims and objectives: The aim of this study is to determine the plasma levels of the liver enzymes alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT, and lactate dehydrogenase (LDH in people with metabolic syndrome and to determine the association between the liver enzymes and obesity, insulin resistance, interleukin 6 (IL-6, and C-reactive protein (CRP in adult Nigerians with metabolic syndrome. Materials and Methods: This was a case control study of 50 adult men and women with metabolic syndrome, and 50 age- and sex-matched males and females without metabolic syndrome. Metabolic syndrome was defined based on the National Cholesterol Education Program (NCEP-Adult Treatment Panel III (ATPIII criteria. Written informed consent was obtained from the participants. Sociodemographic and clinical data were collected using a structured questionnaire. Venous blood was collected after an overnight fast. The ethics committee of the Lagos University Teaching Hospital in Lagos, Nigeria, approved the study protocol. Comparison of continuous variables was done using the student′s t-test. Regression and correlation analysis were used to determine the associations between variables. Statistical significance was set at P < 0.05. Results: There was a statistically significant increase in the liver enzymes ALP (P = 0.031, ALT (P = 0.019, and GGT (P = 0.037, as well as in the inflammatory markers CRP (P = 0.019 and the cytokine IL-6 (P = 0.040 between the two study groups. ALP and ALT showed significant correlation with waist circumference, BMI, fasting insulin, and waist/hip ratio (P < 0.05. Multivariate regression also identified ALT, AST, and ALP to be associated with IL-6 and CRP (P < 0.05. Conclusion: Liver enzyme levels were increased in metabolic syndrome and associated with obesity, fasting insulin, and CRP. Elevated liver enzymes may indicate dysmetabolism and increased

  13. Superoxide Dismutase (SOD Enzyme Activity Assay in Fasciola spp. Para-sites and Liver Tissue Extract

    Directory of Open Access Journals (Sweden)

    M Assady

    2011-09-01

    Full Text Available Background: The purpose of this comparative study was to detect superoxide dismutase (SOD activities in Fasciola hepatica, F. gigantica parasites, infected and healthy liver tissues in order to determine of species effects and liver infection on SODs activity level.Methods: Fasciola spp. parasites and sheep liver tissues (healthy and infected liver tissues, 10 samples for each, were collected, homogenized and investigated for protein measurement, protein detection and SOD enzyme activity assay. Protein concentration was measured by Bradford method and SODs band protein was detected on SDS-PAGE. SODs activity was determined by iodonitrotetrazolium chloride, INT, and xanthine substrates. Independent samples t-test was conducted for analysis of SODs activities difference.Results: Protein concentration means were detected for F. hepatica 1.3 mg/ ml, F. gigantica 2.9 mg/ml, healthy liver tissue 5.5 mg/ml and infected liver tissue 1.6 mg/ml (with similar weight sample mass. Specific enzyme activities in the samples were obtained 0.58, 0.57, 0.51, 1.43 U/mg for F. hepatica, F. gigantica, healthy liver and infected liver respectively. Gel electrophoresis of Fasciola spp. and sheep liver tissue extracts revealed a band protein with MW of 60 kDa. The statistical analysis revealed significant difference between SOD activities of Fasciola species and also between SOD activity of liver tissues (P<.05.Conclusion: Fasciola species and liver infection are effective causes on SOD enzyme activity level.

  14. Angiotensin converting enzyme (ACE) gene expression in experimentally induced liver cirrhosis in rats.

    Science.gov (United States)

    Shahid, Syed Muhammad; Fatima, Syeda Nuzhat; Mahboob, Tabassum

    2013-09-01

    Angiotensin converting enzyme (ACE) is a key player of Renin Angiotensin System (RAS), involved in conversion of active product, angiotensin-II. Alterations in RAS have been implicated in the pathophysiology of various diseases involving heart, kidney, lung and liver. This study is designed to investigate the association of ACE gene expression in induction of liver cirrhosis in rats. Total 12 male albino Wistar rats were selected and divided in two groups. Control group received 0.9% NaCl, where as Test group received thioacidamide (TAA), dissolved in 0.9%NaCl, injected intraperitoneally at a dosage of 200mg/Kg of body weight, twice a week for 12 weeks. The rats were decapitated and blood sample was collected at the end of experimental period and used for liver functions, enzyme activity, antioxidant enzymes and lipid peroxidation estimations. Genomic DNA was isolated from excised tissue determine the ACE genotypes using specific primers. The ACE gene expression in liver tissue was assessed using the quantitative RT-PCR method. The activity of ALT, total and direct bilirubin, SOD and CAT levels were significantly high (pACE gene expression after 12 weeks TAA treatment in cirrhotic rats was significantly increased (pACE gene expression. The finding of major up-regulation of ACE in the experimental rat liver provides further insight into the complexities of the RAS and its regulation in liver injury. The development of specific modulators of ACE activity and function, in future, will help determine the role of ACE and its genetic variants in the pathophysiology of liver disease.

  15. The effect of aqueous extract of Avicennia marina (Forsk. Vierh. leaves on liver enzymes' activity, oxidative stress parameters and liver histopathology in male diabetic rats

    Directory of Open Access Journals (Sweden)

    Akram Hamzevi

    2017-12-01

    Full Text Available Background: Avicennia marina has antioxidant and anti-diabetic properties. This study was conducted to examine the effect of aqueous extract of A. marina on liver enzymes' activity, oxidative stress parameters and liver histopathology in diabetic rats. Materials and Methods: In this experimental study, 28 male rats were allocated into the equal groups of control, diabetic control and experimental diabetic 1 and 2. The diabetes in diabetic control and experimental diabetic groups was induced using an intraperitoneal injection of 120 mg/kg alloxan. The experimental diabetic groups received the aqueous extract of A. marina (100 and 200 mg/kg, i.p. in alternate days for one month. Sterile distilled water was injected to the animals of control and diabetic control groups. At the end of the treatment period, serum levels of ALT, AST, GGT and ALP were measured. Then, levels of SOD, GST, CAT and MDA were measured in the liver tissue. The liver sections were prepared and examined by an optical microscope. Results: Results showed that administration of the A. marina extract (100 and 300 mg/kg, ip to the diabetic rats significantly decreased the serum levels of liver enzymes and tissue level of MDA. Also, the activity of the liver tissue's antioxidant enzymes was increased (P<0.05. The A. marina extract dose-dependently decreased liver damages in diabetic rats. Conclusion: Administration of the A. marina extract improves liver tissue oxidative stress indices and decreases the serum level of liver enzymes. Also, A. marina extract improves liver tissue injuries induced by diabetes.

  16. Associated liver enzymes with hyperlipidemic profile in type 2 diabetes patients.

    Science.gov (United States)

    Al-Jameil, Noura; Khan, Farah A; Arjumand, Sadia; Khan, Mohammad F; Tabassum, Hajera

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and is associated with dyslipidemia and disturbed liver function. Aim of the present work is to assess the liver enzymes and to find its association with hyperlipidemic profile in T2DM. Total of 157 subjects were studied and divided into two groups; diabetes (n=81) and non-diabetes (n=76). Various biochemical parameters like fasting glucose, post prandial glucose, HbA1c, total cholesterol (TC), triglycerides (Tg), high density lipoprotein cholesterol (HDL-C), alanine amino transferase (ALT), aspartate amino transferase (AST) and gamma-glutamyl transferase (GGT) were analyzed by ROCHE module Cobas 6000 (C501 & C601) analyzer, kits were procured by ROCHE diagnostics. Low density lipoprotein cholesterol (LDL-C) was estimated by Freidwald's formula. Statistical analysis was performed by applying student t test and Pearson's correlation coefficient, at 0.0001 and 0.05 level of significance, respectively. All the glycemic control parameters, lipid profile parameters except HDL-C and liver enzymes were found increased in diabetes group and significantly differ from non-diabetes group (p>0.0001). ALT showed significant positive correlation with fasting glucose, post prandial glucose, HbA1c, TC, Tg, LDL-C and GGT at p>0.05. AST showed very weak relation with all parameters while GGT was positively associated with fasting glucose, post prandial glucose, HbA1c, TC, Tg, LDL-C and ALT at p>0.05. In conclusion, T2DM incline to elevate liver enzymes, especially ALT and GGT were of significance. Routine screening of ALT and GGT in T2DM patients may assists early detection of liver abnormalities and to arrest the progress of disease.

  17. Health behavior associated with liver enzymes among obese Korean adolescents, 2009-2014.

    Science.gov (United States)

    Lee, Eun-Young; Choi, Hwa Young; Cho, Hyunsoon; Kim, Bo Hyun; Ki, Moran

    2018-01-01

    Obesity is major risk factor for liver health. This study aimed to clarify whether specific health behaviors were associated with liver function in obese adolescents in Korea. Based on national school health examination data from 2009 to 2014, 25,142 obese or overweight students were examined for aspartate transaminase and alanine transaminase levels, and health behaviors. Multiple logistic regression was used to calculate the odds ratio for liver enzyme elevation. Subjects who thought of themselves as "very fat" had a 1.6 times higher odds ratio for liver enzyme elevations than those who thought of themselves as "normal." Those who consumed fast food 3 to 5 times weekly had 1.3 times higher odds ratio (OR = 1.27, 95% confidence interval = 1.05-1.54) for the elevation of ALT than those who did not consume fast food. Those who took sugar-sweetened beverage 3 to 5 times weekly had 1.2 times higher odds ratio (OR = 1.24, 95% confidence interval = 1.07-1.42) for the elevation of ALT than those who did not take it. Those who played computer game more than 2 hours a day showed 1.1 times higher odds ratio (OR = 1.10, 95% confidence interval = 1.01-1.21) for the elevation of ALT than those who did not. Specific food item and its frequency of consumption were identified for the positive and negative association with the elevation of liver enzymes. Self-image of body shape, sleeping time and need of help for alcohol or smoking problems also showed substantial association with the elevation.

  18. Short-term calorie restriction feminizes the mRNA profiles of drug metabolizing enzymes and transporters in livers of mice.

    Science.gov (United States)

    Fu, Zidong Donna; Klaassen, Curtis D

    2014-01-01

    Calorie restriction (CR) is one of the most effective anti-aging interventions in mammals. A modern theory suggests that aging results from a decline in detoxification capabilities and thus accumulation of damaged macromolecules. The present study aimed to determine how short-term CR alters mRNA profiles of genes that encode metabolism and detoxification machinery in the liver. Male C57BL/6 mice were fed CR (0, 15, 30, or 40%) diets for one month, followed by mRNA quantification of 98 xenobiotic processing genes (XPGs) in the liver, including 7 uptake transporters, 39 phase-I enzymes, 37 phase-II enzymes, 10 efflux transporters, and 5 transcription factors. In general, 15% CR did not alter mRNAs of most XPGs, whereas 30 and 40% CR altered over half of the XPGs (32 increased and 29 decreased). CR up-regulated some phase-I enzymes (fold increase), such as Cyp4a14 (12), Por (2.3), Nqo1 (1.4), Fmo2 (5.4), and Fmo3 (346), and numerous number of phase-II enzymes, such as Sult1a1 (1.2), Sult1d1 (2.0), Sult1e1 (33), Sult3a1 (2.2), Gsta4 (1.3), Gstm2 (1.3), Gstm3 (1.7), and Mgst3 (2.2). CR feminized the mRNA profiles of 32 XPGs in livers of male mice. For instance, CR decreased the male-predominantly expressed Oatp1a1 (97%) and increased the female-predominantly expressed Oatp1a4 (11). In conclusion, short-term CR alters the mRNA levels of over half of the 98 XPGs quantified in livers of male mice, and over half of these alterations appear to be due to feminization of the liver. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Comparing Effects of Medication Therapy and Exercise Training with Diet on Liver enzyme Levels and Liver Sonography in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD

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    Azadeh Nabizadeh Haghighi

    2016-03-01

    Full Text Available Background & Objectives: Non-alcoholic fatty liver disease, characterized by the deposition of fat in liver cells, can cause fibrosis, cirrhosis, and liver cell damage if not controlled. The aim of this study is to compare the effects of medication therapy and exercise training with diet on liver enzyme levels and liver sonography in patients with non-alcoholic fatty liver disease (NAFLD. Materials & Methods :In this quasi-experimental study, female patients with non-alcoholic fatty liver were randomly divided into two groups: medication therapy (n = 10 and exercise therapy (n = 10 for 8 weeks. During this period, the exercise group performed exercise training three days a week for 90 minutes per session. The drug was given to the medication group. In both groups, the diet was 500 calories less than their daily energy. Before and after intervention, blood tests and liver sonography were executed. All statistical analyses were done using SPSS for Windows version 20. Comparisons between and within groups were performed by Student's t-test and Wilcoxon test on paired and unpaired data. P < 0.05 was considered statistically significant. Results :In both groups, liver enzyme levels and disease severity in sonography reduced significantly (p<0.05. Conclusion: The findings of the present research showed that both methods of therapy have the same effect on reducing the severity of NAFLD.

  20. Liver enzymes and psychological well-being response to aerobic ...

    African Journals Online (AJOL)

    2014-06-02

    Jun 2, 2014 ... Background: Chronic hepatitis C (CHC) is a medical condition that has broad implications for a person's physical and ... Objective: The aim of this study was to detect changes in liver enzymes and psychological well-being in response to aerobic .... of mood that can be used to calculate a Total Mood.

  1. Correlation of secretory phospholipase-A2 activity and fatty acids in cerebrospinal fluid with liver enzymes tests

    Directory of Open Access Journals (Sweden)

    Sepideh Ghodoosifar

    2016-02-01

    Full Text Available Introduction: The aim was to determine whether secretory phospholipase-A2 (sPLA2 activity and fatty acids in cerebrospinal fluid (CSF are correlated with liver enzymes tests. Methods: CSF and serum samples were collected from 49 patients (age 18-65 as part of routine diagnostic testing. Along with serum liver enzymes aspartate aminotransferase (AST, alanine aminotransferase (ALT and alkaline phosphatase (ALP, the fatty acid composition of CSF was measured by gas liquid chromatography. CSF enzyme activities of sPLA2 were measured using the standard assay with diheptanoyl thio-phosphatidylcholin as substrate. Results: The saturated fatty acids (SFAs including palmitic acid and stearic acid were positively, and the unsaturated fatty acids including oleic acid and linoleic acid were negatively correlated with liver enzymes tests. In regression analysis with adjustment for body mass index (BMI, the elevated liver enzymes tests were positively associated with activity of sPLA2 (β > 0.31, P 0.38, P < 0.010 and negatively with total monounsaturated fatty acids (MUFAs (β < -0.40, P < 0.001 contents of CSF. Conclusion: CSF activity of sPLA2 and fatty acids may be linked to peripheral markers of liver function, suggesting an indirect impact of central fatty acids on hepatocytes function and metabolism.

  2. Health behavior associated with liver enzymes among obese Korean adolescents, 2009-2014.

    Directory of Open Access Journals (Sweden)

    Eun-Young Lee

    Full Text Available Obesity is major risk factor for liver health. This study aimed to clarify whether specific health behaviors were associated with liver function in obese adolescents in Korea.Based on national school health examination data from 2009 to 2014, 25,142 obese or overweight students were examined for aspartate transaminase and alanine transaminase levels, and health behaviors. Multiple logistic regression was used to calculate the odds ratio for liver enzyme elevation.Subjects who thought of themselves as "very fat" had a 1.6 times higher odds ratio for liver enzyme elevations than those who thought of themselves as "normal." Those who consumed fast food 3 to 5 times weekly had 1.3 times higher odds ratio (OR = 1.27, 95% confidence interval = 1.05-1.54 for the elevation of ALT than those who did not consume fast food. Those who took sugar-sweetened beverage 3 to 5 times weekly had 1.2 times higher odds ratio (OR = 1.24, 95% confidence interval = 1.07-1.42 for the elevation of ALT than those who did not take it. Those who played computer game more than 2 hours a day showed 1.1 times higher odds ratio (OR = 1.10, 95% confidence interval = 1.01-1.21 for the elevation of ALT than those who did not.Specific food item and its frequency of consumption were identified for the positive and negative association with the elevation of liver enzymes. Self-image of body shape, sleeping time and need of help for alcohol or smoking problems also showed substantial association with the elevation.

  3. Quantification of the glycogen cascade system: the ultrasensitive responses of liver glycogen synthase and muscle phosphorylase are due to distinctive regulatory designs

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    Venkatesh KV

    2005-05-01

    Full Text Available Abstract Background Signaling pathways include intricate networks of reversible covalent modification cycles. Such multicyclic enzyme cascades amplify the input stimulus, cause integration of multiple signals and exhibit sensitive output responses. Regulation of glycogen synthase and phosphorylase by reversible covalent modification cycles exemplifies signal transduction by enzyme cascades. Although this system for regulating glycogen synthesis and breakdown appears similar in all tissues, subtle differences have been identified. For example, phosphatase-1, a dephosphorylating enzyme of the system, is regulated quite differently in muscle and liver. Do these small differences in regulatory architecture affect the overall performance of the glycogen cascade in a specific tissue? We address this question by analyzing the regulatory structure of the glycogen cascade system in liver and muscle cells at steady state. Results The glycogen cascade system in liver and muscle cells was analyzed at steady state and the results were compared with literature data. We found that the cascade system exhibits highly sensitive switch-like responses to changes in cyclic AMP concentration and the outputs are surprisingly different in the two tissues. In muscle, glycogen phosphorylase is more sensitive than glycogen synthase to cyclic AMP, while the opposite is observed in liver. Furthermore, when the liver undergoes a transition from starved to fed-state, the futile cycle of simultaneous glycogen synthesis and degradation switches to reciprocal regulation. Under such a transition, different proportions of active glycogen synthase and phosphorylase can coexist due to the varying inhibition of glycogen-synthase phosphatase by active phosphorylase. Conclusion The highly sensitive responses of glycogen synthase in liver and phosphorylase in muscle to primary stimuli can be attributed to distinctive regulatory designs in the glycogen cascade system. The different

  4. Persistently and asymptomatic raised liver enzymes as a form of presentation of Wilson's disease at pediatric age

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    Catarina Matos

    2015-06-01

    Full Text Available Background: Wilson`s disease is a rare autosomal recessive disorder characterized by a change in the transport of copper in the liver, with progressive accumulation in this and other organs such as brain, kidney and cornea. Phenotypic expression of the disease varies widely and can range from elevated liver enzymes, fatty liver or gallstones in asymptomatic patients, to cirrhosis and fulminant hepatic failure, or disabling neuropsychiatric disease. Aim: To characterize a sample of patients with Wilson´s disease. Patients and Methods: Retrospective survey including children diagnosed with Wilson´s disease between 2002 and 2011 according to the criteria of the European Association for the Study of the Liver (2012. We analyzed family history; age, clinical data, imaging and histology at the time of diagnosis; genetic analysis; treatment and side effects; follow-up and current status. Results: We identified five patients. Three had a family history of disease. All were asymptomatic and had maintained raised liver enzymes. No patient had clinical stigmata of chronic liver disease. One female patient had overweight. All were treated with D-penicillamine, withdrawn in two patients because of side effects. Currently all patients remain asymptomatic, without evidence of progression of liver disease, with a median follow-up of 5 years and 3 months. Discussion: Our series show that Wilson´s disease may be present with raised liver enzymes in asymptomatic children. The overweight patient alerts us to screen the disease in overweight/obese patients with raised liver enzymes and/or steatosis persisting for more than six months after weight loss.

  5. Decrease in Activities of Selected Rat Liver Enzymes following ...

    African Journals Online (AJOL)

    The effects of the chemical effluent from Soap and Detergent Industry on some rat liver enzymes were investigated. Chemical analyses of both the effluent and tap water which served as the control were carried out before various concentrations of the effluent (5%v/v, 25%v/v, 50%v/v and 100%v/v) were made. The effluent ...

  6. Modulation of liver enzymes by an Iranian preparation of Echinacea purpurea

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    A. Manayi

    2015-10-01

    Full Text Available Hepatitis B, a common infectious disease of liver, is transmitted by blood and body fluids like semen and vaginal fluid that carry hepatitis B virus (HBV.  In chronic infection, medical care is required to decrease possibility of cirrhosis and liver cancer. In the present report, the hepatoprotective effect of an Echinacea purpurea preparation (Echiherb® has been described in a patient who suffered from HBV infection. The levels of both enzymes of aspartate aminotransferase (AST and alanine aminotransferase (ALT decreased to their normal level after 6 weeks of treatment. Therefore, this report may provide a new perspective for protection of liver in patients with HBV infection along with other diseases which damage liver cells using E. purpurea preparations.

  7. Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats

    Science.gov (United States)

    Kanter, Mehmet; Coskun, Omer; Budancamanak, Mustafa

    2005-01-01

    AIM: To investigate the effects of Nigella sativa L (NS) and Urtica dioica L (UD) on lipid peroxidation, antioxidant enzyme systems and liver enzymes in CCl4-treated rats. METHODS: Fifty-six healthy male Wistar albino rats were used in this study. The rats were randomly allotted into one of the four experimental groups: A (CCl4-only treated), B (CCl4+UD treated), C (CCl4+NS treated) and D (CCl4+UD+NS treated), each containing 14 animals. All groups received CCl4 (0.8 mL/kg of body weight, sc, twice a week for 60 d). In addition, B, C and D groups also received daily i.p. injections of 0.2 mL/kg NS or/and 2 mL/kg UD oils for 60 d. Group A, on the other hand, received only 2 mL/kg normal saline solution for 60 d. Blood samples for the biochemical analysis were taken by cardiac puncture from randomly chosen-seven rats in each treatment group at beginning and on the 60th d of the experiment. RESULTS: The CCl4 treatment for 60 d increased the lipid peroxidation and liver enzymes, and also decreased the antioxidant enzyme levels. NS or UD treatment (alone or combination) for 60 d decreased the elevated lipid peroxidation and liver enzyme levels and also increased the reduced antioxidant enzyme levels. The weight of rats decreased in group A, and increased in groups B, C and D. CONCLUSION: NS and UD decrease the lipid per-oxidation and liver enzymes, and increase the anti-oxidant defense system activity in the CCl4-treated rats. PMID:16425366

  8. Defining the optimal cut-off values for liver enzymes in diagnosing blunt liver injury.

    Science.gov (United States)

    Koyama, Tomohide; Hamada, Hirohisa; Nishida, Masamichi; Naess, Paal A; Gaarder, Christine; Sakamoto, Tetsuya

    2016-01-25

    Patients with blunt trauma to the liver have elevated levels of liver enzymes within a short time post injury, potentially useful in screening patients for computed tomography (CT). This study was performed to define the optimal cut-off values for serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in patients with blunt liver injury diagnosed with contrast enhanced multi detector-row CT (CE-MDCT). All patients admitted from May 2006 to July 2013 to Teikyo University Hospital Trauma and Critical Care Center, and who underwent abdominal CE-MDCT within 3 h after blunt trauma, were retrospectively enrolled. Using receiver operating characteristic (ROC) curve analysis, the optimal cut-off values for AST and ALT were defined, and sensitivity and specificity were calculated. Of a total of 676 blunt trauma patients 64 patients were diagnosed with liver injury (Group LI+) and 612 patients without liver injury (Group LI-). Group LI+ and LI- were comparable for age, Revised Trauma Score, and Probability of survival. The groups differed in Injury Severity Score [median 21 (interquartile range 9-33) vs. 17 (9-26) (p tool for CT scan in patients otherwise eligible for observation only or as a transfer criterion to a facility with CT scan capability.

  9. Effect of propylthiouracil on 125I-L-triiodothyronine binding to the nuclei and on malic enzyme activity in rat liver cytosol

    International Nuclear Information System (INIS)

    Knopp, J.

    1980-01-01

    The effects of propylthiouracil (PTU), triiodothyronine (T 3 ) and thyroxine (T 4 ) on the malic enzyme activity of rat liver cytosol and on the binding of 125 I-L-triiodothyronine to the nuclear fraction were examined. A significant decrease in in vitro binding of 125 I-T 3 to the liver nuclei was found in rats fed PTU for 12 h, 24 h and 120 h. The hepatic malic enzyme activity was unchanged after 12 h, but markedly decreased after 24 h and 120 h of PTU treatment. In 120 h PTU fed animals the effect of T 3 on the malic enzyme activity was five times higher in comparison with an equimolar dose of T 4 . Finally, the effect of T 4 on the malic enzyme activity was observed which might result from the intrinsic activity of T 4 under the conditions of a decreased T 4 to T 3 conversion due to the PTU feeding. The obtained results show that there is a certain correlation between the nuclear T 3 binding and the cytosol malic enzyme activity which is presumably induced directly through the m-RNA synthesis stimulated by thyroid hormones. (author)

  10. Atorvastatin induces bile acid-synthetic enzyme Cyp7a1 by suppressing FXR signaling in both liver and intestine in mice[S

    Science.gov (United States)

    Fu, Zidong Donna; Cui, Julia Yue; Klaassen, Curtis D.

    2014-01-01

    Statins are effective cholesterol-lowering drugs to treat CVDs. Bile acids (BAs), the end products of cholesterol metabolism in the liver, are important nutrient and energy regulators. The present study aims to investigate how statins affect BA homeostasis in the enterohepatic circulation. Male C57BL/6 mice were treated with atorvastatin (100 mg/kg/day po) for 1 week, followed by BA profiling by ultra-performance LC-MS/MS. Atorvastatin decreased BA pool size, mainly due to less BA in the intestine. Surprisingly, atorvastatin did not alter total BAs in the serum or liver. Atorvastatin increased the ratio of 12α-OH/non12α-OH BAs. Atorvastatin increased the mRNAs of the BA-synthetic enzymes cholesterol 7α-hydroxylase (Cyp7a1) (over 10-fold) and cytochrome P450 27a1, the BA uptake transporters Na+/taurocholate cotransporting polypeptide and organic anion transporting polypeptide 1b2, and the efflux transporter multidrug resistance-associated protein 2 in the liver. Noticeably, atorvastatin suppressed the expression of BA nuclear receptor farnesoid X receptor (FXR) target genes, namely small heterodimer partner (liver) and fibroblast growth factor 15 (ileum). Furthermore, atorvastatin increased the mRNAs of the organic cation uptake transporter 1 and cholesterol efflux transporters Abcg5 and Abcg8 in the liver. The increased expression of BA-synthetic enzymes and BA transporters appear to be a compensatory response to maintain BA homeostasis after atorvastatin treatment. The Cyp7a1 induction by atorvastatin appears to be due to suppressed FXR signaling in both the liver and intestine. PMID:25278499

  11. Adrenal Insufficiency as a Cause of Acute Liver Failure: A Case Report

    Directory of Open Access Journals (Sweden)

    Jamshid Vafaeimanesh

    2013-01-01

    Full Text Available Introduction. Many diseases and conditions can contribute to elevated liver enzymes. Common causes include viral and autoimmune hepatitis, fatty liver, and bile duct diseases, but, in uncommon cases like liver involvement in endocrine disorders, liver failure is also seen. Adrenal insufficiency is the rarest endocrine disorder complicating the liver. In the previously reported cases of adrenal insufficiency, mild liver enzymes elevation was seen but we report a case with severe elevated liver enzymes and liver failure due to adrenal insufficiency. Based on our knowledge, this is the first report in this field. Case Report. A 39-year-old woman was referred to emergency ward due to drowsiness and severe fatigue. Her laboratory tests revealed prothrombin time: 21 sec, alanine aminotransferase (ALT: 2339 IU/L, aspartate aminotransferase (AST: 2002 IU/L, and ALP: 90 IU/L. No common cause of liver involvement was discovered, and eventually, with diagnosis of adrenal insufficiency and corticosteroid therapy, liver enzymes and function became normal. Finally, the patient was discharged with good general condition. Conclusion. With this report, we emphasize adrenal insufficiency (primary or secondary as a reason of liver involvement in unexplainable cases and recommend that any increase in the liver enzymes, even liver failure, in these patients should be observed.

  12. Effect of Vitamin B5 on Liver Enzyme Levels in Bile Duct Ligation Cholestatic Rat Model

    Directory of Open Access Journals (Sweden)

    Fatemeh Sadat Emami

    2017-01-01

    Full Text Available Background and Objectives: Accumulation of toxic bile salts in a bile duct ligation (BDL animal model plays a pivotal role in the induction of liver fibrosis. Vitamin B5 is an essential nutrient, which acts as a cofactor in many detoxification system enzymes. In the present research, the antifibrotic effect of vitamin B5 was investigated on liver cholestasis induced by BDL in rats. Methods: In this experimental study, 72 male Wistar rats were divided into 9 groups: Control, sham-operated, vitamin B5 (5, 50, and 100mg/kg bw, BDL, and BDL+vitamin B5 (5, 50, and 100mg/kg bw. After BDL, rats were given vitamin B5 via intragastric gavage for 28 consecutive days. At the end of the experiment, blood was collected from heart and activity of aspartate aminotransferase (AST, alanine aminotransferase (ALT, and alkaline phosphatase (ALP enzymes, were measured. The data were analyzed using one-way ANOVA test. Results: In the BDL animals, the serum activities of AST, ALT, and ALP significantly increased (p<0.001. Treatment of BDL rats with vitamin B5 significantly attenuated these changes. Conclusion: The results of this study indicated that vitamin B5 has hepatoprotective and antifibrotic effects in the cholestatic liver, which is likely due to the antioxidative and free radical scavenging effects of this vitamin.

  13. Evaluation of liver marker enzymes in diabetic subjects in the ...

    African Journals Online (AJOL)

    The activity levels of the liver marker enzymes; Aspartate and Alanine amino transferases (AST and ALT), Alkaline Phosphatase (ALP) and Gamma glutamyltransferase (GGT) in diabetic and non-diabetic subjects within the ages of 25 to 86 were assayed. This study was for two weeks. The results indicated that the plasma ...

  14. Liver enzymes in diabetic and non diabetic subjects with clinically diagnosed hepatitis

    Directory of Open Access Journals (Sweden)

    Bidhan Chandra Sarkar

    2011-07-01

    Full Text Available The occurrence of liver disease and raised liver enzymes is common in diabetic patients and the increasing level of enzymes indicates the severity of hepatic injury. Very few studies have addressed this issue in Bangladesh though Bangladeshi population is very much susceptible to diabetes. This study investigated a total of 1400 diabetic patients and 100 non diabetic individuals to compare the level of liver enzymes between diabetic and non-diabetic subjects. The comparisons were made among subjects who were referred to the department of Gastro-hepato-pancreatic diseases (GHPD of BIRDEM with the clinical diagnosis of chronic hepatitis and other gastro-intestinal disorders. The investigations included alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP and bilirubin levels. The subjects were categorized with and without hepatitis based on these investigations. The biochemical markers (ALT, AST, ALP, bilirubin did not differ significantly between non-diabetic male and female subjects. Neither the differences were significant between diabetic males and females though the diabetic patients had higher level of markers. In contrast, when compared between diabetic and non-diabetic subjects there were striking differences in either sex. Compared with the non-diabetic the diabetic subjects had significantly higher level of ALT (48.3 vs. 277.0, AST (42.0 vs. 213.0 and ALP (148 vs. 302 in males (p<0.005 for all. Similarly, these values were found significantly higher in diabetic females than their non-diabetic counterparts (p<0.01. For bilirubin, it was also found significant in males (p<0.001. The study revealed that the liver enzymes were found elevated in both diabetic and non-diabetic subjects who were referred with clinically diagnosed hepatitis. The enzymes were found markedly elevated among the diabetic than non diabetic patients, which indicate hepatic injury was more marked among the diabetic patients. Further

  15. Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

    International Nuclear Information System (INIS)

    Perrone, Carmen E.; Duan, Jian Dong; Jeffrey, Alan M.; Williams, Gary M.; Ahr, Hans-Juergen; Schmidt, Ulrich; Enzmann, Harald H.

    2004-01-01

    Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovoturkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using 32 P-postlabeling for DNA adducts. In ovoexposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had 32 P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity. (orig.)

  16. Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Perrone, Carmen E.; Duan, Jian Dong; Jeffrey, Alan M.; Williams, Gary M. [New York Medical College, Department of Pathology, Valhalla (United States); Ahr, Hans-Juergen; Schmidt, Ulrich [Bayer AG, Institute of Toxicology, Wuppertal (Germany); Enzmann, Harald H. [Federal Institute for Drugs and Medical Devices, Bonn (Germany)

    2004-10-01

    Avian embryos are a potential alternative model for chemical toxicity and carcinogenicity research. Because the toxic and carcinogenic effects of some chemicals depend on bioactivation, activities of biotransformation enzymes and formation of DNA adducts in embryonic turkey liver were examined. Biochemical analyses of 22-day in ovoturkey liver post-mitochondrial fractions revealed activities of the biotransformation enzymes 7-ethoxycoumarin de-ethylase (ECOD), 7-ethoxyresorufin de-ethylase (EROD), aldrin epoxidase (ALD), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronyltransferase (GLUT). Following the administration of phenobarbital (24 mg/egg) on day 21, enzyme activities of ECOD, EROD, ALD, EH and GLUT, but not of GST, were increased by two-fold or higher levels by day 22. In contrast, acute administration of 3-methylcholanthrene (5 mg/egg) induced only ECOD and EROD activities. Bioactivation of structurally diverse pro-carcinogens was also examined using {sup 32}P-postlabeling for DNA adducts. In ovoexposure of turkey embryos on day 20 of gestation to 2-acetylaminofluorene (AAF), 4,4'-methylenebis(2-chloroaniline) (MOCA), benzo[a]pyrene (BaP), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) resulted in the formation of DNA adducts in livers collected by day 21. Some of the DNA adducts had {sup 32}P-postlabeling chromatographic migration patterns similar to DNA adducts found in livers from Fischer F344 rats exposed to the same pro-carcinogens. We conclude that 21-day embryonic turkey liver is capable of chemical biotransformation and activation of genotoxic carcinogens to form DNA adducts. Thus, turkey embryos could be utilized to investigate potential chemical toxicity and carcinogenicity. (orig.)

  17. Enzyme immunoassay of oestrogen receptors in needle biopsies from human liver

    DEFF Research Database (Denmark)

    Becker, U; Andersen, J; Poulsen, H S

    1991-01-01

    For quantitative assessments of sex hormone receptors in liver tissue, ligand binding assays are inconvenient, as they require large biopsies (0.5-1.0 g). The present study shows that it is possible to measure oestrogen receptors (ER) quantitatively in needle biopsy specimens as small as 10 mg...... by modifications of a commercial enzyme immunoassay employing monoclonal antibodies. Sucrose gradient centrifugation and the dextran charcoal method served as reference methods. A consecutive series of needle biopsies from patients suspected of liver disease were investigated. The biopsies (n = 37) had a median...

  18. Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

    OpenAIRE

    Liu, Junxi; Au Yeung, Shiu Lun; Lin, Shi Lin; Leung, Gabriel M.; Schooling, C. Mary

    2016-01-01

    We used Mendelian randomization to estimate the causal effects of the liver enzymes, alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma glutamyltransferase (GGT), on diabetes and cardiovascular disease, using genetic variants predicting these liver enzymes at genome wide significance applied to extensively genotyped case-control studies of diabetes (DIAGRAM) and coronary artery disease (CAD)/myocardial infarction (MI) (CARDIoGRAMplusC4D 1000 Genomes). Genetically higher ALT ...

  19. Quantitative aspects of enzyme histochemistry on sections of freeze-substituted glycol methacrylate-embedded rat liver

    NARCIS (Netherlands)

    Frederiks, W. M.; Bosch, K. S.

    1993-01-01

    Freeze-substituted rat liver embedded in glycol methacrylate (GMA) has been used to demonstrate the activities of several enzymes. The following enzymes could be detected in GMA-sections by the indicated histochemical procedure(s): 5'-nucleotidase (lead salt, cerium-diaminobenzidine), alkaline

  20. The Effect of Chlorella vulgaris Supplementation on Liver Enzymes, Serum Glucose and Lipid Profile in Patients with Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Mehrangiz Ebrahimi-Mameghani

    2014-07-01

    Full Text Available Background: Non-alcoholic fatty liver disease (NAFLD is becoming a public health problem worldwide and using microalgae is a new approach on its treatment. The aim of this study was to investigate the effect of Chlorella vulgaris supplementation on liver enzymes, serum glucose and lipid profile in patients with NAFLD. Methods: This double-blind randomized placebo-controlled clinical trial was conducted on 60 NAFLD patients from specialized clinics of Tabriz University of Medical Sciences from December 2011 to July 2012. The subjects were randomly allocated into 2 groups: 1 “intervention” (n=30 received 400 mg/day vitamin E plus four 300 mg tablets of Chlorella vulgaris and, 2 “placebo” (n=30 received 400 mg/day vitamin E and four placebo tablets per day for 8 weeks. Weight, liver enzymes and metabolic factors were assessed in fasting serum and dietary data was collected at baseline and end of the study. Results: Weight, liver enzymes, fasting blood sugar (FBS and lipid profile decreased significantly in both groups (P<0.05. The differences in weight, ALP and FBS between the two groups were statistically significant (P=0.01, P=0.04 and P=0.02, respectively. Conclusion: C. vulgaris seems to improve FBS and lipid profile and therefore could be considered as an effective complementary treatment in NAFLD.

  1. Investigation of the associations between low-dose serum perfluorinated chemicals and liver enzymes in US adults.

    Science.gov (United States)

    Lin, Chien-Yu; Lin, Lian-Yu; Chiang, Chih-Kang; Wang, Wei-Jie; Su, Yi-Ning; Hung, Kuan-Yu; Chen, Pau-Chung

    2010-06-01

    Perfluorinated chemicals (PFCs) have been largely used for years in a variety of products worldwide. However, the toxic effect of PFCs on exposure to the liver in the general population has not yet been determined. In this study, 2,216 adults (18 years of age or older) were recruited in a National Health and Nutrition Examination Survey (NHANES) in 1999-2000 and 2003-2004 to determine the relationship between serum level of PFCs and the levels of liver enzymes. The data were adjusted for all other confounding variants. After performing mathematical analysis, we determined when serum log-perfluorooctanoic acid (PFOA) increases in one unit, the serum alanine aminotransferase (ALT) concentration (U/l) increases by 1.86 units (95% confidence interval (CI), 1.24-2.48; P=0.005), and the serum log-gamma-glutamyltransferase (GGT) concentration (U/l) is 0.08 unit higher (95% CI, 0.05-0.11; P=0.019). The association between PFOA and liver enzymes was more evident in obese subjects, as well as subjects with insulin resistance and/or metabolic syndromes. When dividing the serum PFOA into quartiles in the fully adjusted models in subjects with a body mass index>or=30 kg/m2, the ALT level trend across the serum PFOA quartiles was significant (P=0.003). On the basis of these data, we conclude that a higher serum concentration of PFOA may cause liver enzymes to increase abnormally in the general population, particularly in obese individuals. Further studies are warranted to clarify the casual relationship between PFCs and these liver enzymes.

  2. Potential role of liver enzymes levels as predictor markers of glucose metabolism disorders in Tunisian population.

    Science.gov (United States)

    Bouhajja, Houda; Abdelhedi, Rania; Amouri, Ali; Hadj Kacem, Faten; Marrakchi, Rim; Safi, Wajdi; Mrabet, Houcem; Chtourou, Lassaad; Charfi, Nadia; Fourati, Mouna; Bensassi, Salwa; Jamoussi, Kamel; Abid, Mohamed; Ayadi, Hammadi; Feki, Mouna Mnif; Elleuch, Noura Bougacha

    2018-03-10

    The relationship between liver enzymes and type 2 diabetes (T2D) risk is inconclusive. We aimed to evaluate the association between liver markers and risk of carbohydrate metabolism disorders and their discriminatory power for T2D prediction. This cross-sectional study enrolled 216 participants classified as normoglycemic, prediabetes, newly-diagnosed diabetes and diagnosed diabetes. All participants underwent anthropometric and biochemical measurements. The relationship between hepatic enzymes and glucose metabolism markers was evaluated by ANCOVA analyses. The associations between liver enzymes and incident carbohydrate metabolism disorders were analyzed through logistic regression and their discriminatory capacity for T2D by receiver operating characteristic (ROC) analysis. High alkaline phosphatase (AP), alanine aminotransferase (ALT), γ-glutamyltransferase (γGT) and aspartate aminotrasferase (AST) levels were independently related to decreased insulin sensitivity. Interestingly, higher AP level was significantly associated with increased risk of prediabetes (p=0.017), newly-diagnosed diabetes (p=0.004) and T2D (p=0.007). Elevated γGT level was an independent risk factor for T2D (p=0.032) and undiagnosed-T2D (p=0.010) in prediabetic and normoglycemic subjects, respectively. In ROC analysis, AP was a powerful predictor of incident diabetes and significantly improved T2D prediction. Liver enzymes within normal range, specifically AP levels, are associated with increased risk of carbohydrate metabolism disorders and significantly improved T2D prediction.

  3. Effect of pH 5 enzyme from liver on the protein synthesis by mammary gland subcellular fractions in vitro

    International Nuclear Information System (INIS)

    Singh, Jaspal; Singh, Ajit; Ganguli, N.C.

    1976-01-01

    The effect of pH 5 enzyme fraction of liver on the protein synthesizing activity of the subcellular fractions of the mammary gland has been investigated. Results indicate that (1) lactating liver pH 5 enzyme stimulates protein synthesis which is enhanced by the addition of ATP-generating system and (2) the enzyme fractions from the non-lactating liver inhibits the protein synthesis by mammary fractions, but in some cases like mitochondrial and supernatant fractions of mammary it elevates the synthesis when supplemented with ATP-generating system. Chlorella protein hydrolysate- 14 C was used as a tracer and rabits were used as experimental animals. (M.G.B.)

  4. Profile of liver enzymes in non-alcoholic fatty liver disease in patients with impaired glucose tolerance and newly detected untreated type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Debmalya Sanyal

    2015-01-01

    Full Text Available Context: The perception of non-alcoholic fatty liver disease (NAFLD as an uncommon and benign condition is rapidly changing. Approximately, 70% type 2 diabetes mellitus (T2DM patients have a fatty liver, which may follow an aggressive course with necroinflammation and fibrosis. Aims: To assess the profile of liver enzymes in subjects with impaired glucose tolerance (IGT, new onset treatment naive T2DM and normal glucose tolerance (NGT with and without NAFLD. Settings and Design: Cross-sectional clinic-based study. Subjects and Methods: 152 IGT and 158 recently detected T2DM subjects aged between 30 and 69 years, along with 160 age and gender matched controls with NGT. An ultrasonography scan of the upper abdomen was done in all patients in order to examine presence of fatty liver. Anthropometry, lipid profile, liver enzymes were also analyzed in all patients. Statistical Analysis Used: Unpaired t-test, Chi-square/Fisher Exact test (for categorical variables, Pearson/Spearmen correlation test to find significant difference, association and correlation between two or more groups respectively. Results: NAFLD was significantly associated with higher alanine aminotransferase (ALT and gamma-glutamyl transferase (GGT but not ALP levels in IGT and T2DM patients. ALT, GGT significant correlated with waist circumference, body mass index, fasting insulin, homeostatic model assessment- insulin resistance, fasting blood glucose, high density lipoprotein cholesterol, triglyceride. 57% of NAFLD patients had normal ALT between 25 and 40 U/L, 53% of NAFLD subjects had normal GGT between 15 and 30 U/L. ALT 40 U/L and GGT > 30 U/L had highest positive predictivity for presence of NAFLD in our study sample. Conclusions: Mild elevations of liver enzymes in the upper normal range are associated with features of metabolic syndrome and NAFLD even in IGT and recently detected T2DM patients. Novel cut-offs for liver enzymes are warranted in order to prevent unnecessary

  5. Posttraumatic levels of liver enzymes can reduce the need for CT in children

    DEFF Research Database (Denmark)

    Bruhn, Peter James; Østerballe, Lene; Hillingsø, Jens

    2016-01-01

    alternative diagnostic modalities. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are hepatic enzymes, which are elevated in peripheral blood in relation to liver injury. The aim of the present study was to investigate a potential role of normal liver transaminase levels in the decision......BACKGROUND: Computed tomography (CT) is the gold standard in the initial evaluation of the hemodynamically stable patient with suspected liver trauma. However, the adverse effects of radiation exposure are of specific concern in the pediatric population. It is therefore desirable to explore...... algorithm in suspected pediatric blunt liver trauma. METHODS: Retrospective analysis of consecutively collected data from children (0-17 years) with blunt liver trauma, admitted to a single trauma centre in Denmark, between 2000 and 2013. Patients underwent abdominal CT during initial evaluation...

  6. Correlation of Endothelin-1 Concentration and Angiotensin-Converting Enzyme Activity with the Staging of Liver Fibrosis

    OpenAIRE

    Kardum, Duško; Fabijanić, Damir; Lukić, Anita; Romić, Željko; Petrovečki, Mladen; Bogdanović, Zoran; Jurić, Klara; Urek-Crnčević, Marija; Banić, Marko

    2012-01-01

    Increased serum angiotensin-converting enzyme (SACE) activity and serum concentration of endothelin-1 (ET-1) were found in liver cirrhosis. We investigated a correlation between the different stages of liver fibrosis and SACE activity and serum ET-1 concentration. Seventy patients with pathohistologically established chronic liver disease were divided in three groups according to Ishak criteria for liver fibrosis: minimal fibrosis (Ishak score 0–1, n=20), medium fibrosis (Ishak sc...

  7. The effect of steroidal contraceptives on liver enzymes and serum ...

    African Journals Online (AJOL)

    This study assessed the influence of steroidal contraceptives on liver enzymes and serum total protein using 48 adult female rats in four groups -A as control and B, C and D as tests. The animals were further divided into two subgroups - treatment (A1 - D1; n=6 each) and reversal (A2 - D2; n=6 each). Groups A1&A2 ...

  8. ENZYME MARKERS ACTIVITY AND BILE FORMATION FUNCTION OF LIVER IN CASES OF TUBERCULOSTATICS AND HEXAVALENT CHROMIUM COMPOUNDS AFFECTION IN RATS

    Directory of Open Access Journals (Sweden)

    N. I. Burmas

    2016-05-01

    Full Text Available Background. Currently, the growing incidence of toxic lesions of the liver is associated with industrial chemicalization and uncontrolled use of hepatotoxic drugs in everyday life. There are about one thousand drugs with high or low hepatotoxicity, such as anti-TB drugs. Objective. In this research we studied the intracellular enzymes activity and bile formation function of the liver in rats of different ages in cases of tuberculostatic (isoniazid and rifampicin affection and chromium (potassium dichromate intoxication. Methods. The experimental affection of rats of different ages was performed by combined injection of hexavalent chromium compounds (a solution of potassium dichromate, 3 mg/kg, isoniazid (0.05 g/kg and rifampicin (0.25 g/kg. On the 7th and 14th days the rats were injected with enterosorbent Sorbex (150 mg/kg. Enzyme markers activity of the liver was evaluated due to alanine and aspartate aminotransferases (ALT and AST and alkaline phosphatase (ALP rates. Bile formation function of the liver was evaluated by total bilirubin and bile acids content in blood. Results. The disorders in hepatocytes plasma membranes permeability were defined by the increased rates of ALT, AST and alkaline phosphatase in blood serum which were decreased in the liver. It was determined that total bilirubin and bile acids content in blood serum of the affected animals increased. It influenced hepatocytes excretion in bile capillaries and caused cholestasis and revenues decrease in bile. Conclusions. The most significant metabolic disorders in cases of chrome-isoniazid-rifampicin affection were defined in immature and senior animals in comparison with mature animals.

  9. First Trimester Hemolysis, Elevated Liver Enzymes, Low Platelets Syndrome in a Surrogate Pregnancy.

    Science.gov (United States)

    Myer, Emily; Hill, James

    2015-10-01

    Background The occurrence of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 20 weeks of gestation is rare. HELLP is a possible but rare syndrome in gestational surrogate pregnancies for surrogates with risk factors for development of preeclampsia. Case A 32-year-old patient with chronic hypertension and positive antinuclear antibody presented for prenatal care at 13 weeks and 1 day. She was a surrogate for the embryo of a 43-year-old couple. By 15 weeks she developed uncontrolled hypertension requiring hospitalization. She was expectantly managed until her condition deteriorated. At 16 weeks and 1 day she developed hemolysis, elevated liver enzymes, thrombocytopenia, and fetal demise. Conclusions HELLP syndrome is rare and carries a significant morbidity and mortality for the mother and fetus. Clinicians should encourage the surrogate to share her medical history with the embryo donor for appropriate counseling on pregnancy risks.

  10. Relationships among alcoholic liver disease, antioxidants, and antioxidant enzymes.

    Science.gov (United States)

    Han, Kyu-Ho; Hashimoto, Naoto; Fukushima, Michihiro

    2016-01-07

    Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide. The metabolism of ethanol generates reactive oxygen species, which play a significant role in the deterioration of alcoholic liver disease (ALD). Antioxidant phytochemicals, such as polyphenols, regulate the expression of ALD-associated proteins and peptides, namely, catalase, superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase. These plant antioxidants have electrophilic activity and may induce antioxidant enzymes via the Kelch-like ECH-associated protein 1-NF-E2-related factor-2 pathway and antioxidant responsive elements. Furthermore, these antioxidants are reported to alleviate cell injury caused by oxidants or inflammatory cytokines. These phenomena are likely induced via the regulation of mitogen-activating protein kinase (MAPK) pathways by plant antioxidants, similar to preconditioning in ischemia-reperfusion models. Although the relationship between plant antioxidants and ALD has not been adequately investigated, plant antioxidants may be preventive for ALD because of their electrophilic and regulatory activities in the MAPK pathway.

  11. Acute Liver Failure Due to Regorafenib May Be Caused by Impaired Liver Blood Flow: A Case Report.

    Science.gov (United States)

    Akamine, Takaki; Ando, Koji; Oki, Eiji; Saeki, Hiroshi; Nakashima, Yuichiro; Imamura, Y U; Ohgaki, Kippei; Maehara, Yoshihiko

    2015-07-01

    Regorafenib has been approved for treatment of patients with unresectable or recurrent gastrointestinal stromal tumors resistant to imatinib or sunitinib. However, regorafenib has severe side-effects, including acute liver failure. We describe the case of a patient with multiple liver metastases of a small intestinal stromal tumor who experienced acute liver failure while being treated with regorafenib. A 50-year-old patient with an unresectable small intestinal stromal tumor resistant to prior treatment with imatinib and sunitinib was started on regorafenib, but experienced acute liver failure 10 days later. Plasma exchange and steroid pulse treatment improved her liver function. During liver failure, abdominal ultrasonography showed to-and-fro flow in the portal vein. Lactate dehydrogenase concentration was markedly elevated to 1633 U/l. These findings indicate that liver failure in this patient was due to impaired liver blood flow. Regorafenib may impair liver blood flow, inducing acute liver failure. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Effect of parenteral serum plant sterols on liver enzymes and cholesterol metabolism in a patient with short bowel syndrome.

    Science.gov (United States)

    Hallikainen, Maarit; Huikko, Laura; Kontra, Kirsi; Nissinen, Markku; Piironen, Vieno; Miettinen, Tatu; Gylling, Helena

    2008-01-01

    Hepatobiliary complications are common during parenteral nutrition. Lipid moiety in commercially available solutions contains plant sterols. It is not known whether plant sterols in parenteral nutrition interfere with hepatic function in adults. We detected how different amounts of plant sterols in parenteral nutrition solution affected serum plant sterol concentrations and liver enzymes during a 1.5-year follow-up in a patient with short bowel syndrome. Serum lipid, plant sterol, and liver enzyme levels were measured regularly during the transition from Intralipid (100% soy-based intravenous fat emulsion) to ClinOleic (an olive oil-based intravenous fat emulsion with 80% olive oil, 20% soy oil and lower plant sterols); the lipid supply was also gradually increased from 20 to 35 g/d. Plant sterols in parenteral nutrition solution and serum were measured with gas-liquid chromatography. During infusion of soy-based intravenous fat emulsion (30 g/d, total plant sterols 87 mg/d), the concentrations of sitosterol, campesterol, and stigmasterol were 4361, 1387, and 378 microg/dL, respectively, and serum liver enzyme values were >or= 2.5 times above upper limit of normal. After changing to olive oil-based intravenous fat emulsion (20-35 g/d, plant sterols 37-65 mg/d), concentrations decreased to 2148 to 2251 microg/dL for sitosterol, 569-297 microg/dL for campesterol, and 95-55 microg/dL for stigmasterol. Concomitantly, liver enzyme values decreased to 1.4 to 1.8 times above upper limit of normal at the end of follow-up. The nutrition status of the patient improved. The amount of plant sterols in lipid emulsion affects serum liver enzyme levels more than the amount of lipid.

  13. Gd-EOB-DTPA enhanced MRI of the liver: Correlation of relative hepatic enhancement, relative renal enhancement, and liver to kidneys enhancement ratio with serum hepatic enzyme levels and eGFR

    Energy Technology Data Exchange (ETDEWEB)

    Talakic, Emina; Steiner, Jürgen; Kalmar, Peter; Lutfi, Andre [Division of General Radiology, Department of Radiology, Medical University of Graz, Auenbruggerplatz 9, 8036 Graz (Austria); Quehenberger, Franz [Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Auenbruggerplatz 2, 8036 Graz (Austria); Reiter, Ursula; Fuchsjäger, Michael [Division of General Radiology, Department of Radiology, Medical University of Graz, Auenbruggerplatz 9, 8036 Graz (Austria); Schöllnast, Helmut, E-mail: helmut.schoellnast@medunigraz.at [Division of General Radiology, Department of Radiology, Medical University of Graz, Auenbruggerplatz 9, 8036 Graz (Austria)

    2014-04-15

    Objectives: To assess the correlation of relative hepatic enhancement (RHE), relative renal enhancement (RRE) and liver to kidneys enhancement ratio (LKR) with serum hepatic enzyme levels and eGFR in Gd-EOB-DTPA enhanced MRI of the liver and to assess threshold levels for predicting enhancement of the liver parenchyma. Methods: Data of 75 patients who underwent Gd-EOB-DTPA enhanced MRI of the liver were collected. Images were obtained before contrast injection, during the early arterial phase, late arterial phase, venous phase, delayed phase, and hepatobiliary phase which was 20 min after Gd-EOB-DTPA administration. Signal intensity of the liver and the kidneys in all phases was defined using region-of-interest measurements for relative enhancement calculation. Serum hepatic enzyme levels and eGFR were available in all patients. Spearman correlation test was used to test the correlation of RHE, RRE and LKR with serum hepatic enzyme levels and eGFR. Results: In the hepatobiliary phase all serum hepatic enzymes were significantly correlated with RHE; total bilirubin (TBIL) and cholin esterase (CHE) showed strongest correlations. TBIL and CHE were significantly correlated with RRE in the arterial phases. TBIL and CHE were significantly correlated with LKR in the arterial phase and hepatobiliary phase. eGFR showed no correlation. Conclusions: In Gd-EOB-DTPA enhanced MRI, TBIL and CHE levels may predict RHE, RRE and LKR.

  14. A cross-sectional study of the relationship between serum liver enzymes level and the incidence of impaired fasting glucose in males and females.

    Science.gov (United States)

    Qin, Guangming; Lu, Lihong; Xiao, Yufei; Zhu, Yimiao; Pan, Wensheng; Xu, Xiang; Shen, Shengrong; Das, Undurti N

    2014-07-28

    The aim of this study was to investigate the possible correlation between levels of serum liver enzymes and impaired fasting glucose (IFG) in Chinese adults and to provide a new perspective for the prevention of pre-diabetes. Serum liver enzymes of the samples including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and g-glutamyl transferase (GGT), as well as plasma glucose, blood lipids, and insulin, were measured. The cumulative incidences of IFG between different quartiles of liver enzymes were compared by the chi-square test. A logistic regression model (binary regression) was used to calculate the odds ratio (OR) of IFG with 95% confidence interval (95% CI). The total incidence of IFG was 20.3% and the cumulative incidence of IFG was higher in men compared to women. In both sexes, IFG is more prevalent in higher quartiles of liver enzymes. After adjusting for age, BMI, blood pressure, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC), the cumulative incidences of IFG were significantly higher in the highest quartiles of liver enzymes than in the lowest quartiles. A significantly higher cumulative incidence of IFG was found in the highest GGT quartile than in the lowest quartile for woman. The results of this study suggest that serum liver enzymes are related to the risk of IFG in Chinese adults. We infer that preserving the hepatic function may be an efficient way to prevent the development of IFG, especially in males.

  15. [Effect of low-intensity 900 MHz frequency electromagnetic radiation on rat liver and blood serum enzyme activities].

    Science.gov (United States)

    Nersesova, L S; Petrosian, M S; Gazariants, M G; Mkrtchian, Z S; Meliksetian, G O; Pogosian, L G; Akopian, Zh I

    2014-01-01

    The comparative analysis of the rat liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and purine nucleoside phosphorylase post-radiation activity levels after a total two-hour long single and fractional exposure of the animals to low-intensity 900 MHz frequency electromagnetic field showed that the most sensitive enzymes to the both schedules of radiation are the liver creatine kinase, as well as the blood serum creatine kinase and alkaline phosphatase. According to the comparative analysis of the dynamics of changes in the activity level of the liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase and purine nucleoside phosphorylase, both single and fractional radiation schedules do not affect the permeability of a hepatocyte cell membrane, but rather cause changes in their energetic metabolism. The correlation analysis of the post-radiation activity level changes of the investigated enzymes did not reveal a clear relationship between them. The dynamics of post-radiation changes in the activity of investigated enzyme levels following a single and short-term fractional schedules of radiation did not differ essentially.

  16. The effect of ZnO Nps of 20 nm on changes of enzyme and liver tissues of pregnant NMRI mice

    Directory of Open Access Journals (Sweden)

    bager Seyed Alipour

    2015-01-01

    Full Text Available Background :Nowadays, nanotechnology has been developing rapidly and may have considerable effects on industry, society and the environment. In this research the toxicity properties of zinc oxide nanoparticles with a size of 20 nm on enzyme and liver tissue of NMRI mice were studied. Materials and Methods: This experimental study was performed in standard conditions on 25 NMRI mice with an average weight of 30 ± 3 g so that they received different doses of zinc oxide nanoparticles, an a days, for 15 days intraperitoneally. Then, blood samples were taken on day 17 of NMRI mice. The collected tissues were washed with saline and fixed in Boin΄s fluied buffer and stained with hematoxylin and eosin for histopathology evaluation. After data collection, statistical analysis was done using SAS software. Results: The results showed that activity of ALT enzyme at concentrations 50, 100, 150 and 200 mg/kg ZnO Nps at a significant level (p<0.05 increased in comparison with the control group. Histopathological investigation showed that zinc oxide nanoparticles caused severe damage in liver. Damaged liver cells develop leaky membranes and escape of intracellular enzymes into the bloodstream. Conclusion: Our findings showed that using different concentration of zinc oxide nanoparticles could be caused undesirable effects on liver with damage to hepatocyte and level elevation of liver enzymes.

  17. Cerebral blood flow and liver function in patients with encephalopathy due to acute and chronic liver diseases

    DEFF Research Database (Denmark)

    Almdal, T; Schroeder, T; Ranek, L

    1989-01-01

    The purpose of the present investigation was to study changes in cerebral blood flow (CBF) in hepatic encephalopathy, to ascertain whether this was related to the changes in liver function and whether these changes gave any prognostic information. CBF, determined by the intravenous xenon-133 method......, and liver functions, assessed by the prothrombin index, bilirubin concentration, and the galactose elimination capacity, were studied in patients with acute fulminant liver failure and in patients with encephalopathy due to chronic liver diseases--that is, cirrhosis of various etiologies. The CBF range...

  18. 2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections.

    Science.gov (United States)

    Tasdemir, Deniz; Sanabria, David; Lauinger, Ina L; Tarun, Alice; Herman, Rob; Perozzo, Remo; Zloh, Mire; Kappe, Stefan H; Brun, Reto; Carballeira, Néstor M

    2010-11-01

    Acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. In this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (HDAs) and evaluated their in vitro activity against erythrocytic (blood) stages of Plasmodium falciparum and liver stages of Plasmodium yoelii infections. Since the type II fatty acid biosynthesis pathway (PfFAS-II) has recently been shown to be indispensable for liver stage malaria parasites, the inhibitory potential of the HDAs against multiple P. falciparum FAS-II (PfFAS-II) elongation enzymes was also evaluated. The highest antiplasmodial activity against blood stages of P. falciparum was displayed by 5-HDA (IC(50) value 6.6 μg/ml), whereas the 2-HDA was the only acid arresting the growth of liver stage P. yoelii infection, in both flow cytometric assay (IC(50) value 2-HDA 15.3 μg/ml, control drug atovaquone 2.5 ng/ml) and immunofluorescence analysis (IC(50) 2-HDA 4.88 μg/ml, control drug atovaquone 0.37 ng/ml). 2-HDA showed the best inhibitory activity against the PfFAS-II enzymes PfFabI and PfFabZ with IC(50) values of 0.38 and 0.58 μg/ml (IC(50) control drugs 14 and 30 ng/ml), respectively. Enzyme kinetics and molecular modeling studies revealed valuable insights into the binding mechanism of 2-HDA on the target enzymes. All HDAs showed in vitro activity against Trypanosoma brucei rhodesiense (IC(50) values 3.7-31.7 μg/ml), Trypanosoma cruzi (only 2-HDA, IC(50) 20.2 μg/ml), and Leishmania donovani (IC(50) values 4.1-13.4 μg/ml) with generally low or no significant toxicity on mammalian cells. This is the first study to indicate therapeutic potential of HDAs against various parasitic protozoa. It also points out that the malarial liver stage growth inhibitory effect of the 2-HDA may be promoted via PfFAS-II enzymes. The lack of cytotoxicity, lipophilic nature, and calculated pharmacokinetic properties suggests that 2-HDA could be a useful compound to

  19. 2-Hexadecynoic Acid Inhibits Plasmodial FAS-II Enzymes and Arrest Erythrocytic and Liver Stage Plasmodium Infections

    Science.gov (United States)

    Tasdemir, Deniz; Sanabria, David; Lauinger, Ina L.; Tarun, Alice; Herman, Rob; Perozzo, Remo; Zloh, Mire; Kappe, Stefan H.; Brun, Reto; Carballeira, Néstor M.

    2010-01-01

    Acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. In this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (HDAs) and evaluated their in vitro activity against erythrocytic (blood) stages of Plasmodium falciparum and liver stages of P. yoelii infections. Since the type II fatty acid biosynthesis pathway (PfFAS-II) has recently been shown to be indispensable for liver stage malaria parasites, the inhibitory potential of the HDAs against multiple P. falciparum FAS-II (PfFAS-II) elongation enzymes was also evaluated. The highest antiplasmodial activity against blood stages of P. falciparum was displayed by 5-HDA (IC50 value 6.6. μg/ml), whereas the 2-HDA was the only acid arresting the growth of liver stage P. yoelii infection, in both flow cytometric assay (IC50 value 2-HDA 15.3 μg/ml, control drug atovaquone 2.5 ng/ml) and immunofluorescense analysis (IC50 2-HDA 4.88 μg/ml, control drug atovaquone 0.37 ng/ml). 2-HDA showed the best inhibitory against the PfFAS-II enzymes PfFabI and PfFabZ with IC50 values of 0.38 and 0.58 μg/ml (IC50 control drugs 14 and 30 ng/ml) respectively. Enzyme kinetics and molecular modeling studies revealed valuable insights into the binding mechanism of 2-HDA on the target enzymes. All HDAs showed in vitro activity against Trypanosoma brucei rhodesiense (IC50 values 3.7–31.7 μg/ml), Trypanosoma cruzi (only 2-HDA, IC50 20.2 μg/ml), and Leishmania donovani (IC50 values 4.1–13.4 μg/ml) with generally low or no significant toxicity on mammalian cells. This is the first study to indicate therapeutic potential of HDAs against various parasitic protozoa. It also points out that the malarial liver stage growth inhibitory effect of the 2-HDA may be promoted via PfFAS-II enzymes. The lack of cytotoxicity, lipophilic nature and calculated pharmacokinetic properties suggest that 2-HDA could be a useful compound to study the interaction of fatty

  20. Effect of Electromagnetic Waves Generated by Base Transiver Station on Liver Enzymes in Female Rats

    Directory of Open Access Journals (Sweden)

    Gholam-Ali Jelodar

    2013-07-01

    Full Text Available Background: This study was investigating the effect of electromagnetic wave generated by mobile and base transceiver station (900 MHz on liver enzymes in both mature and immature female age.Materials and Methods: In this study, 20 rats Sprague Dawley white mature female age 8 to 9 weeks and weight 180 to 200 g and 20 rats immature age 3 to 4 weeks, weight 80 to 100 g, each age group were randomly divided in two groups (control and test. Test groups, were daily for four hours and four different times exposed to electromagnetic waves with signal generator (900 MHz, 5-meter intervals. Control groups were kept at equal condition (themperature and light in laboratory during experiment. After at the end experimental period, blood was collected by heart puncture of all animal. Exposure to EMF generated by BTS had significant effect on liver enzymes composition in mature and immature rats.Results: AST, ALT and ALP in immature-test groups decreased significantly compared with their respective control groups (p<0.05. ALP in mature-test groups increased significantly compared with their respective control groups (p<0.05.Conclusion: These result suggest that exposure to EMF generated by BTS has a deleterious effect on liver enzymes and that this effect is more sever in immature animals.

  1. The effects of space flight on some rat liver enzymes regulating carbohydrate and lipid metabolism

    Science.gov (United States)

    Abraham, S.; Lin, C. Y.; Klein, H. P.; Volkmann, C.

    1981-01-01

    The effects of space flight conditions on the activities of certain enzymes regulating carbohydrate and lipid metabolism in rat liver are investigated in an attempt to account for the losses in body weight observed during space flight despite preflight caloric consumption. Liver samples were analyzed for the activities of 32 cytosolic and microsomal enzymes as well as hepatic glycogen and individual fatty acid levels for ground control rats and rats flown on board the Cosmos 936 biosatellite under normal space flight conditions and in centrifuges which were sacrificed upon recovery or 25 days after recovery. Significant decreases in the activities of glycogen phosphorylase, alpha-glycerol phosphate acyl transferase, diglyceride acyl transferase, aconitase and 6-phosphogluconate dehydrogenase and an increase in palmitoyl CoA desaturase are found in the flight stationary relative to the flight contrifuged rats upon recovery, with all enzymes showing alterations returning to normal values 25 days postflight. The flight stationary group is also observed to be characterized by more than twice the amount of liver glycogen of the flight centrifuged group as well as a significant increase in the ratio of palmitic to palmitoleic acid. Results thus indicate metabolic changes which may be involved in the mechanism of weight loss during weightlessness, and demonstrate the equivalence of centrifugation during space flight to terrestrial gravity.

  2. Cyclic fatty acid monomers from dietary heated fats affect rat liver enzyme activity.

    Science.gov (United States)

    Lamboni, C; Sébédio, J L; Perkins, E G

    1998-07-01

    This study was conducted to investigate the effects of dietary cyclic fatty acid monomers (CFAM), contained in heated fat from a commercial deep-fat frying operation, on rat liver enzyme activity. A partially hydrogenated soybean oil (PHSBO) used 7 d (7-DH) for frying foodstuffs, or 0.15% methylated CFAM diets was fed to male weanling rats in comparison to a control group fed a nonheated PHSBO (NH) diet in a 10-wk experiment. All diets were isocaloric with 15% fat. Animals fed either CFAM or 7-DH diets showed increased hepatic content of cytochrome (cyt.) b5 and P450 and increased activity of (E.C. 1.6.2.4) NADPH-cyt. P450 reductase in comparison to the control rats. In addition, the activities of (E.C. 2.3.1.21) carnitine palmitoyltransferase-I and (E.C. 1.1.1.42) isocitrate dehydrogenase were significantly decreased when compared to that of rats fed the NH diet. A significantly depressed activity of (E.C. 1.1.1.49) glucose 6-phosphate dehydrogenase was also observed for these animals compared to the control rats fed NH diet. Moreover, liver and microsomal proteins were significantly increased when CFAM or 7-DH diets were fed to animals in comparison to controls while liver glycogen was decreased significantly in experimental groups of rats. The results obtained in this study indicate that the CFAM in the diet from either synthetic sources or used fats increase the activity of liver enzyme systems that detoxify them.

  3. The effects of space flight on some rat liver enzymes regulating carbohydrate and lipid metabolism

    Science.gov (United States)

    Abraham, S.; Lin, C. Y.; Klein, H. P.; Volkmann, C.

    We have examined, in the livers of rats carried aboard the Cosmos 936 biosatellite, the activities of about 30 enzymes concerned with carbohydrate and lipid metabolism. In addition to the enzyme studies, the levels of glycogen and of the individual fatty acids in hepatic lipids were determined. Livers from flight and ground control rats at recovery (R0) and 25 days after recovery (R25) were used for these analyses. For all parameters measured, the most meaningful comparisons are those made between flight stationary (FS) and flight centrifuged (FC) animals at R0. When these two groups of flight rats were compared at R0, statistically significant decreases in the activity levels of glycogen phosphorylase, α-glycerol phosphate acyl transferase, diglyceride acyl transferase, aconitase and 6-phosphogluconate dehydrogenase and an increase in the palmitoyl CoA desaturase were noted in the weightless group (FS). The significance of these findings was strengthened by the fact that all enzyme activities showing alterations at R0 returned to normal 25 days postflight. When liver glycogen and total fatty acids of the two sets of flight animals were determined, significant differences that could be attributed to reduced gravity were observed. The weightless group (FS) at R0 contained, on the average, more than twice the amount of glycogen than did the centrifuged controls (FC) and a remarkable shift in the ratio of palmitate to palmitoleate was noted. These metabolic alterations, both in enzyme levels and in hepatic constituents, appear to be characteristic of the weightless condition. Our data seem to justify the conclusion that centrifugation during flight is equivalent to terrestrial gravity.

  4. Alcohol Prices and Mortality Due to Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Jon P. Nelson

    2015-06-01

    Full Text Available This study estimates a reduced-form regression model for mortality rates due to alcoholic liver diseases, with alcohol prices and income as explanatory variables. Panel data cover the years 2000-2010 for 21 member countries of the European Union. In the reduced form, prices affect mortality rates indirectly through the demand for alcohol, while income has potential direct and indirect effects. Country and time fixed effects are used to control for other factors that influence alcohol consumption and mortality. Special attention is paid to outliers in the data, and final results are based on the MS-estimator for robust regressions. Regression results for alcohol prices and income are sensitive to adjustments for stationary data and down-weighting of outliers and other influential data points. Final results indicate that alcohol prices do not affect mortality rates due to chronic liver diseases. Empirical results in the study do not lend support to broad price-based approaches to alcohol policy.

  5. Single administration of recombinant IL-6 restores the gene expression of lipogenic enzymes in liver of fasting IL-6-deficient mice

    DEFF Research Database (Denmark)

    Gavito, A L; Cabello, R; Suarez, J

    2016-01-01

    BACKGROUND AND PURPOSE: Lipogenesis is intimately controlled by hormones and cytokines as well as nutritional conditions. IL-6 participates in the regulation of fatty acid metabolism in the liver. We investigated the role of IL-6 in mediating fasting/re-feeding changes in the expression of hepatic...... lipogenic enzymes. EXPERIMENTAL APPROACH: Gene and protein expression of lipogenic enzymes were examined in livers of wild-type (WT) and IL-6-deficient (IL-6(-/-) ) mice during fasting and re-feeding conditions. Effects of exogenous IL-6 administration on gene expression of these enzymes were evaluated...

  6. Coffee and Liver Disease.

    Science.gov (United States)

    Wadhawan, Manav; Anand, Anil C

    2016-03-01

    Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality.

  7. ROLE OF LEPTIN ON CYTOCHROME P-450 AND SOME LIVER MICROSOMAL ENZYMES ACTIVITIES IN THE OBESE AND LEAN MICE

    International Nuclear Information System (INIS)

    HEBEISHY, M.I.A.; MAZEN, G.M.A.; SHAHIN, M.I

    2008-01-01

    Leptin is a hormone that is secreted by adipocytes and regulates body weight through its effect on satiety and energy metabolism. The obese mouse is deficient in this protein and is characterized by obesity and other metabolic disorders. This study investigated the alterations of several hepatic cytochrome P 4 -5 0 (CYP), conjugation and antioxidant enzymes in lean and obese mice and the role of leptin in the modulation of these enzymes. Lean and obese male mice were injected with leptin (100 μg / rat) for 15 days. The obtained results revealed that administration of leptin to lean mice caused a significant elevation in the level of blood glucose, serum insulin, 6α, 6β, 16α- hydroxylation of testosterone, the activity of CYP 1 A 1 , CYP 4 A and GSH reductase in liver microsomes while serum corticosterone and the activity of total GSH were significantly decreased when compared to lean control mice. Moreover, obese mice treated with leptin recorded significant reduction in body weight, blood glucose concentration, serum levels of insulin and corticosterone, 7α and 16α- hydroxylation of testosterone, the activity of CYP 1A 1, CYP 2 B 1 and CYP 4 A and GST in liver microsomes. On the other hand, 6α, 6β-hydroxylation of testosterone, the activity of CYP 2 E 1 and GSH reductase in liver microsome were significantly increased when compared to obese control mice. The mechanism for the observed alterations may be due to direct leptin effects or via indirect alterations in insulin, corticosterone and/or growth hormone

  8. Effect of Simulated Microgravity on the Activity of Regulatory Enzymes of Glycolysis and Gluconeogenesis in Mice Liver

    Science.gov (United States)

    Ramirez, Joaquin; Periyakaruppan, Adaikkappan; Sarkar, Shubhashish; Ramesh, Govindarajan T.; Sharma, S. Chidananda

    2014-02-01

    Gravity supports all the life activities present on earth. Microgravity environments have effect on the biological functions and physiological status of an individual. The present study was undertaken to investigate the effect of simulated microgravity on important regulatory enzymes of carbohydrate metabolism in liver using HLS mice model. Following hind limb unloading of mice for 11 days the animal's average body weights were found to be not different, while the liver weights were decreased and found to be significantly different ( p gluconeogenesis in liver and reciprocally regulated.

  9. Evaluation of coagulation parameters and liver enzymes among alcohol drinkers in Port Harcourt, Nigeria

    Directory of Open Access Journals (Sweden)

    Adias TC

    2013-06-01

    Full Text Available Teddy Charles Adias,1 Everton Egerton,2 Osaro Erhabor3 1Bayelsa College of Health Technology, Bayelsa State, Nigeria; 2Department of Medical Laboratory Science, Rivers State University of Science and Technology, Port Harcourt, Nigeria; 3Faculty of Medical Laboratory Science, Department of Haematology and Transfusion Medicine, Usmanu Danfodiyo University, Sokoto, Nigeria Abstract: Alcohol is a major contributor to the global burden of disease, disability, and death in high, middle, and low-income countries. Harmful use of alcohol is one of the main factors contributing to premature deaths and avoidable disease burden worldwide and has a major impact on public health. The aim of this present cross-sectional study was to investigate the effect of alcohol consumption on coagulation parameters and liver enzymes of subjects in Port Harcourt, Nigeria. Two hundred adults consisting of 120 alcohol dependent subjects and 80 age, gender-matched nondrinkers aged 25–65 years (mean age 45.25 ± 11.50 years were enrolled in this study. Of the 120 chronic alcohol drinkers, 37 were dependent on local dry gin, while 83 were dependent on other alcoholic beverages. The mean values of the liver enzymes, aspartate aminotransferase and gamma glutamyl transferase, were significantly higher (P = 0.002 and P = 0.02 respectively among the chronic alcohol consumers compared with their nondrinker counterparts. Although the value of alanine aminotransferase was higher in the chronic drinkers, it did not reveal any significant difference (P = 0.11. The coagulation parameters, prothrombin time and activated partial thromboplastin time were investigated among chronic drinkers and nondrinkers. The mean value of prothrombin time and activated partial thromboplastin time was significantly higher in the chronic alcohol drinkers compared to the nondrinkers (P = 0.04 and P = 0.02 respectively. We observed a positive and significant correlation between values of liver enzymes, serum

  10. The mouse liver displays daily rhythms in the metabolism of phospholipids and in the activity of lipid synthesizing enzymes.

    Science.gov (United States)

    Gorné, Lucas D; Acosta-Rodríguez, Victoria A; Pasquaré, Susana J; Salvador, Gabriela A; Giusto, Norma M; Guido, Mario Eduardo

    2015-02-01

    The circadian system involves central and peripheral oscillators regulating temporally biochemical processes including lipid metabolism; their disruption leads to severe metabolic diseases (obesity, diabetes, etc). Here, we investigated the temporal regulation of glycerophospholipid (GPL) synthesis in mouse liver, a well-known peripheral oscillator. Mice were synchronized to a 12:12 h light-dark (LD) cycle and then released to constant darkness with food ad libitum. Livers collected at different times exhibited a daily rhythmicity in some individual GPL content with highest levels during the subjective day. The activity of GPL-synthesizing/remodeling enzymes: phosphatidate phosphohydrolase 1 (PAP-1/lipin) and lysophospholipid acyltransferases (LPLATs) also displayed significant variations, with higher levels during the subjective day and at dusk. We evaluated the temporal regulation of expression and activity of phosphatidylcholine (PC) synthesizing enzymes. PC is mainly synthesized through the Kennedy pathway with Choline Kinase (ChoK) as a key regulatory enzyme or through the phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway. The PC/PE content ratio exhibited a daily variation with lowest levels at night, while ChoKα and PEMT mRNA expression displayed maximal levels at nocturnal phases. Our results demonstrate that mouse liver GPL metabolism oscillates rhythmically with a precise temporal control in the expression and/or activity of specific enzymes.

  11. Metabolic Syndrome and Serum Liver Enzymes Level at Patients with Type 2 Diabetes Mellitus

    Science.gov (United States)

    Music, Miralem; Dervisevic, Amela; Pepic, Esad; Lepara, Orhan; Fajkic, Almir; Ascic-Buturovic, Belma; Tuna, Enes

    2015-01-01

    Objectives: The aim of this study was to evaluate liver function in patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MS) by determining serum levels of gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). We also investigated correlation between levels of liver enzymes and some components of MS in both groups of patients. Methods: This cross-sectional study included 96 patients (age 47–83 years) with T2DM. All patients were divided according to the criteria of the National Cholesterol Education Program (NCEP) in two groups: 50 patients with T2 DM and MS (T2DM-MS) and 46 patients with T2DM without MS (T2DM-Non MS). The analysis included blood pressure monitoring and laboratory tests: fasting blood glucose (FBG), total lipoprotein cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), fibrinogen and liver enzymes: GGT, ALT and AST. T2DM-MS group included patients which had FBG ≥ 6,1 mmol/L, TG ≥ 1,7 mmol/L and blood pressure ≥ 130/85 mm Hg. Results: T2DM-MS patients had significant higher values of systolic blood pressure, diastolic blood pressure and medium arterial pressure compared to T2DM-Non MS patients. Serum levels of TC, TG, LDL-C, VLDL-C and FBG were significantly higher in the T2DM-MS group compared to the T2DM-Non MS group. Serum fibrinogen level and GGT level were significantly higher in patients with T2DM-MS compared to the serum fibrinogen level and GGT level in T2DM-Non MS patients. Mean serum AST and ALT level were higher, but not significantly, in patients with T2DM and MS compared to the patients with T2DM without MS. Significant negative correlations were observed between TC and AST (r= -0,28, p<0,05), as well as between TC and ALT level (r= -0,29, p<0,05) in T2DM-MS group of patients. Conclusion: These results suggest that patients with T2DM and MS have markedly elevated liver enzymes. T2DM and MS probably play a role in

  12. Evaluation of the effects of hydroalcoholic extract of Berberis vulgaris root on the activity of liver enzymes in male hypercholesterolemic rats

    Directory of Open Access Journals (Sweden)

    Soheila Taheri

    2012-06-01

    Conclusion: Noticing the antioxidant properties of B. vulgaris root extract  and its effects on reducing the activity of liver enzymes, the extract of this plant can be a good choice for improving the function of liver.

  13. Preventive effect of zinc on nickel-induced oxidative liver injury in rats

    African Journals Online (AJOL)

    MIDOU

    2013-12-18

    Dec 18, 2013 ... induced oxidative liver injury and lipid peroxidation probably due to its antioxidant proprieties. ... enzyme in every enzyme classification (Coyle et al.,. 2002). Others .... control group had a regular histological structure with a.

  14. Serum activities of liver enzymes in workers exposed to sub-TLV levels of dimethylformamide

    Directory of Open Access Journals (Sweden)

    Jinjiang He

    2015-04-01

    Full Text Available Objectives: The aim of this study has been to investigate serum activities of liver enzymes in workers exposed to sub-TLV levels of dimethylformamide (DMF. Material and Methods: Seventy-two workers and 72 healthy controls participated in the study. All subjects underwent complete physical examinations and abdominal ultrasound examination. Serum aspartate aminotransferase (AST, alanine aminotransferase (ALT, and c-glutamyl transpeptidase (c-GT were determined by an auto-chemistry analyzer. The data of airborne concentrations of DMF was obtained from the local Center of Disease Control and Prevention. The level of urine N-acetyl-S-(N-methylcarbamoylcysteine (AMCC was measured by means of high-performance liquid chromatography. Results: Time weighted average (TWA concentration of the DMF in workplace was 18.6 (range: 9.8–36.2 mg/m3. The concentration of the AMCC in workers’ urine was 28.32 (range: 1.8–58.6 mg/l and 9 workers’ AMCC exceeded the biological exposure index (40 mg/l. Thirty-one workers reported gastrointestinal symptoms (abdominal pain, nausea, anorexia and 10 workers reported headache, dizziness and/or palpitation in the exposed group. Serum analysis revealed that both the mean of serum activities of liver enzymes (ALT, AST and c-GT and the percentage of workers with abnormal liver function were significantly higher in the exposed group as compared to the controls. Conclusions: Dimethylformamide can cause liver damage even if air concentration is in the sub-threshold limit value (sub-TLV level. The protection of skin contact against the exposure to the DMF might be a critical issue as far as the occupational health is concerned.

  15. Gene expression for peroxisome-associated enzymes in hepatocellular carcinomas induced by ciprofibrate, a hypolipidemic compound

    International Nuclear Information System (INIS)

    Rao, M.S.; Nemali, M.R.; Reddy, J.K.

    1986-01-01

    Administration of hypolipidemic compounds leads to marked proliferation of peroxisomes and peroxisome-associated enzymes (PAE) in the livers of rodents and non-rodent species. The increase peroxisome-associated enzymes such as fatty acid β-oxidation system and catalase is shown to be due to an increase in the levels of mRNA. In this experiment they have examined hepatocellular carcinomas (HCC), induced in male F-344 rats by ciprofibrate (0.025%, w/w for 60 weeks), for gene expression of PAE. Total RNA was purified from HCC as well as from control and ciprofibrate (0.025% for 2 weeks) fed rat livers. Northern blot analysis was performed using [32/sub p/]cDNA probes for albumin, fatty acetyl-CoA oxidase, enoyl-CoA hydratase 3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme and catalase. mRNA levels in HCC for albumin, fatty acid β-oxidation enzymes and catalase were comparable with those levels observed in the livers of rats given ciprofibrate for 2 weeks. In control livers the mRNAs for β-oxidation enzymes were low. Albumin mRNA levels in all the 3 groups were comparable. Additional studies are necessary to determine whether the increased level of mRNAs for the β-oxidation enzymes in HCC is due to the effect of ciprofibrate or to the gene amplification

  16. Serum levels of angiotensin converting enzyme as a biomarker of liver fibrosis

    Science.gov (United States)

    Miranda, Aline Silva; Simões e Silva, Ana Cristina

    2017-01-01

    The renin angiotensin system (RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues, including the liver, pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme (ACE)-angiotensin (Ang) II-Ang type 1 (AT1) receptor mediates pro-inflammatory, pro-thrombotic, and pro-fibrotic processes. On the other hand, the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang II action. Chronic hepatitis B (CHB) is one of the leading causes of liver fibrosis, accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However, the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36th issue of the World Journal of Gastroenterology, Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate, non-invasive, widely available, and easy method to evaluate fibrosis related to CHB. Moreover, therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis. PMID:29358853

  17. Carbamoyl-phosphate synthase (ammonia) of rat and axolotl liver: determination of immunological cross-reactivity without purification of the axolotl enzyme

    NARCIS (Netherlands)

    Lamers, W. H.; de Graaf, A.; Mooren, P. G.; Moorman, A. F.; Charles, R.

    1982-01-01

    A method has been developed to establish the degree of cross-reactivity of an antiserum raised against purified carbamoyl-phosphate synthase (ammonia) from adult rat liver, toward a homologous enzyme from another species without purification of the latter enzyme. For that purpose the ratio between

  18. Improved clinicopathologic assessments of acute liver damage due to trauma in Indian ring-necked parakeets (Psittacula krameri manillensis).

    Science.gov (United States)

    Williams, Susan M; Holthaus, Lisa; Barron, Heather Wilson; Divers, Stephen J; McBride, Michael; Almy, Frederic; Bush, Sharon; Latimer, Kenneth S

    2012-06-01

    Increased activities of certain biochemical enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], lactate dehydrogenase [LDH], alkaline phosphatase [ALP]) have been associated with blunt liver injury in many species. To evaluate changes in plasma hepatic biochemical parameters in acute avian liver disease caused by trauma and to compare biochemical changes with histologic lesions in hepatic parenchyma, 30 healthy fasted Indian ring-necked parakeets (Psittacula krameri manillensis) were divided into 2 groups, and traumatic liver injury was caused by endoscopic liver biopsy (group 1) or by liver biopsy and crushing injury to the hepatic parenchyma with endoscopic forceps (group 2) in anesthetized birds. Blood samples were collected at baseline and at 12, 24, 36, 48, 60, 72, 84, 96, 108, and 120 hours in alternate groups to compare analyte values after injury with those at baseline. Results showed consistently decreased plasma ALP activity (excluding 1 time point) throughout the study, which was thought to be associated with isoflurane administration. Plasma glutamate dehydrogenase activity initially increased but rapidly declined thereafter and was attributed to acute focal hepatocellular injury. In both groups, increases in plasma AST, ALT, and LDH activities was most likely caused by muscle injury because creatine kinase activity was concurrently increased. Compared with baseline values, bile acid concentration and y-glutamyl transferase activity were not affected by liver biopsy or crush injury. Plasma sorbitol dehydrogenase activity was the most specific indicator of liver injury in both groups. Histologic changes correlated poorly with biochemical results, possibly because the small area of hepatic parenchyma that was damaged did not affect enzyme values substantially.

  19. The Effect of Symbiotic Supplementation on Liver Enzymes, C-reactive Protein and Ultrasound Findings in Patients with Non-alcoholic Fatty Liver Disease: A Clinical Trial.

    Science.gov (United States)

    Asgharian, Atefe; Askari, Gholamreza; Esmailzade, Ahmad; Feizi, Awat; Mohammadi, Vida

    2016-01-01

    Regarding to the growing prevalence of nonalcoholic fatty liver disease (NAFLD), concentrating on various strategies to its prevention and management seems necessary. The aim of this study was to determine the effects of symbiotic on C-reactive protein (CRP), liver enzymes, and ultrasound findings in patients with NAFLD. Eighty NAFLD patients were enrolled in this randomized, double-blind, placebo-controlled clinical trial. Participants received symbiotic in form of a 500 mg capsule (containing seven species of probiotic bacteria and fructooligosaccharides) or a placebo capsule daily for 8 weeks. Ultrasound grading, CRP, and liver enzymes were evaluated at the baseline and the end of the study. In the symbiotic group, ultrasound grade decreased significantly compared to baseline (P symbiotic supplementation was not associated with changes in alanine aminotransferase (ALT) and aspartate transaminase (AST) levels. In the placebo group, there was no significant change in steatosis grade whereas ALT and AST levels were significantly increased (P = 0.002, P = 0.02, respectively). CRP values remained static in either group. Symbiotic supplementation improved steatosis in NAFLD patients and might be useful in the management of NAFLD or protective against its progression.

  20. Pharmacokinetic study of isocorynoxeine metabolites mediated by cytochrome P450 enzymes in rat and human liver microsomes.

    Science.gov (United States)

    Zhao, Lizhu; Zang, Bin; Qi, Wen; Chen, Fangfang; Wang, Haibo; Kano, Yoshihiro; Yuan, Dan

    2016-06-01

    Isocorynoxeine (ICN) is one of the major bioactive tetracyclic oxindole alkaloids found in Uncaria rhynchophylla (Miq.) Jacks. that is widely used for the treatment of hypertension, vascular dementia, and stroke. The present study was undertaken to assess the plasma pharmacokinetic characteristics of major ICN metabolites, and the role of simulated gastric and intestinal fluid (SGF and SIF), human and rat liver microsomes (HLMs and RLMs), and seven recombinant human CYP enzymes in the major metabolic pathway of ICN. A rapid, sensitive and accurate UHPLC/Q-TOF MS method was validated for the simultaneous determination of ICN and its seven metabolites in rat plasma after oral administration of ICN at 40mg/kg. It was found that 18.19-dehydrocorynoxinic acid (DCA) and 5-oxoisocorynoxeinic acid (5-O-ICA) were both key and predominant metabolites, rather than ICN itself, due to the rapid and extensive metabolism of ICN in vivo. The further study indicated that ICN was mainly metabolized in human or rat liver, and CYPs 2C19, 3A4 and 2D6 were the major enzymes responsible for the biotransformation of ICN to DCA and 5-O-ICA in human. These findings are of significance in understanding of the pharmacokinetic nature of tetracyclic oxindole alkaloids, and provide helpful information for the clinical co-administration of the herbal preparations containing U. rhynchophylla with antihypertensive drugs that are mainly metabolized by CYP3A4 and CYP2C19. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Drug-induced liver injury due to antibiotics.

    Science.gov (United States)

    Björnsson, Einar S

    Drug-induced liver injury (DILI) is an important differential diagnosis in patients with abnormal liver tests and normal hepatobiliary imaging. Of all known liver diseases, the diagnosis of DILI is probably one of the most difficult one to be established. In all major studies on DILI, antibiotics are the most common type of drugs that have been reported. The clinical phenotype of different types of antibiotics associated with liver injury is highly variable. Some widely used antibiotics such as amoxicillin-clavulanate have been shown to have a delayed onset on liver injury and recently cefazolin has been found to lead to liver injury 1-3 weeks after exposure of a single infusion. The other extreme is the nature of nitrofurantoin-induced liver injury, which can occur after a few years of treatment and lead to acute liver failure (ALF) or autoimmune-like reaction. Most patients with liver injury associated with use of antibiotics have a favorable prognosis. However, patients with jaundice have approximately 10% risk of death from liver failure and/or require liver transplantation. In rare instances, the hepatoxicity can lead to chronic injury and vanishing bile duct syndrome. Given, sometimes very severe consequences of the adverse liver reactions, it cannot be over emphasized that the indication for the different antibiotics should be evidence-based and symptoms and signs of liver injury from the drugs should lead to prompt cessation of therapy.

  2. L-malate enhances the gene expression of carried proteins and antioxidant enzymes in liver of aged rats.

    Science.gov (United States)

    Zeng, X; Wu, J; Wu, Q; Zhang, J

    2015-01-01

    Previous studies in our laboratory reported L-malate as a free radical scavenger in aged rats. To investigate the antioxidant mechanism of L-malate in the mitochondria, we analyzed the change in gene expression of two malate-aspartate shuttle (MAS)-related carried proteins (AGC, aspartate/glutamate carrier and OMC, oxoglutarate/malate carrier) in the inner mitochondrial membrane, and three antioxidant enzymes (CAT, SOD, and GSH-Px) in the mitochondria. The changes in gene expression of these proteins and enzymes were examined by real-time RT-PCR in the heart and liver of aged rats treated with L-malate. L-malate was orally administered in rats continuously for 30 days using a feeding atraumatic needle. We found that the gene expression of OMC and GSH-Px mRNA in the liver increased by 39 % and 38 %, respectively, in the 0.630 g/kg L-malate treatment group than that in the control group. The expression levels of SOD mRNA in the liver increased by 39 %, 56 %, and 78 % in the 0.105, 0.210, and 0.630 g/kg L-malate treatment groups, respectively. No difference were observed in the expression levels of AGC, OMC, CAT, SOD, and GSH-Px mRNAs in the heart of rats between the L-malate treatment and control groups. These results predicted that L-malate may increase the antioxidant capacity of mitochondria by enhancing the expression of mRNAs involved in the MAS and the antioxidant enzymes.

  3. Comparative liver accumulation of dioxin-like compounds in sheep and cattle: Possible role of AhR-mediated xenobiotic metabolizing enzymes.

    Science.gov (United States)

    Girolami, F; Spalenza, V; Benedetto, A; Manzini, L; Badino, P; Abete, M C; Nebbia, C

    2016-11-15

    PCDDs, PCDFs, and PCBs are persistent organic pollutants (POPs) that accumulate in animal products and may pose serious health problems. Those able to bind the aryl hydrocarbon receptor (AhR), eliciting a plethora of toxic responses, are defined dioxin-like (DL) compounds, while the remainders are called non-DL (NDL). An EFSA opinion has highlighted the tendency of ovine liver to specifically accumulate DL-compounds to a greater extent than any other farmed ruminant species. To examine the possible role in such an accumulation of xenobiotic metabolizing enzymes (XME) involved in DL-compound biotransformation, liver samples were collected from ewes and cows reared in an area known for low dioxin contamination. A related paper reported that sheep livers had about 5-fold higher DL-compound concentrations than cattle livers, while the content of the six marker NDL-PCBs did not differ between species. Specimens from the same animals were subjected to gene expression analysis for AhR, AhR nuclear translocator (ARNT) and AhR-dependent oxidative and conjugative pathways; XME protein expression and activities were also investigated. Both AhR and ARNT mRNA levels were about 2-fold lower in ovine samples and the same occurred for CYP1A1 and CYP1A2, being approximately 3- and 9-fold less expressed in sheep compared to cattle, while CYP1B1 could be detectable in cattle only. The results of the immunoblotting and catalytic activity (most notably EROD) measurements of the CYP1A family enzymes were in line with the gene expression data. By contrast, phase II enzyme expression and activities in sheep were higher (UGT1A) or similar (GSTA1, NQO1) to those recorded in cattle. The overall low expression of CYP1 family enzymes in the sheep is in line with the observed liver accumulation of DL-compounds and is expected to affect the kinetics and the dynamics of other POPs such as many polycyclic aromatic hydrocarbons, as well as of toxins (e.g. aflatoxins) or drugs (e.g. benzimidazole

  4. Protective Effect of Prosopis cineraria Against N-Nitrosodiethylamine Induced Liver Tumor by Modulating Membrane Bound Enzymes and Glycoproteins

    Directory of Open Access Journals (Sweden)

    Naina Mohamed Pakkir Maideen

    2012-06-01

    Full Text Available Purpose: The objective of the present study was to evaluate the protective effect of methanol extract of Prosopis cineraria (MPC against N-nitrosodiethylamine (DEN, 200mg/kg induced Phenobarbital promoted experimental liver tumors in male Wistar rats. Methods: The rats were divided into four groups, each group consisting of six animals. Group 1 served as control animals. Liver tumor was induced in group 2, 3, and 4 and Group 3 animals received MPC 200mg/kg and Group 4 animals received MPC 400mg/kg. Results: Administration of DEN has brought down the levels of membrane bound enzymes like Na+/ K+ ATPase, Mg2+ ATPase and Ca2+ATPase which were later found to be increased by the administration of Prosopis cineraria (200 and 400mg/kg in dose dependent manner. The MPC extract also suppressed the levels of glycoproteins like Hexose, Hexosamine and Sialic acid when compared to liver tumor bearing animals. Conclusions: Our study suggests that MPC may extend its protective role by modulating the levels of membrane bound enzymes and suppressing glycoprotein levels.

  5. Thrombospondin-1 expression may be implicated in liver atrophic mechanism due to obstructed portal venous flow.

    Science.gov (United States)

    Hayashi, Hiromitsu; Kuroki, Hideyuki; Higashi, Takaaki; Takeyama, Hideaki; Yokoyama, Naomi; Okabe, Hirohisa; Nitta, Hidetoshi; Beppu, Toru; Takamori, Hiroshi; Baba, Hideo

    2017-07-01

    Liver is an amazing organ that can undergo regenerative and atrophic changes inversely, depending on blood flow conditions. Although the regenerative mechanism has been extensively studied, the atrophic mechanism remains to be elucidated. To assess the molecular mechanism of liver atrophy due to reduced portal blood flow, we analyzed the gene expressions between atrophic and hypertrophic livers induced by portal vein embolization in three human liver tissues using microarray analyses. Thrombospondin (TSP)-1 is an extracellular protein and a negative regulator of liver regeneration through its activation of the transforming growth factor-β/Smad signaling pathway. TSP-1 was extracted as the most upregulated gene in atrophic liver compared to hypertrophic liver due to portal flow obstruction in human. Liver atrophic and hypertrophic changes were confirmed by HE and proliferating cell nuclear antigen staining and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling. In an in vivo model with portal ligation, TSP-1 and phosphorylated Smad2 expression were continuously induced at 6 h and thereafter in the portal ligated liver, whereas the induction was transient at 6 h in the portal non-ligated liver. Indeed, while cell proliferation represented by proliferating cell nuclear antigen expression at 48 h was induced in the portal ligated liver, the sinusoidal dilatation and hepatocyte cell death with terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling was detectable at 48 h in the portal ligated liver. Obstructed portal flow induces persistent TSP-1 expression and transforming growth factor-β/Smad signal activation in atrophic liver. Thrombospondin-1 may be implicated in the liver atrophic change due to obstructed portal flow as a pro-atrophic factor. © 2016 The Japan Society of Hepatology.

  6. Evaluation of liver enzyme levels in workers exposed to vinyl chloride vapors in a petrochemical complex: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Dolati Mandana

    2007-08-01

    Full Text Available Abstract Background Polyvinyl chloride is used in production and manufacturing of many essential tools (e.g. plastic pipes, photography films, etc.. Its production is impossible without the use of vinyl chloride monomer (VCM, which can cause liver damage in long-term. In this study we intend to assess the effects of mild to moderate long term exposure to VCM on liver and to assess the importance of liver enzyme measurements as a screening tool. Methods In this study, liver enzyme levels of 52 workers were compared to 48 control workers using the T-test. The cases all worked in a PVC production unit in a petrochemical complex and the controls were randomly selected from office personnel of the same complex. A questionnaire was also filled in about information such as age, weight, work history, etc. in both groups. Results Mean comparisons for ALP and GGT using T-test showed statistically significant differences between the two groups. For AST, ALT and bilirubin (total, direct the mean was higher in the case group but this difference was not statistically significant. Discussion This study showed that mild exposure to VCM can cause mild liver cholestasis. So, using cholestasis assessment tests such as ALP and GGT should be considered in periodic assessment of liver function in PVC producing units.

  7. Effects of coenzyme Q10 supplementation on the anthropometric variables, lipid profiles and liver enzymes in patients with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Elnaz Jafarvand

    2016-03-01

    Full Text Available This randomized double-blind placebo-controlled trial was conducted on 41 patients with non-alcoholic fatty liver disease. Patients in intervention group received 100 mg/day coenzyme Q10 (CoQ10 for four weeks. There was a significant reduction in waist circumference and aspartate aminotransferase concentrations after CoQ10 supplementation (p<0.05. Dietary fiber was in negative correlation with change in serum alanine aminotransferase (ALT concentrations (r = -410, p = 0.04, and dietary fat intake was in positive relation with serum triglyceride (r = 463, p = 0.04 and in negative relation with serum high-density lipoprotein cholesterol (HDL-C (r = -533, p = 0.02 in CoQ10-treated group. CoQ10 supplement is able to reduce central obesity and improve liver function in non-alcoholic fatty liver disease. Dietary factors were also significant determinants of change in liver-specific enzyme ALT and lipid profile in these patients. Further trials with higher dose of CoQ10 and longer treatment periods are warranted to better clarify these findings.

  8. Pre-existing liver cirrhosis reduced the toxic effect of diethylene glycol in a rat model due to the impaired hepatic alcohol dehydrogenase.

    Science.gov (United States)

    Ming Xing Huang; Xiao Mou Peng; Lin Gu; Gui Hua Chen

    2011-09-01

    Hepatic metabolizing enzymes of diethylene glycol (DEG) are impaired in liver diseases. Thus, the purpose of this study was to increase our understandings in metabolism and toxicology of DEG by clarifying the influences of pre-existing liver disease. Forty Sprague-Dawley rats with carbon tetrachloride-induced liver cirrhosis and 20 control rats were intraperitoneally administered a single dose of DEG, and randomly killed 1, 2, 5 or 8 days following exposure. Compared with control rats, the model rats had significantly higher blood CO(2)-combining power, lower blood urine nitrogen, serum creatinine and alanine aminotransferase levels on the second day and a lower mortality rate on the eighth day following DEG exposure. Enlargements of liver and kidneys and degeneration and necrosis of hepatocytes and renal tubules in the model rats was also less serious than in the control rats. Urine DEG levels were significantly higher on the first day in the model rats than the control rats (46.65 ± 8.79 mg vs 18.88 ± 6.18 mg, p activity in the model rats was significantly lower than that in the control rats, which was positively related to renal damage. The toxic effects of DEG in rats with pre-existing liver cirrhosis are significantly reduced, which may be due to the decreased hepatic ADH activity. It suggests that the metabolite of ADH is responsible for DEG poisoning, and this toxic metabolite may mainly originate in the liver.

  9. Vitamin B2 content determination in liver paste by using acid and acid-enzyme hydrolysis

    Directory of Open Access Journals (Sweden)

    Basić Zorica

    2007-01-01

    the samples (r = 0.9994, and r = 0.99987. Hydrolysis procedures make a sample suitable for vitamin B2 determination. In the liver paste samples a high content of vitamin B2 was determined: 0.83 mg/100 g after acid hydrolysis, and 0.909 mg/100 g after acid-enzyme hydrolysis. There were statistically significantly higher values determined after the acid-enzyme hydrolysis (p < 0.05. Conclusion. Using acid-enzyme hydrolysis and separation instrument technique (liquid chromatography with a fluorescent detector as detection system, statistically significantly greater vitamin B2 quantities were determined than after using acid hydrolysis procedure. Vitamin B2 content determined in ten liver paste samples was high (0.881 − 0.936 mg/100g indicating that this meat product is a good vitamin B2 source.

  10. Effects of Cinnamon extract on biochemical enzymes, TNF-α and NF-κB gene expression levels in liver of broiler chickens inoculated with Escherichia coli

    Directory of Open Access Journals (Sweden)

    Seyed Mahmoud Tabatabaei

    2015-09-01

    Full Text Available Abstract: Infection with Escherichia coli (E. coli is a common disease in poultry industry. The use of antibiotics to treat diseases is facing serious criticism and concerns. The medicinal plants may be effective alternatives because of their multiplex activities. The aim of this study was to investigate the effects of cinnamon extract on the levels of liver enzymes, tumor necrosis factor-alpha (TNF-α and nuclear factor-kappa B (NF-κB gene expressions in liver of broiler chickens infected with E. coli. Ninety Ross-308 broilers were divided into healthy or E. coli-infected groups, receiving normal or cinnamon extract (in concentrations of 100 or 200mg/kg of food supplemented diets. E. coli suspension (108cfu was injected subcutaneously after 12 days cinnamon administration. Seventy-two hours after E. coli injection, the blood samples were taken for biochemical analysis of liver enzymes in serum (spectrophotometrically, and liver tissue samples were obtained for detection of gene expression of inflammatory markers TNF-α and NF-κB, using real-time PCR. Infection with E. coli significantly increased the levels of TNF-α and NF-κB gene expressions as well as some liver enzymes including creatine-kinase (CK, lactate-dehydrogenase (LDH, alanine-transferase (ALT and aspartate-transferase (AST as compared with control group (P<0.05. Pre-administration of cinnamon extract in broilers diet (in both concentrations significantly reduced the tissue levels of TNF-α and NF-κB gene expressions and enzymes CK and ALT in serum of broiler chickens inoculated with E. coli in comparison with E. coli group (P<0.05 and P<0.01. The levels of LDH and AST were significantly decreased only by 200mg/kg cinnamon extract in infected broilers. The level of alkaline-phosphatase (ALP was not affected in any groups. Pre-administration of cinnamon extract in diets of broiler chickens inoculated with E. coli could significantly reduce the gene expression levels of pro

  11. Computer tomographic findings in portal hypertension due to cirrhosis of the liver. Pt. 3

    International Nuclear Information System (INIS)

    Koester, O.; Fischer, P.; Lindecken, K.D.; Lackner, K.; Bonn Univ.

    1984-01-01

    Contract injection for angio-CT shows kinetic changes in patients with portal hypertension due to cirrhosis of the liver when compared with normals. Contrast-duration diagrams show a higher aortic peak, low contrast and delayed contrast maximum in the liver and protal vein in patients with liver cirrhosis and portal hypertension. On these criteria it is possible to distinguish patients with cirrhosis (n = 18) from normals (n = 16). (orig.) [de

  12. Computer tomographic findings in portal hypertension due to cirrhosis of the liver. Pt. 3

    Energy Technology Data Exchange (ETDEWEB)

    Koester, O; Fischer, P; Lindecken, K D; Lackner, K

    1984-03-01

    Contract injection for angio-CT shows kinetic changes in patients with portal hypertension due to cirrhosis of the liver when compared with normals. Contrast-duration diagrams show a higher aortic peak, low contrast and delayed contrast maximum in the liver and protal vein in patients with liver cirrhosis and portal hypertension. On these criteria it is possible to distinguish patients with cirrhosis (n = 18) from normals (n = 16). 5 figs.

  13. First Trimester Hemolysis, Elevated Liver Enzymes, Low Platelets Syndrome in a Surrogate Pregnancy

    OpenAIRE

    Myer, Emily; Hill, James

    2015-01-01

    Background The occurrence of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 20 weeks of gestation is rare. HELLP is a possible but rare syndrome in gestational surrogate pregnancies for surrogates with risk factors for development of preeclampsia. Case A 32-year-old patient with chronic hypertension and positive antinuclear antibody presented for prenatal care at 13 weeks and 1 day. She was a surrogate for the embryo of a 43-year-old couple. By 15 weeks she developed...

  14. Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

    International Nuclear Information System (INIS)

    Chen, Qi-Liang; Luo, Zhi; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

    2013-01-01

    Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

  15. Differential induction of enzymes and genes involved in lipid metabolism in liver and visceral adipose tissue of juvenile yellow catfish Pelteobagrus fulvidraco exposed to copper

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qi-Liang; Luo, Zhi, E-mail: luozhi99@yahoo.com.cn; Pan, Ya-Xiong; Zheng, Jia-Lang; Zhu, Qing-Ling; Sun, Lin-Dan; Zhuo, Mei-Qin; Hu, Wei

    2013-07-15

    Highlights: •Cu downregulates lipogenesis and reduces lipid deposition in liver and adipose tissue. •Mechanism of Cu affecting lipid metabolism is determined at the enzymatic and molecular levels. •Cu exposure differentially influences lipid metabolism between liver and adipose tissue. -- Abstract: The present study was conducted to determine the mechanism of waterborne Cu exposure influencing lipid metabolism in liver and visceral adipose tissue (VAT) of juvenile yellow catfish Pelteobagrus fulvidraco. Yellow catfish were exposed to four waterborne copper (Cu) concentrations (2 (control), 24 (low), 71 (medium), 198 (high) μg Cu/l, respectively) for 6 weeks. Waterborne Cu exposure had a negative effect on growth and several condition indices (condition factor, viscerosomatic index, hepatosomatic index and visceral adipose index). In liver, lipid content, activities of lipogenic enzymes (6-phosphogluconate dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), malic enzyme (ME), isocitrate dehydrogenase (ICDH), and fatty acid synthase (FAS)) as well as mRNA levels of 6PGD, G6PD, FAS and sterol-regulator element-binding protein-1 (SREBP-1) genes decreased with increasing Cu concentrations. However, activity and mRNA level of lipoprotein lipase (LPL) gene in liver increased. In VAT, G6PD, ME and LPL activities as well as the mRNA levels of FAS, LPL and PPARγ genes decreased in fish exposed to higher Cu concentrations. The differential Pearson correlations between transcription factors (SREBP-1 and peroxisome proliferators-activated receptor-γ (PPARγ)), and the activities and mRNA expression of lipogenic enzymes and their genes were observed between liver and VAT. Thus, our study indicated that reduced lipid contents in liver and VAT after Cu exposure were attributable to the reduced activities and mRNA expression of lipogenic enzymes and their genes in these tissues. Different response patterns of several tested enzymes and genes to waterborne Cu

  16. Effects of Angiotensin Converting Enzyme Inhibitors on Liver Fibrosis in HIV and Hepatitis C Coinfection

    Directory of Open Access Journals (Sweden)

    Lindsey J. Reese

    2012-01-01

    Full Text Available Background. Liver fibrosis is accelerated in HIV and hepatitis C coinfection, mediated by profibrotic effects of angiotensin. The objective of this study was to determine if angiotensin converting enzyme inhibitors (ACE-Is attenuate liver fibrosis in coinfection. Methods. A retrospective review of 156 coinfected subjects was conducted to analyze the association between exposure to ACE-Is and liver fibrosis. Noninvasive indices of liver fibrosis (APRI, FIB-4, Forns indices were compared between subjects who had taken ACE-Is and controls who had not taken them. Linear regression was used to evaluate ACE-I use as an independent predictor of fibrosis. Results. Subjects taking ACE-Is for three years were no different than controls on the APRI and the FIB-4 but had significantly higher scores than controls on the Forns index, indicating more advanced fibrosis. The use of ACE-Is for three years remained independently associated with an elevated Forns score when adjusted for age, race, and HIV viral load (P<0.001. There were significant associations between all of the indices and significant fibrosis, as determined clinically and radiologically. Conclusions. There was not a protective association between angiotensin inhibition and liver fibrosis in coinfection. These noninvasive indices may be useful for ruling out significant fibrosis in coinfection.

  17. Promoting effects of phenobarbital on the enzyme-altered foci induced by intrahepatic γ-ray-irradiation in the rat liver

    International Nuclear Information System (INIS)

    Ida, Katsuya; Nakamura, Satoshi; Muro, Hiroyuki; Takai, Michikatsu; Kaneko, Masao

    1995-01-01

    Radiation-induced carcinogenesis of the rat liver using iridium-192 seeds as an intrahepatic radioactive source was studied by enzyme histochemical means. Rats were divided into six groups according to various combinations of one or two iridium-192 or stainless steel seeds and whether they were given a diet containing 0.05% phenobarbital (PB) or a basal diet (BD). Each group were sacrificed at 20, 40, and 60 weeks after intrahepatic insertion of the iridium-192 or stainless steel seeds. γ-Glutamyl transpeptidase (GGT), glucose-6-phosphatase (G6Pase), and adenosine triphosphatase (ATPase) were stained in the liver tissues, and GGT-positive foci were quantified. Liver neoplasm was not evident, but enzyme-altered foci (EAF) were induced by γ-ray irradiation. At every point (20, 40, and 60 weeks) after the insertion of the seeds, the GGT-positive area was larger in the rats given PB than those given BD. Moreover, despite the iridium-192 radioactivity decay, EAF developed continuously in the rats given PB, and persisted in those given BD from 40 to 60 weeks after insertion. These results indicated that phenobarbital promotes the development of EAF initiated by irradiation, as it promotes the process of chemical carcinogenesis in the rat liver. (author)

  18. Concomitant apoptosis and regeneration of liver cells as a mechanism of liver-tumor promotion by β-naphthoflavone involving TNFα-signaling due to oxidative cellular stress in rats

    International Nuclear Information System (INIS)

    Kuwata, Kazunori; Shibutani, Makoto; Hayashi, Hitomi; Shimamoto, Keisuke; Hayashi, Shim-Mo; Suzuki, Kazuhiko; Mitsumori, Kunitoshi

    2011-01-01

    β-Naphthoflavone (BNF) is a strong inducer of cytochrome P450 1A enzymes, and exerts liver tumor-promoting activity through enhancement of oxidative stress responses in rats. This study investigated the role of the tissue environment surrounding hepatocellular preneoplastic lesions in the early tumor-promotion stage by BNF, using enzymatically modified isoquercitrin (EMIQ) as an anti-oxidative chemopreventive agent. Male F344 rats were fed a diet containing BNF (0.5%) for 6 weeks, with or without EMIQ (0.2%) in the drinking water, 2 weeks after initiation with N-diethylnitrosamine, and were subjected to two-thirds partial hepatectomy 1 week after starting BNF-promotion. BNF-treatment increased concentrations of liver thiobarbituric acid-reactive substances, single liver cells expressing glutathione S-transferase placental form or heme oxygenase (HO)-1, and concomitant apoptosis and proliferation of liver cells. Transcript upregulation of anti-oxidative enzymes (Aldh1a1 and Nqo1), cell cycle-related molecules (Cdc20 and Cdkn2b) and inflammation-related molecules including proinflammatory cytokines (Ccl2, Col1a1, Il6, Nos2 and Serpine1) was also evident. Furthermore, BNF increased HO-1-expressing Kupffer cells and liver cells expressing tumor necrosis factor receptor 1 (TNFR1) and the TNFR1-associated death domain. Most of these BNF-induced fluctuations disappeared or were suppressed by EMIQ in conjunction with suppression of tumor-promotion. Tnf transcript levels with BNF were also suppressed by EMIQ. These results suggest that BNF-induced oxidative stress causes single liver cell toxicity, allowing subsequent concomitant apoptosis and regeneration involving inflammatory responses including TNFα-signaling, contributing to tumor promotion. Kupffer cells may act to protect against inflammatory stimuli induced as a result of oxidative cellular stress by BNF, causing proinflammatory cytokine level fluctuations.

  19. Association between hepatic steatosis and serum liver enzyme levels with atrial fibrillation in the general population: The Study of Health in Pomerania (SHIP).

    Science.gov (United States)

    Markus, Marcello Ricardo Paulista; Meffert, Peter J; Baumeister, Sebastian Edgar; Lieb, Wolfgang; Siewert, Ulrike; Schipf, Sabine; Koch, Manja; Kors, Jan A; Felix, Stephan Burkhard; Dörr, Marcus; Targher, Giovanni; Völzke, Henry

    2016-02-01

    Hepatic steatosis (HS) affects up to 35% of adults in the general population. Atrial fibrillation (AF) is the most prevalent sustained arrhythmia and has a substantial impact on healthcare costs. We analyzed cross-sectional associations of HS and serum liver enzyme levels with prevalent AF in a general population sample. We analyzed data from 3090 women and men, aged 20-81 years, from the population-based Study of Health in Pomerania. HS was determined by ultrasonography. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltranspeptidase (GGT) were measured photometrically. AF was determined by automatic electrocardiographic analysis software. The prevalences of HS and AF were 30.3% and 1.49%, respectively. ALT, AST and GGT showed a positive linear association with the risk of prevalent AF, after multivariable adjustment. The adjusted odds ratios for AF per 1-standard deviation increment in log-transformed serum liver enzyme levels were 1.65 (95% confidence interval [CI]: 1.16 to 2.35; p = 0.006) for ALT, 1.47 (95%CI: 1.07 to 2.02; p = 0.017) for AST and 2.17 (95%CI: 1.64 to 2.87; p < 0.001) for GGT. In contrast, ultrasonographic HS was not associated with AF. Our findings indicate that moderately elevated serum liver enzymes, but not sonographic liver hyperechogenicity, were associated with increased AF prevalence in the general adult population. The hepatic release of increased levels of serum liver enzymes might be accompanied by higher levels of pro-inflammatory, pro-coagulant and pro-fibronogenic mediators that might lead to structural and electrical remodeling of the atrium resulting in the development and persistence of AF. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. The relationship between 25-hydroxyvitamin D concentration and liver enzymes in overweight or obese adults: Cross-sectional and interventional outcomes.

    Science.gov (United States)

    Naderpoor, Negar; Mousa, Aya; de Courten, Maximilian; Scragg, Robert; de Courten, Barbora

    2018-03-01

    Vitamin D deficiency is prevalent in individuals with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis. However, there is limited and inconsistent data on the effect of vitamin D supplementation on liver function. Hepatic enzymes have been used as surrogate markers for NAFLD and have been associated with metabolic syndrome. We examined the relationships between 25-hydroxyvitamin D (25(OH)D) and γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), alkaline phosphatase (ALP) in 120 drug-naïve individuals with no history of liver disease. In addition, the effect of vitamin D supplementation (100,000 loading dose of cholecalciferol followed by 4000IU daily for 16 weeks) on hepatic enzymes was investigated in a subgroup of 54 vitamin D-deficient overweight or obese individuals (28 randomised to cholecalciferol and 26 to placebo). Hepatic enzymes, anthropometric parameters, lipid profile, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp, M value) and high sensitivity C-reactive protein (hs-CRP) were measured before and after the intervention. In the cross-sectional study, levels of GGT and ALT were higher in men compared to women (both p=0.001). There were no significant differences in GGT, ALT and ALP between vitamin D categories (25(OH)D50nmol/L) and no relationships were found between the three enzymes and 25(OH)D before and after adjustment for age, sex, BMI, WHR, and insulin sensitivity (all p>0.5). In the randomised trial, 25(OH)D concentrations increased in the vitamin D group (mean change 57.0±21.3nmol/L) compared to the placebo group (mean change 1.9±15.1nmol/L). Mean changes in GGT, ALT and ALP were not significantly different between vitamin D and placebo groups (all p>0.2). Change in 25(OH)D concentration was not correlated with changes in GGT, ALT and ALP before and after adjustments for age and sex (all p>0.1). In summary, 25(OH)D concentrations were not related to hepatic enzymes in drug-naive adults with no

  1. In vitro modulatory effects of Terminalia arjuna, arjunic acid, arjunetin and arjungenin on CYP3A4, CYP2D6 and CYP2C9 enzyme activity in human liver microsomes

    Directory of Open Access Journals (Sweden)

    Alice Varghese

    2015-01-01

    Full Text Available Terminalia arjuna is a tree having an extensive medicinal potential in cardiovascular disorders. Triterpenoids are mainly responsible for cardiovascular properties. Alcoholic and aqueous bark extracts of T. arjuna, arjunic acid, arjunetin and arjungenin were evaluated for their potential to inhibit CYP3A4, CYP2D6 and CYP2C9 enzymes in human liver microsomes. We have demonstrated that alcoholic and aqueous bark extract of T. arjuna showed potent inhibition of all three enzymes in human liver microsomes with IC50 values less than 50 μg/mL. Arjunic acid, arjunetin and arjungenin did not show significant inhibition of CYP enzymes in human liver microsomes. Enzyme kinetics studies suggested that the extracts of arjuna showed reversible non-competitive inhibition of all the three enzymes in human liver microsomes. Our findings suggest strongly that arjuna extracts significantly inhibit the activity of CYP3A4, CYP2D6 and CYP2C9 enzymes, which is likely to cause clinically significant drug–drug interactions mediated via inhibition of the major CYP isozymes.

  2. The Effect of Myrtus communis Extract on Liver Enzymes and Blood Biochemical Factors in Diabetic Adult Male Rats

    Directory of Open Access Journals (Sweden)

    Habiballah Johari

    2014-10-01

    Full Text Available Background: The aim of this study was the effect of Myrtus communis extract on liver enzymes and blood biochemical factors in diabetic adult male rats. Materials and Methods: This study has been carried out experimentally and completely random. Seventy adult male Wistar rats were divided in 7 groups including: control which received no treatment, sham who received 2 mL of distilled water, the 1st, 2nd and 3rd experimental groups which received 0.75, 1.5 and 3 mg/kg Myrtus communis leaf extract respectively, the 4th experimental group as the diabetic control group who received streptozotocin (60 mg/kg and the 5th experimental group as the diabetic treatment group who received 3 mg/kg of extract. This experiment lasted 14 days with prescript orally. After this period, all the rats, were weighted, anesthetized and blood samples were taken from the heart centrifuged and sera were evaluated for the concentration of various factors. In addition liver were removed and sliced. Results: According to the obtained results, the plasma concentration of liver enzyme (alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, cholesterol and glucose presented a significant decrease at (p≤0.05. Whereas no significant change were seen in body weight, triglyceride, urea, albumin and total protein. Histological studies of the liver tissue showed no significant difference among various groups. Conclusion: Myrtus communis is comprise of collections of flavonoids and other various components with antioxidant and anti inflammatory properties. Thence it can effective in treatment of liver diseases and decrease of blood sugar and cholesterol in diabetes mellitus patients.

  3. Dynamics of some conjugated enzymes of aminonitrogen metabolism in the liver of the irradiated body

    International Nuclear Information System (INIS)

    Savitskij, V.I.

    1976-01-01

    Changes in the activity of five conjugated enzymes of the aminonitrogen metabolism in subcellular fractions of liver tissue have been studied on irradiated (450 R) rabbits during thirty days after exposure. These changes are peculiar for their manifestation in time, their depth and trend. It is suggested that in the early period of radiation damage, gluconeogenesis is enhanced, and in the later period, biosynthesis of pyrimidine bases is intensified

  4. The Role of Liver Biopsy in the Management of Patients with Liver Disease

    Directory of Open Access Journals (Sweden)

    Florence Wong

    2003-01-01

    Full Text Available The role of liver biopsy in the diagnosis and management of liver disease is a controversial issue even among hepatologists. Although most causes of elevated liver enzymes can be determined, or at least suspected, on the basis of a careful history and laboratory tests, histological assessment remains the gold standard for most liver diseases. Histological evaluation can either confirm or refute clinical diagnoses and can provide information about the severity and stage of disease. Occasionally, the liver biopsy also provides an additional diagnosis. The spectrum of nonalcoholic fatty liver disease accounts for a substantial proportion of cases of chronically elevated liver enzymes and can be reliably diagnosed only by liver biopsy. Prognostic information can be obtained in patients with this disorder, as well as in those with alcoholic liver disease and viral hepatitis, and liver biopsy can be used as a guide to their management.

  5. Pyogenic liver abscess and peritonitis due to Rhizopus oryzae in a child with Papillon-Lefevre syndrome.

    Science.gov (United States)

    Dalgic, Buket; Bukulmez, Aysegul; Sari, Sinan

    2011-06-01

    Papillon-Lefevre syndrome (PLS) is an autosomal recessive disease that is characterized by symmetric palmoplantar keratodermatitis and severe periodontal destruction. Mutations in the cathepsin C gene (CTSC) have recently been detected in PLS. Immune dysregulation, due to a mutation in CTSC, increases the risk of pyogenic infections in PLS patients. A child with PLS is presented here with liver abscesses and peritonitis caused by Rhizopus oryzae. His liver abscess and peritonitis were cured with amphotericin B without surgical care. This is the first case in the literature liver abscess due to Rhizopus oryzae in a child with PLS.

  6. Changes of α-glycerophosphate dehydrogenase activity in fatty liver of rats by amino acid imbalance

    International Nuclear Information System (INIS)

    Ogura, Masaji; Katsunuma, Eiichi; Akabane, Tomoko; Ogawa, Seiichi

    1976-01-01

    The previous study on the lipogenesis in the fatty livers of rats, which was induced by feeding the diet with imbalanced amino acid, revealed that the induction of this type of fatty livers was due mainly to the acceleration of triglyceride synthesis by the increase in both synthesis and esterification of fatty acid in the livers. Although many studies have been carried out on the dietary control of α-glycerophosphate dehydrogenase activity in rat livers, the enzyme change in amino acid imbalance has not been reported. In the present study, in order to elucidate the difference in the supply of glycerol moiety of triglyceride due to the imbalance, the change of the α-glycerophosphate dehydrogenase activity in livers was investigated. The experimental diets were 8% casein basal diet and basal + 0.3% DL-methionine imbalanced diet. 5 rats of each group were killed after 0.5 and 10 days on the diet, and the analysis of the lipid content in the livers and the determination of the α-glycerophosphate dehydrogenase activity were carried out. The linear response of the enzyme activity to time and protein concentration was obtained. The development of fatty livers was observed in the imbalanced diet group in the feeding period of 10 days. It was found that the specific activity of the imbalanced diet group increased significantly in 5 and 10 days as compared with that of the basal diet group. The elevation in the enzyme activity may suggest that the supply of α-glycerophosphate for triglyceride synthesis is also increased in this type of fatty livers. (Kako, I.)

  7. ENZYME MARKERS ACTIVITY AND BILE FORMATION FUNCTION OF LIVER IN CASES OF TUBERCULOSTATICS AND HEXAVALENT CHROMIUM COMPOUNDS AFFECTION IN RATS

    OpenAIRE

    N. I. Burmas; L. S. Fira; P. H. Lyhackyy

    2016-01-01

    Background. Currently, the growing incidence of toxic lesions of the liver is associated with industrial chemicalization and uncontrolled use of hepatotoxic drugs in everyday life. There are about one thousand drugs with high or low hepatotoxicity, such as anti-TB drugs. Objective. In this research we studied the intracellular enzymes activity and bile formation function of the liver in rats of different ages in cases of tuberculostatic (isoniazid and rifampicin) affection and chromium (p...

  8. Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involved in bile acid homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Qiang; Chen, Xin-li; Wang, Chang-yuan; Liu, Qi; Sun, Hui-jun; Sun, Peng-yuan; Huo, Xiao-kui; Liu, Zhi-hao; Yao, Ji-hong; Liu, Ke-xin, E-mail: kexinliu@dlmedu.edu.cn

    2015-03-15

    Intrahepatic cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Appropriate regulation of bile acids in hepatocytes is critically important for protection against liver injury. In the present study, we characterized the protective effect of alisol B 23-acetate (AB23A), a natural triterpenoid, on alpha-naphthylisothiocyanate (ANIT)-induced liver injury and intrahepatic cholestasis in mice and further elucidated the mechanisms in vivo and in vitro. AB23A treatment dose-dependently protected against liver injury induced by ANIT through reducing hepatic uptake and increasing efflux of bile acid via down-regulation of hepatic uptake transporters (Ntcp) and up-regulation of efflux transporter (Bsep, Mrp2 and Mdr2) expression. Furthermore, AB23A reduced bile acid synthesis through repressing Cyp7a1 and Cyp8b1, increased bile acid conjugation through inducing Bal, Baat and bile acid metabolism through an induction in gene expression of Sult2a1. We further demonstrate the involvement of farnesoid X receptor (FXR) in the hepatoprotective effect of AB23A. The changes in transporters and enzymes, as well as ameliorative liver histology in AB23A-treated mice were abrogated by FXR antagonist guggulsterone in vivo. In vitro evidences also directly demonstrated the effect of AB23A on FXR activation in a dose-dependent manner using luciferase reporter assay in HepG2 cells. In conclusion, AB23A produces protective effect against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes. - Highlights: • AB23A has at least three roles in protection against ANIT-induced liver injury. • AB23A decreases Ntcp, and increases Bsep, Mrp2 and Mdr2 expression. • AB23A represses Cyp7a1 and Cyp8b1 through inducing Shp and Fgf15 expression. • AB23A increases bile acid metabolism through inducing Sult2a1 expression. • FXR activation is involved

  9. Alisol B 23-acetate protects against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes involved in bile acid homeostasis

    International Nuclear Information System (INIS)

    Meng, Qiang; Chen, Xin-li; Wang, Chang-yuan; Liu, Qi; Sun, Hui-jun; Sun, Peng-yuan; Huo, Xiao-kui; Liu, Zhi-hao; Yao, Ji-hong; Liu, Ke-xin

    2015-01-01

    Intrahepatic cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Appropriate regulation of bile acids in hepatocytes is critically important for protection against liver injury. In the present study, we characterized the protective effect of alisol B 23-acetate (AB23A), a natural triterpenoid, on alpha-naphthylisothiocyanate (ANIT)-induced liver injury and intrahepatic cholestasis in mice and further elucidated the mechanisms in vivo and in vitro. AB23A treatment dose-dependently protected against liver injury induced by ANIT through reducing hepatic uptake and increasing efflux of bile acid via down-regulation of hepatic uptake transporters (Ntcp) and up-regulation of efflux transporter (Bsep, Mrp2 and Mdr2) expression. Furthermore, AB23A reduced bile acid synthesis through repressing Cyp7a1 and Cyp8b1, increased bile acid conjugation through inducing Bal, Baat and bile acid metabolism through an induction in gene expression of Sult2a1. We further demonstrate the involvement of farnesoid X receptor (FXR) in the hepatoprotective effect of AB23A. The changes in transporters and enzymes, as well as ameliorative liver histology in AB23A-treated mice were abrogated by FXR antagonist guggulsterone in vivo. In vitro evidences also directly demonstrated the effect of AB23A on FXR activation in a dose-dependent manner using luciferase reporter assay in HepG2 cells. In conclusion, AB23A produces protective effect against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes. - Highlights: • AB23A has at least three roles in protection against ANIT-induced liver injury. • AB23A decreases Ntcp, and increases Bsep, Mrp2 and Mdr2 expression. • AB23A represses Cyp7a1 and Cyp8b1 through inducing Shp and Fgf15 expression. • AB23A increases bile acid metabolism through inducing Sult2a1 expression. • FXR activation is involved

  10. AM-2201 Inhibits Multiple Cytochrome P450 and Uridine 5′-Diphospho-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

    Directory of Open Access Journals (Sweden)

    Ju-Hyun Kim

    2017-03-01

    Full Text Available AM-2201 is a synthetic cannabinoid that acts as a potent agonist at cannabinoid receptors and its abuse has increased. However, there are no reports of the inhibitory effect of AM-2201 on human cytochrome P450 (CYP or uridine 5′-diphospho-glucuronosyltransferase (UGT enzymes. We evaluated the inhibitory effect of AM-2201 on the activities of eight major human CYPs (1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4 and six major human UGTs (1A1, 1A3, 1A4, 1A6, 1A9, and 2B7 enzymes in pooled human liver microsomes using liquid chromatography–tandem mass spectrometry to investigate drug interaction potentials of AM-2201. AM-2201 potently inhibited CYP2C9-catalyzed diclofenac 4′-hydroxylation, CYP3A4-catalyzed midazolam 1′-hydroxylation, UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-glucuronidation, and UGT2B7-catalyzed naloxone 3-glucuronidation with IC50 values of 3.9, 4.0, 4.3, and 10.0 μM, respectively, and showed mechanism-based inhibition of CYP2C8-catalyzed amodiaquine N-deethylation with a Ki value of 2.1 μM. It negligibly inhibited CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2D6, UGT1A1, UGT1A4, UGT1A6, and UGT1A9 activities at 50 μM in human liver microsomes. These in vitro results indicate that AM-2201 needs to be examined for potential pharmacokinetic drug interactions in vivo due to its potent inhibition of CYP2C8, CYP2C9, CYP3A4, UGT1A3, and UGT2B7 enzyme activities.

  11. Effect of cadmium pretreatment on liver regeneration after partial hepatectomy in rats

    International Nuclear Information System (INIS)

    Margeli, A.; Theocharis, S.; Skaltsas, S.; Skopelitou, A.; Kittas, C.; Mykoniatis, M.; Varonos, D.

    1994-01-01

    In this study we examined the effect of cadmium pretreatment, administered 24 h before partial hepatectomy, on the liver regenerative process in rats, at different time intervals. The rate of 3 H thymidine incorporation into hepatic DNA and the activity of the enzyme thymidine kinase were used as indices of liver proliferative capacity. Thymidine kinase, the rate-determining enzyme of DNA biosynthesis, was suppressed during the first hours following partial hepatectomy in the liver of cadmium pretreated animals. DNA biosynthesis was also strongly decreased in cadmium pretreated animals, by delaying the first peak of liver regeneration, compared with the partially hepatectomized ones. Biochemical parameters, mitotic index and proliferating cell nuclear antigen staining were also coestimated. The above data suggest that cadmium pretreatment suppressed the hepatic regenerative process, probably due to the inhibition of thymidine kinase. (orig./MG)

  12. Association between elevated coffee consumption and daily chocolate intake with normal liver enzymes in HIV-HCV infected individuals: results from the ANRS CO13 HEPAVIH cohort study.

    Science.gov (United States)

    Carrieri, M Patrizia; Lions, Caroline; Sogni, Philippe; Winnock, Maria; Roux, Perrine; Mora, Marion; Bonnard, Philippe; Salmon, Dominique; Dabis, François; Spire, Bruno

    2014-01-01

    We used longitudinal data from the ANRS CO13 HEPAVIH cohort study of HIV-HCV co-infected individuals to investigate whether polyphenol rich food intake through coffee and/or daily chocolate consumption could play a role in reducing liver enzymes levels. Longitudinal data collection included self-administered questionnaires and medical data (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) liver enzymes). Two analyses were performed to assess the association between coffee (≥3 cups a day) and daily chocolate intake and abnormal values of AST and ALT (AST or ALT >2.5 × upper normal limit (UNL)) (N=990) over time, after adjustment for known correlates. Logistic regression models based on generalized estimating equations were used to take into account the correlations between repeated measures and estimate adjusted odds ratio. After adjustment, patients reporting elevated coffee consumption and daily chocolate intake were less likely to present abnormal ALT (OR=0.65; p=0.04 and OR=0.57; p=0.04, for coffee and chocolate respectively), while only patients reporting elevated coffee consumption were less likely to have abnormal AST values (p=0.05). Nevertheless, the combined indicator of coffee and chocolate intake was most significantly associated with approximately 40% reduced risk of abnormal liver enzymes (p=0.003 for AST; p=0.002 for ALT). Elevated coffee consumption and daily chocolate intake appear to be associated with reduced levels of liver enzymes in HIV-HCV co-infected patients. Further experimental and observational research is needed to better understand the role that polyphenol intake or supplementation can play on liver disease and liver injury. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  13. Diagnostic performances of serum liver enzymes and cytokines in non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Hakan Turkon

    2015-03-01

    Full Text Available Objective:Non-alcoholic fatty liver disease (NAFLD is affecting people worldwide with increasing prevalence. Non-invasive tests are required for both diagnosis and staging of the disease. We aimed to evaluate diagnostic accuracy of routine liver enzymes and cytokines in NAFLD. Methods:A total of 88 cases, aged between 20 and 62 years, were included in the study. Serum ALT, AST, GGT, triglyceride, TNF-alpha, IL-6 and IL-8 were measured in 40 patients with NAFLD and in 48 healthy control patients with similar BMI and demographic characteristics. Diagnostic performances of serum biomarkers for diagnosis of NAFLD were evaluated with ROC analysis. Results:ALT and AST showed good diagnostic performance in predicting patients with NAFLD in the overall group (AUC=0.817; 95% CI[0.721-0.913], AUC=0.815;95% CI[0.718-0.911] respectively but in obese subjects ALT and AST showed poor performance (AUC=0.659;95% CI[0.478-0.841], AUC=0.680; 95% CI[0.498-0.861] respectively. Among cytokines TNF-alpha showed best performance in the diagnosis of NAFLD in both overall group and obese subjects (AUC=0.892; 95% CI[0.824- 0.959], AUC=0.858; 95% CI[0.739-0.977] respectively. The optimal cut off value for TNF-alpha was 10.65pg/ml with a sensitivity of 75% and a specificity of 93% in the overall group. IL-6 and IL-8 showed poor performance. Conclusion: TNF-alpha may be a good parameter for predicting patients with NAFLD. J Clin Exp Invest 2015;6 (1: 16-20

  14. Possible gasoline-induced chronic liver injury due to occupational malpractice in a motor mechanic: a case report.

    Science.gov (United States)

    Gunathilaka, Mahesh Lakmal; Niriella, Madunil Anuk; Luke, Nathasha Vihangi; Piyarathna, Chathura Lakmal; Siriwardena, Rohan Chaminda; De Silva, Arjuna Priyadarshin; de Silva, Hithanadura Janaka

    2017-07-03

    Hydrocarbon-induced occupational liver injury is a well-known clinical entity among petroleum industry workers. There are many types of hydrocarbon exposure, with inhalation being the most common. Hydrocarbon-induced occupational liver injury is a rarely suspected and commonly missed etiological agent for liver injury. We report a case of a non-petroleum industry worker with chronic liver disease secondary to hydrocarbon-induced occupational liver injury caused by chronic low-grade hydrocarbon ingestion due to occupational malpractice. A 23-year-old Sri Lankan man who was a motor mechanic presented to our hospital with decompensated cirrhosis. He had been chronically exposed to gasoline via inadvertent ingestion due to occupational malpractice. He used to remove gasoline from carburetors by sucking and failed to practice mouth washing thereafter. On evaluation, he had histologically proven established cirrhosis. A comprehensive history and workup ruled out other nonoccupational etiologies for cirrhosis. The patient's long-term occupational gasoline exposure and clinical course led us to a diagnosis of hydrocarbon-induced occupational liver injury leading to decompensated cirrhosis. Hydrocarbon-induced occupational liver injury should be considered as a cause when evaluating a patient with liver injury with possible exposure in relevant occupations.

  15. A new factor from enteric bacteria of rats amplifying induction of liver enzyme by glucocorticoid. Pt. 2

    International Nuclear Information System (INIS)

    Kido, Hiroshi; Higashi, Takao; Katanuma, Nobuhiko

    1977-01-01

    1) An amplifier of the action of glucocorticoid was purified from Proteus mirabilis as described previously. It was found that it amplified the induction of liver tyrosine aminotransferase by dexamethasone markedly with doses of dexamethasone that caused minimal enzyme induction, but had little effect with doses that caused maximal induction. Thus the amplification may represent a saving of glucocorticoid. The amplification of enzyme activity was brought about by increase in amount of enzyme. 2) The amplification was observed when the amplifier was administered before or with dexamethasone, but not when it was given 2 h after dexamethasone. These results and the finding that actinomycin D inhibited the amplification indicate that the amplifier does not act on the translational level of enzyme induction. 3) It was found that the amplifier increased both incorporation of [ 3 H]dexamethasone into the cytosol and binding of [ 3 H]dexamethasone to cytosol protein and that it decreased decay of the [ 3 H]dexamethasone protein complex. (orig.) [de

  16. The relationship between HbA(1c) and fasting plasma glucose in patients with increased plasma liver enzyme measurements

    DEFF Research Database (Denmark)

    Christiansen, R; Rasmussen, L Melholt; Nybo, H

    2012-01-01

    levels of increased liver enzyme concentrations. Methods:  Data from 10 065 patients with simultaneous measurement of HbA(1c) , venous fasting plasma glucose, alanine aminotransferase and γ-glutamyl transferase were extracted from our laboratory database. Correlations were investigated in four patient...

  17. Effect of Withania Somnifera Root Powder on the Levels of Circulatory Lipid Peroxidation and Liver Marker Enzymes in Chronic Hyperammonemia

    Directory of Open Access Journals (Sweden)

    B. Harikrishnan

    2008-01-01

    Full Text Available Withania somnifera (L Dunal (Solanaceae, commonly called Ashwagandha (Sanskrit is an Ayurvedic Indian medicinal plant, which has been widely used as a home remedy for several ailments. We have investigated the influence of W.somnifera root powder on the levels of circulatory ammonia, urea, lipid peroxidation products such as TBARS (thiobarbituric acid and reactive substances, HP (hydroperoxides and liver marker enzymes such as AST (aspartate transaminase, ALT (alanine transaminase and ALP (alkaline phosphatase, for its hepatoprotective effect in ammonium chloride induced hyperammonemia. Ammonium chloride treated rats showed a significant increase in the levels of circulatory ammonia, urea, AST, ALT, ALP, TBARS and HP. These changes were significantly decreased in rats treated with W.somnifera root powder and ammonium chloride. Our results indicate that W.somnifera offers hepatoprotection by influencing the levels of lipid peroxidation products and liver markers in experimental hyperammonemia and this could be due to (i the presence of alkaloids, withanolids and flavonoids, (ii normalizing the levels of urea and urea related compounds, (iii its free radical scavenging property and (iv its antioxidant property. The exact underlying mechanism is still unclear and further research needed.

  18. Changes in activities of adaptive liver enzymes in rats after non-lethal x-irradiation

    International Nuclear Information System (INIS)

    Toropila, M.; Ahlersova, E.; Ahlers, I.; Benova, K.

    1998-01-01

    The effect of a single dose of whole-body X-irradiation of 2.39 Gy (250 R) on the activities of selected adaptive rat liver enzymes and blood serum corticosterone concentrations was followed for a period of 28 days. Rats of Wistar strain SPF breeding (VELAZ Prague) were used. Both irradiated and control animals were fed in pairs with the same amount of feed as was consumed by irradiated animals in the pilot experiment. The feed intake of irradiated animals decreased significantly until the fourth day. During the rest of the experimental period no significant differences were recorded in feed intake between the experimental and control groups. The activity of tyrosine aminotransferase (TAT) in the liver of irradiated animals increased, with the exception of the initial period. Similar changes were recorded in the activity of tryptophane-2-3 dioxygenase (TO). A significant increase on the third day and a significant decrease from the seventh day after irradiation was recorded in the activity of aspartate aminotransferase (AST). Similar changes were observed with alanine aminotransferase (ALT). It is necessary to stress that the activity of this enzyme decreased also on the first day after irradiation. Until the third day there was a marked increase of serum corticosterone in the irradiated animals. The results point not only towards significant changes to the parameters observed, caused by a non-lethal irradiation dose, but also towards the importance of the nutritional regime, so-called paired feeding

  19. Acute-on-chronic liver failure due to thiamazole in a patient with hyperthyroidism and trilogy of Fallot: case report

    Science.gov (United States)

    2010-01-01

    Background Thiamazole is a widely used antithyroid agent that has been approved for the treatment of hyperthyroidism. Although thiamazole-induced hepatotoxicity is a main side effect, it may progress to liver failure in a very few cases. Case Presentation We described a 24-year-old patient with hyperthyroidism and trilogy of Fallot, who developed liver failure due to thiamazole. Liver biopsy showed intrahepatic cholestasis, mild inflammatory infiltrates, as well as significant fibrosis, indicating both acute and chronic liver injuries. Although a series of potent therapies were given, the patient deceased due to severe liver decompensation. Conclusions This case suggests that thiamazole-induced hepatotoxicity in the setting of advanced fibrosis increases the risk of poor outcome. Regular liver function monitoring during thiamazole therapy is therefore important. PMID:20707932

  20. The Effects of Exercise on Abdominal Fat and Liver Enzymes in Pediatric Obesity: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    González-Ruiz, Katherine; Ramírez-Vélez, Robinson; Correa-Bautista, Jorge Enrique; Peterson, Mark D; García-Hermoso, Antonio

    2017-08-01

    Despite the prevalence of obesity and the multiple position stands promoting exercise for the treatment of obesity and hepatic function, a meta-analytic approach has not previously been used to examine the effects in the pediatric population. The aim of the study was to determine the effectiveness of exercise interventions on abdominal fat, liver enzymes, and intrahepatic fat in overweight and obese youth. A computerized search was made using three databases. The analysis was restricted to studies that examined the effect of supervised exercise interventions on abdominal fat (visceral and subcutaneous fat), liver enzymes (alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase), and intrahepatic fat. Fourteen clinical trials (1231 youths) were eligible for inclusion in this systematic review and meta-analysis. Standardized mean difference [SMD] and 95% confidence intervals (CIs) were calculated. Exercise was associated with a significant reduction in visceral (SMD = -0.661; 95% CI, -0.976 to -0.346; p exercise programs that involve aerobic exercise longer than three sessions per week. This meta-analysis supports current recommendation for physical exercise, mainly aerobic, as an effective intervention for nonalcoholic fatty liver disease progression by targeting hepatic lipid composition, visceral and subcutaneous adipose tissue. Systematic review registration: PROSPERO CRD42016042163.

  1. Correlation of endothelin-1 concentration and angiotensin-converting enzyme activity with the staging of liver fibrosis.

    Science.gov (United States)

    Kardum, Dusko; Fabijanić, Damir; Lukić, Anita; Romić, Zeljko; Petrovecki, Mladen; Bogdanović, Zoran; Jurić, Klara; Urek-Crncević, Marija; Banić, Marko

    2012-06-01

    Increased serum angiotensin-converting enzyme (SACE) activity and serum concentration of endothelin-1 (ET-1) were found in liver cirrhosis. We investigated a correlation between the different stages of liver fibrosis and SACE activity and serum ET-1 concentration. Seventy patients with pathohistologically established chronic liver disease were divided in three groups according to Ishak criteria for liver fibrosis: minimal fibrosis (Ishak score 0-1, n =20), medium fibrosis (Ishak score 2-5, n=20) and cirrhosis (Ishak score 6, n=30). SACE activity and ET-1 concentration were determined using commercial ELISA kits. SACE activity and ET-1 concentrations were proportional to the severity of disease, the highest being in patients with liver cirrhosis. Maximal increase in SACE activity was found between minimal and medium fibrosis while maximal increase in ET-1 concentration was revealed between medium fibrosis and cirrhosis. The analysis of the Receiver Operating Characteristic (ROC) curve for SACE activity suggested a cut-off value to separate minimal from medium fibrosis at 59.00 U/L (sensitivity 100%, specificity 64.7%). The cut-off value for serum ET-1 concentration to separate medium fibrosis from cirrhosis was 12.4 pg/mL (sensitivity 96.8%, specificity 94.4%). A positive correlation between SACE activity and ET-1 concentration was registered (Spearman's ñ = 0.438, p = 0.004). Both SACE activity and ET-1 concentration were increased in all stages of liver fibrosis. Cut-off points for SACE activity and ET-1 concentration could be a biochemical marker for the progression of fibrosis. Positive correlation between SACE activity and ET-1 concentration might indicate their interaction in the development of liver cirrhosis.

  2. Translation of Angiotensin-Converting Enzyme 2 upon Liver- and Lung-Targeted Delivery of Optimized Chemically Modified mRNA

    Directory of Open Access Journals (Sweden)

    Eva Schrom

    2017-06-01

    Full Text Available Changes in lifestyle and environmental conditions give rise to an increasing prevalence of liver and lung fibrosis, and both have a poor prognosis. Promising results have been reported for recombinant angiotensin-converting enzyme 2 (ACE2 protein administration in experimental liver and lung fibrosis. However, the full potential of ACE2 may be achieved by localized translation of a membrane-anchored form. For this purpose, we advanced the latest RNA technology for liver- and lung-targeted ACE2 translation. We demonstrated in vitro that transfection with ACE2 chemically modified messenger RNA (cmRNA leads to robust translation of fully matured, membrane-anchored ACE2 protein. In a second step, we designed eight modified ACE2 cmRNA sequences and identified a lead sequence for in vivo application. Finally, formulation of this ACE2 cmRNA in tailor-made lipidoid nanoparticles and in lipid nanoparticles led to liver- and lung-targeted translation of significant amounts of ACE2 protein, respectively. In summary, we provide evidence that RNA transcript therapy (RTT is a promising approach for ACE2-based treatment of liver and lung fibrosis to be tested in fibrotic disease models.

  3. Acute-on-chronic liver failure due to thiamazole in a patient with hyperthyroidism and trilogy of Fallot: case report

    Directory of Open Access Journals (Sweden)

    Shen Chuan

    2010-08-01

    Full Text Available Abstract Background Thiamazole is a widely used antithyroid agent that has been approved for the treatment of hyperthyroidism. Although thiamazole-induced hepatotoxicity is a main side effect, it may progress to liver failure in a very few cases. Case Presentation We described a 24-year-old patient with hyperthyroidism and trilogy of Fallot, who developed liver failure due to thiamazole. Liver biopsy showed intrahepatic cholestasis, mild inflammatory infiltrates, as well as significant fibrosis, indicating both acute and chronic liver injuries. Although a series of potent therapies were given, the patient deceased due to severe liver decompensation. Conclusions This case suggests that thiamazole-induced hepatotoxicity in the setting of advanced fibrosis increases the risk of poor outcome. Regular liver function monitoring during thiamazole therapy is therefore important.

  4. The antioxidant effects of vitamin C on liver enzymes: aspartate aminotransferase, alanine aminotranferease, alkaline phosphatase and gamma-glutamyltransferase activities in rats under Paraquat insult

    Directory of Open Access Journals (Sweden)

    Benjamin Nnamdi Okolonkwo

    2013-06-01

    Full Text Available Paraquat (PQ is a bipyridylium herbicide; applied around trees in orchards and between crop rows to control broad-leaved and grassy weeds. Its oxidation results in the formation of superoxides which causes damage to cellular components. In this study, we determined the antioxidant effect vitamin C has on the liver enzymes [aspartate aminotransferase (SGOT, alanine aminotranferease (SGPT, alkaline phosphatase (ALP, and gamma-glutamyltransferase (GGT] of rats under this toxic insult. Male rats in groups (A, B, C and D were intraperitoneally injected with different sublethal increasing doses (0, 0.02, 0.04 and 0.06 g/kg body weigh of PQ respectively on monthly basis. Subsequently, the subgroups (A2, B2, C2 and D2 were given orally, 200 mg/L vitamin C, while the subgroups A1, B1, C1, and D1, received only water. Four animals per subgroup were decapitated on monthly basis and blood samples taken for enzyme assay. The parameters studied were - SGOT, SGPT, ALP and GGT - liver enzymes. The dose and time dependent PQ toxicity effect resulted in highly elevated Liver enzymes activities. The subgroups on vitamin C had significantly lower enzyme activities when compared to the same subgroups on only PQ insult. But the values were high when compared to the control subgroups (A1 and A2. These results were indication that vitamin C when given at moderate doses and maintained for a longer period could be a life saving adjunct to toxic insult.

  5. Computer tomographic findings in portal hypertension due to cirrhosis of the liver. Pt. 1

    International Nuclear Information System (INIS)

    Koester, O.; Kunz, R.; Fischer, P.; Lackner, K.; Koischwitz, D.; Bonn Univ.

    1983-01-01

    The CT findings in 80 patients with confirmed portal hypertension due to intrahepatic block were analysed retrospectively. The findings included ascites, hypo-dense areas in the liver, nodular or irregular liver contour, the inability of define intrahepatic portal vessels with narrow window settings, the so-called ''kissing'' sign and evidence of hepato-fugal collaterals and thickning of the wall of the oesophagus. Electronic measurements of various organs (liver, spleen) and vessel diameters (portal vein, superior mesenteric vein) provide parameters which permit classification of patients into the cirrhotic group, as compared with a control group. The statistical significance of this classification was checked by the Kolmogoroff-Smirnoff test. (orig.)

  6. Computer tomographic findings in portal hypertension due to cirrhosis of the liver. Pt. 1

    Energy Technology Data Exchange (ETDEWEB)

    Koester, O; Kunz, R; Fischer, P; Lackner, K; Koischwitz, D

    1983-06-01

    The CT findings in 80 patients with confirmed portal hypertension due to intrahepatic block were analysed retrospectively. The findings included ascites, hypo-dense areas in the liver, nodular or irregular liver contour, the inability of define intrahepatic portal vessels with narrow window settings, the so-called ''kissing'' sign and evidence of hepato-fugal collaterals and thickening of the wall of the oesophagus. Electronic measurements of various organs (liver, spleen) and vessel diameters (portal vein, superior mesenteric vein) provide parameters which permit classification of patients into the cirrhotic group, as compared with a control group. The statistical significance of this classification was checked by the Kolmogoroff-Smirnoff test.

  7. Hemolysis, Elevated Liver Enzymes, and Low Platelets, Severe Fetal Growth Restriction, Postpartum Subarachnoid Hemorrhage, and Craniotomy: A Rare Case Report and Systematic Review

    Directory of Open Access Journals (Sweden)

    Shadi Rezai

    2017-01-01

    Full Text Available Introduction. Hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome is a relatively uncommon but traumatic condition occurring in the later stage of pregnancy as a complication of severe preeclampsia or eclampsia. Prompt brain computed tomography (CT or magnetic resonance imaging (MRI and a multidisciplinary management approach are required to improve perinatal outcome. Case. A 37-year-old, Gravida 6, Para 1-0-4-1, Hispanic female with a history of chronic hypertension presented at 26 weeks and 6 days of gestational age. She was noted to have hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome accompanied by fetal growth restriction (FGR, during ultrasound evaluation, warranting premature delivery. The infant was delivered in stable condition suffering no permanent neurological deficit. Conclusion. HELLP syndrome is an uncommon and traumatic obstetric event which can lead to neurological deficits if not managed in a responsive and rapid manner. The central aggravating factor seems to be hypertension induced preeclamptic or eclamptic episode and complications thereof. The syndrome itself is manifested by hemolytic anemia, increased liver enzymes, and decreasing platelet counts with a majority of neurological defects resulting from hemorrhagic stroke or subarachnoid hemorrhage (SAH. To minimize adverse perinatal outcomes, obstetric management of this medical complication must include rapid clinical assessment, diagnostic examination, and neurosurgery consultation.

  8. Effects of Artemisia dracunculus Aqueous Extract on Blood Sugar, Serum Insulin, Triglyceride and Liver Enzymes in Fructose Drinking Water Male Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Shahraki

    2017-02-01

    Full Text Available Background Artemisia are various groups of plants which are used as an herbal medicine in all countries; the present study was designed to evaluate the effects of Artemisia dracunculus (AD leaves aqueous extract on blood sugar, serum insulin, and triglyceride and liver enzymes in Fructose Drinking water (FDW male rats. Methods At the beginning of experiment, 48 Wistar-albino male rats, weighing 200 - 250g were divided into control (C and FDW groups (n = 24. FDW group received FDW (10%, w/v for a month but control group did not receive any agents during the trial period. A half of control and FDW groups received AD L aqueous extract daily during trial period. At the end, animals were anesthetized, sacrificed and blood samples were collected from cervical vessels. Serum insulin, Blood glucose, insulin resistance index, triglyceride and liver enzymes were measured by ordinary methods. Obtained data were analyzed using SPSS-17 via one way ANOVA and Tukey tests. Results Our results showed that serum insulin, blood sugar, insulin resistance index, triglyceride, Aspartate amino transferase (AST and Alanine amino transferase (ALT values in FDW group significantly increased compared to C and C + E groups but these values in group FDW + E were significantly decreases compared to group FDW (P < 0.001. Conclusions Our findings demonstrated that AD L aqueous extract improves blood sugar, serum insulin, insulin resistance index and liver enzymes in rat model.

  9. Protective Effect of Hydroalcoholic Extract of Salvia officinalis L. against Acute Liver Toxicity of Acetaminophen in Mice

    Directory of Open Access Journals (Sweden)

    H. Foruozandeh

    2016-09-01

    Full Text Available Aims: The medical herbs play important roles in the treatment of liver diseases. In the traditional medicine, Salvia officinalis is highly used to heal a wide range of diseases. The aim of this study was to investigate the treatment effects of Saliva officinalis on hepatotoxicity due to acetaminophen. Materials & Methods: In the experimental study, 60 albino mice were studied. The rats were divided into 6 groups. The first, second, and third groups were physiological serum, crude extract of Saliva officinalis, and 500mg acetaminophen per 1Kg consumed as single dose, respectively. The fourth, fifth, and sixth groups received 5-day 125, 250, and 500mg per 1Kg extract of Saliva officinalis, respectively. Then, they received 500mg acetaminophen one hour after the last administration of extract. Blood sampling was done from the carotids of the rats 24hour later, and the levels of bilirubin and liver enzymes were measured. In addition, their liver tissues were studied. Data was analyzed by SPSS 16 software using one-way ANOVA. Findings: There were significant increases in the direct and complete bilirubin concentration and liver enzymes due to acetaminophen compared to control group (p<0.05. There were significant reductions in the direct and complete bilirubin and liver enzymes due to 125, 250, and 500mg per 1Kg of the extract of Saliva officinalis compared to control group (p<0.05. The results were confirmed by the histology studies. Conclusion: 250 and 500mg per 1Kg of Saliva officinalis potentially protect the damages caused by acetaminophen. In addition, they considerably improve the tissue damage and the biochemical indices in the liver damages.

  10. Quantitative liver functions in Turner syndrome with and without hormone replacement therapy

    DEFF Research Database (Denmark)

    Gravholt, Claus Højbjerg; Poulsen, H.E.; Ott, Peter

    2007-01-01

    Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes.......Studies have documented elevated levels of liver enzymes in many females with Turner syndrome (TS). Histology has shown a range of changes. Treatment with female hormone replacement therapy (HRT) reduces liver enzymes....

  11. [Inflammatory pancreatic disease due to enzyme autodigestion: an exceptional model of glandular crinophagy].

    Science.gov (United States)

    Sánchez-Fayos Calabuig, P; Martín Relloso, M Jesús; González Guirado, Agustina; Porres Cubero, Juan Carlos

    2007-01-01

    The exocrine pancreas is a functionally dangerous structure since it is exposed to digestion by its most aggressive enzymes (proteases, etc) despite self-protective measures such as the synthesis of some of these enzymes in the form of inactive zymogens (trypsinogen, etc.). We review inflammatory pancreatic disease by separately analyzing its classical forms of onset: acute and chronic pancreatitis (AP and CP). There is general consensus that the initial pathogenic event in AP is intraacinar activation of trypsinogen into trypsin, followed by that of the remaining proenzymes, giving rise to an unusual model of autophagic inflammation. In contrast, consensus is lacking on the initial pathogenic event in CP (toxic-metabolic lesion, oxidative stress, ductal hypertension, etc.?), although in some cases a sequence due to recurrent episodes of AP seems evident. The pathogenic features shared by both forms of the disease and which justify some recent attempts to formulate an overall explanation of the pathogenesis of pancreatitis are discussed. Such an explanation would place both forms of pancreatitis within the conceptual framework of an pancreatic disease due to enzyme autodigestion>.

  12. Regular exercise is associated with a reduction in the risk of NAFLD and decreased liver enzymes in individuals with NAFLD independent of obesity in Korean adults.

    Directory of Open Access Journals (Sweden)

    Ji Cheol Bae

    Full Text Available BACKGROUND: We evaluated the association of regular physical exercise with the presence of non-alcoholic fatty liver disease (NAFLD and liver enzymes in relation to obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional analysis was conducted in 72,359 healthy Korean adults without diabetes who participated in a comprehensive health check-up. Subjects who have been exercising regularly (more than 3 times per week, at least for 30 minutes each time and for consecutive 3 month were categorized into exercise group. All subjects were categorized into deciles based on their body mass index (BMI and we estimated the odds ratios (ORs for having NAFLD according to exercise regularity in each decile. The diagnosis of NAFLD was based on ultrasonography findings. Individuals with NAFLD (n = 19,921 were analyzed separately to evaluate ORs for having elevated liver enzymes based on regularity of exercise. The risk for NAFLD was significantly reduced in exercise group with age- and sex-adjusted ORs of 0.53-0.72 for all BMI deciles except at BMI categories of <19.6 and 20.7-21.6 kg/m(2. While no difference was seen in BMI between subjects in exercise and non-exercise group across the BMI deciles, the values of body fat percentage and metabolic risk factors differed. Among NAFLD patients, subjects in exercise group had a lower risk for having elevated liver enzymes with multivariable adjusted OR of 0.85 (95% CI 0.74-0.99, for AST and 0.74 (95% CI 0.67-0.81, for ALT than did subjects in non-exercise group. CONCLUSIONS/SIGNIFICANCE: Regular exercise was associated with a reduced risk for having NAFLD and decreased liver enzymes in patients with NAFLD, and this relationship was also independent of obesity.

  13. Vitamin D status, liver enzymes, and incident liver disease and mortality

    DEFF Research Database (Denmark)

    Skaaby, Tea; Husemoen, Lise Lotte Nystrup; Borglykke, Anders

    2014-01-01

    , alcohol consumption, smoking, physical activity, dietary habits, education, body mass index, and ALT). The risk of having a high level of ALT, AST, or GGT tended to be higher for lower vitamin D levels, although not statistically significant. In this general population study, vitamin D status...... was inversely associated with incident liver disease. Further studies are needed to determine whether patients in risk of developing impaired liver function should be screened for vitamin D deficiency for preventive purposes....

  14. Effect of curcumin and curcumin copper complex (1:1) on radiation-induced changes of anti-oxidant enzymes levels in the livers of Swiss albino mice

    International Nuclear Information System (INIS)

    Koiram, P.R.; Veerapur, V.P.; Mazhuvancherry, U.K.; Kunwar, A.; Mishra, B.; Barik, A.; Priyadarsini, I.K.

    2007-01-01

    The effect of mononuclear copper (II) complex of curcumin in 1:1 stoichiometry (hereafter referred to as complex) administered 30 mim before γ-irradiation (4.5 Gy) on alterations in antioxidant and Thiobarbituric acid reactive substances (TBARS) levels in livers was studied in comparison to curcumin at a dose of 50 mg/kg. The different antioxidants like glutathione (GSH), glutathione-S-transferase (GST), catalase, superoxide dismuatase (SOD), TBARS and total thiols were estimated in the liver homogenates excised at different time intervals (1, 2 and 4 h) post irradiation using colorimetric methods. There was a radiation-induced decrease in the levels of all the studied enzymes at 1 h post irradiation, while an increase was observed at later time points. Both curcumin and complex treatment in sham-irradiated mice decreased the levels of GSH and total thiols, whereas there was an increase in the levels of catalase, GST and SOD compared to normal control. Under the influence of irradiation, both curcumin and complex treatment protected the decline in the levels of GSH, GST, SOD, catalase and total thiols, and inhibited radiation-induced lipid peroxidation. Further, the complex was found to be more effective in protecting the enzymes at 1 h post irradiation compared to curcumin treated group. This may be due to the higher rate constants of the complex compared to curcumin for their reactions with various free radicals. (author)

  15. Effect of curcumin and curcumin copper complex (1:1) on radiation-induced changes of anti-oxidant enzymes levels in the livers of Swiss albino mice

    Energy Technology Data Exchange (ETDEWEB)

    Koiram, P R; Veerapur, V P; Mazhuvancherry, U K [Manipal Coll. of Pharmaceutical Sciences, Manipal (India); Kunwar, A; Mishra, B; Barik, A; Priyadarsini, I K [Bhabha Atomic Research Center, Mumbai (India)

    2007-05-15

    The effect of mononuclear copper (II) complex of curcumin in 1:1 stoichiometry (hereafter referred to as complex) administered 30 mim before {gamma}-irradiation (4.5 Gy) on alterations in antioxidant and Thiobarbituric acid reactive substances (TBARS) levels in livers was studied in comparison to curcumin at a dose of 50 mg/kg. The different antioxidants like glutathione (GSH), glutathione-S-transferase (GST), catalase, superoxide dismuatase (SOD), TBARS and total thiols were estimated in the liver homogenates excised at different time intervals (1, 2 and 4 h) post irradiation using colorimetric methods. There was a radiation-induced decrease in the levels of all the studied enzymes at 1 h post irradiation, while an increase was observed at later time points. Both curcumin and complex treatment in sham-irradiated mice decreased the levels of GSH and total thiols, whereas there was an increase in the levels of catalase, GST and SOD compared to normal control. Under the influence of irradiation, both curcumin and complex treatment protected the decline in the levels of GSH, GST, SOD, catalase and total thiols, and inhibited radiation-induced lipid peroxidation. Further, the complex was found to be more effective in protecting the enzymes at 1 h post irradiation compared to curcumin treated group. This may be due to the higher rate constants of the complex compared to curcumin for their reactions with various free radicals. (author)

  16. Drug-induced liver injury associated with HIV medications.

    Science.gov (United States)

    Jain, Mamta K

    2007-08-01

    Antiretroviral therapy (ART) for HIV infection frequently has been associated with elevated liver enzyme levels. Determining the cause of elevated liver enzyme levels in patients who have HIV is difficult because ART usually consists of three different drugs, patients may be taking additional hepatotoxic medications and patients who have HIV often suffer from other liver diseases. Several agents, however, are recognized as having noteworthy and specific patterns of toxicity. This article reviews the different HIV drug classes, incidence of elevated liver enzyme values by class and by individual drug, risk factors, specific toxicities, and possible mechanisms of injury.

  17. Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Perocco, Paolo [Department of Experimental Pathology, Cancerology Section, viale Filopanti 22, I-40126, University of Bologna, Bologna (Italy); Bronzetti, Giorgio [Institute of Biology and Agricultural Biotechnology - CNR Research Area, via Moruzzi, I-56124 Pisa (Italy); Canistro, Donatella; Sapone, Andrea; Affatato, Alessandra; Pozzetti, Laura; Broccoli, Massimiliano [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Valgimigli, Luca [Department of Organic Chemistry ' A. Mangini' , Viale Risorgimento 4, I-40127, Alma-Mater Studiorum, University of Bologna, Bologna (Italy); Pedulli, Gian Franco [Department of Organic Chemistry ' A. Mangini' , Viale Risorgimento 4, I-40127, Alma-Mater Studiorum, University of Bologna, Bologna (Italy); Iori, Renato [C.R.A - Research Institute for Industrial Crops, via di Corticella 133, I-40129 Bologna (Italy); Barillari, Jessica [Institute of Biology and Agricultural Biotechnology - CNR Research Area, via Moruzzi, I-56124 Pisa (Italy)]|[C.R.A - Research Institute for Industrial Crops, via di Corticella 133, I-40129 Bologna (Italy); Sblendorio, Valeriana [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Legator, Marvin S. [Department of Preventive Medicine and Community Health, Division of Environmental Toxicology, The University of Texas Medical Branch at Galveston, 700 Harborside Drive, Galveston, TX 77555-1110 (United States); Paolini, Moreno [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Abdel-Rahman, Sherif Z. [Department of Preventive Medicine and Community Health, Division of Environmental Toxicology, The University of Texas Medical Branch at Galveston, 700 Harborside Drive, Galveston, TX 77555-1110 (United States)]. E-mail: sabdelra@utmb.edu

    2006-03-20

    Epidemiological and animal studies linking high fruit and vegetable consumption to lower cancer risk have strengthened the belief that long-term administration of isolated naturally occurring dietary constituents could reduce the risk of cancer. In recent years, metabolites derived from phytoalexins, such as glucoraphanin found in broccoli and other cruciferous vegetables (Brassicaceae), have gained much attention as potential cancer chemopreventive agents. The protective effect of these micronutrients is assumed to be due to the inhibition of Phase-I carcinogen-bioactivating enzymes and/or induction of Phase-II detoxifying enzymes, an assumption that still remains uncertain. The protective effect of glucoraphanin is thought to be due to sulforaphane, an isothiocyanate metabolite produced from glucoraphanin by myrosinase. Here we show, in rat liver, that while glucoraphanin slightly induces Phase-II enzymes, it powerfully boosts Phase-I enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), nitrosamines and olefins. Induction of the cytochrome P450 (CYP) isoforms CYP1A1/2, CYP3A1/2 and CYP2E1 was confirmed by Western immunoblotting. CYP induction was paralleled by an increase in the corresponding mRNA levels. Concomitant with this Phase-I induction, we also found that glucoraphanin generated large amount of various reactive radical species, as determined by electron paramagnetic resonance (EPR) spectrometry coupled to a radical-probe technique. This suggests that long-term uncontrolled administration of glucoraphanin could actually pose a potential health hazard.

  18. Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver

    International Nuclear Information System (INIS)

    Perocco, Paolo; Bronzetti, Giorgio; Canistro, Donatella; Valgimigli, Luca; Sapone, Andrea; Affatato, Alessandra; Pedulli, Gian Franco; Pozzetti, Laura; Broccoli, Massimiliano; Iori, Renato; Barillari, Jessica; Sblendorio, Valeriana; Legator, Marvin S.; Paolini, Moreno; Abdel-Rahman, Sherif Z.

    2006-01-01

    Epidemiological and animal studies linking high fruit and vegetable consumption to lower cancer risk have strengthened the belief that long-term administration of isolated naturally occurring dietary constituents could reduce the risk of cancer. In recent years, metabolites derived from phytoalexins, such as glucoraphanin found in broccoli and other cruciferous vegetables (Brassicaceae), have gained much attention as potential cancer chemopreventive agents. The protective effect of these micronutrients is assumed to be due to the inhibition of Phase-I carcinogen-bioactivating enzymes and/or induction of Phase-II detoxifying enzymes, an assumption that still remains uncertain. The protective effect of glucoraphanin is thought to be due to sulforaphane, an isothiocyanate metabolite produced from glucoraphanin by myrosinase. Here we show, in rat liver, that while glucoraphanin slightly induces Phase-II enzymes, it powerfully boosts Phase-I enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), nitrosamines and olefins. Induction of the cytochrome P450 (CYP) isoforms CYP1A1/2, CYP3A1/2 and CYP2E1 was confirmed by Western immunoblotting. CYP induction was paralleled by an increase in the corresponding mRNA levels. Concomitant with this Phase-I induction, we also found that glucoraphanin generated large amount of various reactive radical species, as determined by electron paramagnetic resonance (EPR) spectrometry coupled to a radical-probe technique. This suggests that long-term uncontrolled administration of glucoraphanin could actually pose a potential health hazard

  19. [Postoperative Bile Leakage Following Liver Resection Due to Stenosis of a Choledochojejunostomy Anastomosis after Pancreaticoduodenectomy - A Case Report].

    Science.gov (United States)

    Nakayama, Yoshihito; Watanabe, Nobukazu; Akasaka, Harue

    2017-11-01

    We report a rare case of intractable bile leakage after liver resection due to stenosis of the anastomosis of a choledochojejunostomy after pancreaticoduodenectomy. A 65-year-old woman was diagnosed with pancreatic and right breast cancer, and underwent pancreaticoduodenectomy and right mastectomy with simultaneous axillary lymph node dissection. Adjuvant chemotherapy and follow-up were performed in our department. After 18 months, computed tomography revealed a liver metastasis of 2.5 cm in segment 8. Because the primary nest of liver metastasis was unknown and performing a biopsy was difficult due to the location, partial resection of the liver was performed. Pathological examination confirmed liver metastasis from the breast cancer. She was rehospitalized due to a right subdiaphragmatic abscess 33 days post-surgery. Abscess drainage revealed bile leakage, and the cause was believed to be stenosis of the anastomosis created by the choledochojejunostomy. Percutaneous transhepatic cholangiographic drainage was performed, and the bile leakage disappeared immediately. However, it was difficult to release the anastomotic stenosis by choledochoscopy; therefore, a retrograde drainage tube was placed in the hepatic duct using enteroscopy, and it formed an internal fistula. The patient has continued to undergo chemotherapy for recurrence in the remnant liver that was observed 16 months after the hepatectomy. In conclusion, when hepatic resection is performed after pancreaticoduodenectomy, attention should be paid to the possible occurrence of bile leakage.

  20. Liver enzymes serum levels in patients with chronic kidney disease on hemodialysis: a comprehensive review

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    Luís Henrique Bezerra Cavalcanti Sette

    2014-04-01

    Full Text Available We reviewed the literature regarding the serum levels of the enzymes aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase in patients with chronic kidney disease on hemodialysis with and without viral hepatitis. Original articles published up to January 2013 on adult patients with chronic kidney disease on hemodialysis were selected. These articles contained the words “transaminases” “aspartate aminotransferase” “alanine aminotransferase” “gamma glutamyl transferase,” “liver enzymes”, AND “dialysis” OR “hemodialysis”. A total of 823 articles were retrieved. After applying the inclusion and exclusion criteria, 49 articles were selected. The patients with chronic kidney disease on hemodialysis had reduced serum levels of aminotransferases due to hemodilution, lower pyridoxine levels, or elevated homocysteine levels. The chronic kidney disease patients on hemodialysis infected with the hepatitis C virus also had lower aminotransferase levels compared with the infected patients without chronic kidney disease. This reduction is in part due to decreased viremia caused by the dialysis method, the production of a hepatocyte growth factor and endogenous interferon-α, and lymphocyte activation, which decreases viral action on hepatocytes. Few studies were retrieved on gamma-glutamyl transferase serum levels; those found reported that there were no differences between the patients with or without chronic kidney disease. The serum aminotransferase levels were lower in the patients with chronic kidney disease on hemodialysis (with or without viral hepatitis than in the patients with normal renal function; this reduction has a multifactorial origin.

  1. Slow elimination of injured liver DNA bases of γ-irradiated old mice

    International Nuclear Information System (INIS)

    Gaziev, A.I.; Malakhov, L.V.; Fomenko, L.A.

    1982-01-01

    The paper presents a study of the elimination of injured bases from the liver DNA of old and young mice after their exposure to γ rays. The presented data show that if DNA from the liver of irradiated mice is treated with incision enzymes, its priming activity is increased. In the case of enzymatic treatment of DNA isolated 5 h after irradiation we find a great difference between the priming activity of the liver DNA of old and young mice. The reason for this difference is that the liver DNA of 20-month old mice 5 h after irradiation still has many unrepaired injured bases. These data indicated that the rate of incision of γ-injured DNA bases in the liver of old mice is lower than in the liver of young mice. In the liver of mice of different age the rate of restitution of DNA, single-strand breaks induced by γ rays in doses up to 100 Gy is the same. At the same time, the level of induced reparative synthesis of DNA in cells of an old organism is lower than in cells of a young organism. The obtained data suggest that reduction of the rate of elimination of modified bases from the cell DNA of 20-month old mice is due to reduction of the activity of the DNA repair enzymes or to restrictions in the chromatin in the access of these enzymes to the injured regions of DNA in the cells of old animals

  2. Liver dysfunction in patients with severe anorexia nervosa.

    Science.gov (United States)

    Rosen, Elissa; Sabel, Allison L; Brinton, John T; Catanach, Brittany; Gaudiani, Jennifer L; Mehler, Philip S

    2016-02-01

    Evaluation of liver dysfunction in patients with severe anorexia nervosa (AN) has typically been limited to small case series. We report an investigation into the admission characteristics and clinical outcomes associated with liver dysfunction in a large cohort of adults hospitalized for medical stabilization of severe AN. We retrospectively evaluated electronic medical records to quantify the cumulative incidence of elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT). We compared mean (±SD), frequencies (%), and median (IQR) values of clinical covariates of interest by incidence of liver enzyme elevation. The study included 181 adults, admitted for medical stabilization of AN, from October 1, 2008 to December 31, 2013. AST and ALT were mildly elevated in 27.6% of patients and severely elevated (more than three times the upper limit of normal) in 35.4% of patients. On admission, patients with severely elevated liver enzymes had a lower body mass index (BMI) (11.9 ± 1.8 kg/m(2) vs.13.3 ± 1.7 kg/m(2)), lower percentage ideal body weight (56.5% ± 7.7% vs. 63.5% ± 8.3%), and lower prealbumin (64% vs. 37%) compared with the rest of the cohort (p < 0.001). While hospitalized, patients with severely elevated liver enzymes more often developed hypoglycemia, hypophosphatemia, and experienced longer lengths of stay (p < 0.001). Elevated liver enzymes are common in our patient population with severe AN. Liver enzymes reached near normal values by the time of discharge. Severely elevated liver enzymes were associated with a lower BMI and the development of hypoglycemia. © 2015 Wiley Periodicals, Inc.

  3. Clinical efficacy of Qinggan Huashi Huoxue decoction combined with liver-protecting and enzyme-lowering drugs in treatment of alcoholic liver disease

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    YAO Zhishan

    2016-07-01

    Full Text Available ObjectiveTo investigate the clinical efficacy and safety of Qinggan Huashi Huoxue decoction combined with liver-protecting and enzyme-lowering drugs in the treatment of alcoholic liver disease (ALD. MethodsA total of 175 ALD patients who were admitted to The Second People′s Hospital of Tangshan from January 2012 to December 2015 were enrolled and randomly divided into treatment group (87 patients and control group (88 patients. The patients in the control group were asked to quit smoking and were given nutritional support and medications including polyene phosphatidylcholine, reduced glutathione, magnesium isoglycyrrhizinate, and ursodeoxycholic acid capsules, and those in the treatment group were given the self-made traditional Chinese medicine Qinggan Huashi Huoxue decoction in addition to the therapeutic regimen for the control group. During the three courses of treatment (12 weeks, the patients′ clinical symptoms and signs were observed, liver function [alanine aminotransferase (ALT, aspartate aminotransferase (AST, gamma-glutamyl transpeptidase (GGT, albumin (Alb, and total bilirubin (TBil] and blood lipids [total cholesterol (TC, triglyceride (TG, high-density lipoprotein (HDL, and low-density lipoprotein (LDL] were performed regularly, the results of routine blood tests and abdominal ultrasound findings were recorded regularly, and adverse events which occurred during treatment were recorded. The independent samples t-test was used for comparison of continuous data between groups, an analysis of variance with repeated measures was used to compare the differences at each time point between the two groups, and the chi-square test was used for comparison of categorical data between groups. ResultsAfter treatment, all patients achieved varying degrees of improvements in clinical symptoms and signs, which showed significant differences between the two groups at weeks 4, 8, and 12 of treatment (t=14.390, 10.487, and 13.547, all P

  4. Prevalence of abnormal serum liver enzymes in patients with type 2 diabetes mellitus: a cross-sectional study from China.

    Science.gov (United States)

    Chen, Shuang; Guo, Xiaofan; Chen, Yintao; Dong, Siyuan; Sun, Yingxian

    2016-11-01

    This cross-sectional study aimed to determine the prevalence of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in Chinese type 2 diabetic patients and identify contributing risk factors. This cross-sectional study was conducted in rural areas of China, and 1,198 type 2 diabetic patients with complete data were recruited. Elevated ALT and AST levels were defined as >40 U/L. Prevalence of abnormal liver enzymes was analyzed and multivariable analysis was used to identify independent risk factors. 10.3% and 6.1% diabetic patients had elevated ALT and elevated AST, respectively. The prevalence of elevated liver enzymes was gender-related; it was 13.8% in men and 7.5% in women for elevated ALT, and 7.4% in men and 3.1% in women for elevated AST. High triglyceride was positively associated with both elevated ALT (OR 1.80, 95% CI 1.08-3.01, p = 0.024) and elevated AST (OR 2.24, 95%CI 1.08-4.65, p = 0.031), while taking anti-diabetes medicine was inversely related to both elevated ALT (OR 0.48, 95% CI 0.29-0.80, p = 0.005) and elevated AST (OR 0.37, 95% CI 0.17-0.82, p = 0.014). The risk of elevated ALT in diabetic patients increased with the presence of obesity (OR 2.54, 95% CI 1.07-6.01, p = 0.034), and was lower in women (OR 0.37, 95% CI 0.19-0.72, p = 0.003). Hypertension (OR 4.33, 95% CI 1.41-13.30, p = 0.011), current drinking status (OR 2.90, 95% CI 1.21-6.96, p = 0.017) and national minority (OR 3.26, 95%CI 1.31-8.12, p = 0.011) were risk factors for elevated AST. A relatively high prevalence of abnormal serum liver enzymes in diabetic patients was demonstrated in China, especially in males. More attention should be paid to preventing liver injuries in diabetic patients.

  5. Honey can repairing damage of liver tissue due to protein energy malnutrition through induction of endogenous stem cells.

    Science.gov (United States)

    Prasetyo, R Heru; Hestianah, Eka Pramyrtha

    2017-06-01

    This study was to evaluate effect of honey in repairing damage of liver tissue due to energy protein malnutrition and in mobilization of endogenous stem cells. Male mice model of degenerative liver was obtained through food fasting but still have drinking water for 5 days. It caused energy protein malnutrition and damage of liver tissue. The administration of 50% (v/v) honey was performed for 10 consecutive days, while the positive control group was fasted and not given honey and the negative control not fasted and without honey. Observations of regeneration the liver tissue based on histologically examination, observation of Hsp70 expression, and homing signal based on vascular endothelial growth factor-1 (VEGF-1) expression using immunohistochemistry technique. Observation on expression of CD34 and CD45 as the marker of auto mobilization of hematopoietic stem cells using flow cytometry technique. There is regeneration of the liver tissue due to protein energy malnutrition, decrease of Hsp70 expression, increase of VEGF-1 expression, and high expression of CD34 and CD45. Honey can improve the liver tissue based on: (1) Mobilization of endogenous stem cells (CD34 and CD45); (2) Hsp70 and VEGF-1 expressions as regeneration marker of improvement, and (3) regeneration histologically of liver tissue.

  6. The Effects of Short-Term Intensive Exercise on Levels of Liver Enzymes and Serum Lipids in Kick Boxing Athletes

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    Ömer Kaynar

    2016-03-01

    Full Text Available Objective: In this study, it was aimed to evaluate the ef­fects of short-term intensive exercise on liver enzymes and serum lipid levels with kick boxing athletes. Methods: 23 voluntary athletes who were between the ages of 15-46 and who engaged in kick–boxing have tak­en place this study. Athletes were made to do 45 minutes of warming-up, breathing, and stretching and 50 minutes of technical and tactical practices and then they were made to do a training match, which is equal to a 2 min­utes 3 circuits (1 minute rest kick-box match. In venous blood samples which were taken from athletes before and after training, aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP and gamma glutamine transpeptidase (GGT, enzyme activity and total cholesterol, high-density lipoprotein-cholesterol (HDL-C, low density lipoprotein-cholesterol (LDL-C and triglycerides serum levels were analyzed via spectropho­tometric method in Beckman Coulter AU 5800 auto ana­lyzer. Body composition measurements of athletes were made with Tanita TBF 300 brand device, which works with bio-impedance analysis (BIA system. Results: As a result of our study, statistically increases in serum ALT, AST, ALP and GGT enzyme activities and in serum total cholesterol, HDL-C and LDL-C levels were detected following short-term intensive exercise, but no significant difference was observed in TG levels after in­tensive exercise. Conclusion: The blows to the abdomen during kickbox­ing sports competitions result in increased liver enzymes and increased serum lipids may occur to meet energy de­mand of the body during exercise.

  7. Upper digestive stenosis due to a hydatid cyst of the liver.

    Science.gov (United States)

    Jarrar, Mohamed Salah; Ben Hadj Khalifa, Mohamed Habib; Toumi, Radhouane; Ghrissi, Rafik; Elghali, Mohamed Amine; Khenissi, Abdelmajid; Hamila, Fehmi; Letaief, Rached

    2015-03-01

    The complications of the hydatid cyst of the liver are dominated by infection and rupture. The compression of adjacent organs (mainly the inferior vena cava, the portal vein and the bile ducts) can be seen, when the cyst is located in the dome, in the hilum or within the hepatic parenchyma. Upper digestive stenosis by compression of the duodenum by the hydatid cyst is an exceptional complication. A 63 year-old patient had, for two months, upper digestive stenosis associated with a sensation of weight in the right hypochondrium. Digestive endoscopy showed an extrinsic compression of the second portion of the duodenum. Biopsies were negative. Abdominal CT showed up a hydatid cyst in the segment VI of the liver, adhering to the duodenum, with an exo-vesiculation compressing it. The patient was operated on: There was a hydatid cyst of the right lateral sector compressing the duodenum. A partial intralamellar pericystectomy was performed. Hydatid cyst of the liver, a parasitic disease described as benign, may give mechanical complications related to compression of adjacent organs (especially the bile ducts and veins). Compression of the digestive tract is exceptional. This is due to the proximity of the cyst to the duodenum and the thickness of the cyst wall.

  8. [Jaundice and pathological liver values].

    Science.gov (United States)

    Schwarzenbach, Hans-Rudolf

    2013-06-05

    Jaundice corresponds to elevated bilirubin- levels, whereat one has to distinguish between direct and indirect serum-bilirubin. In the present Mini Review causes and differential diagnosis of jaundice are outlined. Ultrasound-diagnostic plays a major role in identifying intrahepatic or extrahepatic jaundice. Attention is given to the differential diagnosis of elevated liver enzymes in presence of jaundice, pointing out the distinction between hepatocellular and cholestatic parameters as well as the differentiation in acute or chronic increase. Moreover, the consequences of liver enzyme elevations including further diagnostic procedures, are highlighted. Finally, possibilities and limitations of modern diagnostic tests for liver fibrosis are briefly overviewed.

  9. Gemfibrozil modulates cytochrome P450 and peroxisome proliferation-inducible enzymes in the liver of the yellow European eel (Anguilla anguilla).

    Science.gov (United States)

    Lyssimachou, Angeliki; Thibaut, Rémi; Gisbert, Enric; Porte, Cinta

    2014-01-01

    The human lipid regulator gemfibrozil (GEM) has been shown to induce peroxisome proliferation in rodents leading to hepatocarcinogenesis. Since GEM is found at biological active concentrations in the aquatic environment, the present study investigates the effects of this drug on the yellow European eel (Anguilla anguilla). Eels were injected with different concentrations of GEM (0.1 to 200 μg/g) and sampled 24- and 96-h post-injection. GEM was shown to inhibit CYP1A, CYP3A and CYP2K-like catalytic activities 24-h post-injection, but at 96-h post-injection, only CYP1A was significantly altered in fish injected with the highest GEM dose. On the contrary, GEM had little effect on the phase II enzymes examined (UDP-glucuronyltransferase and glutathione-S-transferase). Peroxisome proliferation inducible enzymes (liver peroxisomal acyl-CoA oxidase and catalase) were very weakly induced. No evidence of a significant effect on the endocrine system of eels was observed in terms of plasmatic steroid levels or testosterone esterification in the liver.

  10. Distinct Prominent Roles for Enzymes of Plasmodium berghei Heme Biosynthesis in Sporozoite and Liver Stage Maturation

    Science.gov (United States)

    Matuschewski, Kai; Haussig, Joana M.

    2016-01-01

    Malarial parasites have evolved complex regulation of heme supply and disposal to adjust to heme-rich and -deprived host environments. In addition to its own pathway for heme biosynthesis, Plasmodium likely harbors mechanisms for heme scavenging from host erythrocytes. Elaborate compartmentalization of de novo heme synthesis into three subcellular locations, including the vestigial plastid organelle, indicates critical roles in life cycle progression. In this study, we systematically profile the essentiality of heme biosynthesis by targeted gene deletion of enzymes in early steps of this pathway. We show that disruption of endogenous heme biosynthesis leads to a first detectable defect in oocyst maturation and sporogony in the Anopheles vector, whereas blood stage propagation, colonization of mosquito midguts, or initiation of oocyst development occurs indistinguishably from that of wild-type parasites. Although sporozoites are produced by parasites lacking an intact pathway for heme biosynthesis, they are absent from mosquito salivary glands, indicative of a vital role for heme biosynthesis only in sporozoite maturation. Rescue of the first defect in sporogony permitted analysis of potential roles in liver stages. We show that liver stage parasites benefit from but do not strictly depend upon their own aminolevulinic acid synthase and that they can scavenge aminolevulinic acid from the host environment. Together, our experimental genetics analysis of Plasmodium enzymes for heme biosynthesis exemplifies remarkable shifts between the use of endogenous and host resources during life cycle progression. PMID:27600503

  11. The expression and activity of antioxidant enzymes in the liver of rats exposed to high-fructose diet in the period from weaning to adulthood.

    Science.gov (United States)

    Glban, Alhadi M; Vasiljević, Ana; Veličković, Nataša; Nikolić-Kokić, Aleksandra; Blagojević, Duško; Matić, Gordana; Nestorov, Jelena

    2015-08-30

    Increased fructose consumption correlates with rising prevalence of various metabolic disorders, some of which were linked to oxidative stress. The relationship between fructose consumption and oxidative stress is complex and effects of a fructose-rich diet on the young population have not been fully elucidated. The aim of this study was to investigate whether high-fructose diet applied in the period from weaning to adulthood induces oxidative stress in the liver, thus contributing to induction or aggravation of metabolic disturbances in later adulthood. To that end we examined the effects of high-fructose diet on expression and activity of antioxidant enzymes, markers of lipid peroxidation and protein damage in the liver as the main fructose metabolizing tissue. High-fructose diet increased only SOD2 (mitochondrial manganese superoxide dismutase) activity, with no effect on other antioxidant enzymes, lipid peroxidation or accumulation of damaged proteins in the liver. The results show that fructose-induced metabolic disturbances could not be attributed to oxidative stress, at least not at young age. The absence of oxidative stress in the liver observed herein implies that young organisms are capable of maintaining redox homeostasis when challenged by fructose-derived energy overload. © 2014 Society of Chemical Industry.

  12. Honey can repairing damage of liver tissue due to protein energy malnutrition through induction of endogenous stem cells

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    R. Heru Prasetyo

    2017-06-01

    Full Text Available Aim: This study was to evaluate effect of honey in repairing damage of liver tissue due to energy protein malnutrition and in mobilization of endogenous stem cells. Materials and Methods: Male mice model of degenerative liver was obtained through food fasting but still have drinking water for 5 days. It caused energy protein malnutrition and damage of liver tissue. The administration of 50% (v/v honey was performed for 10 consecutive days, while the positive control group was fasted and not given honey and the negative control not fasted and without honey. Observations of regeneration the liver tissue based on histologically examination, observation of Hsp70 expression, and homing signal based on vascular endothelial growth factor-1 (VEGF-1 expression using immunohistochemistry technique. Observation on expression of CD34 and CD45 as the marker of auto mobilization of hematopoietic stem cells using flow cytometry technique. Results: There is regeneration of the liver tissue due to protein energy malnutrition, decrease of Hsp70 expression, increase of VEGF-1 expression, and high expression of CD34 and CD45. Conclusion: Honey can improve the liver tissue based on: (1 Mobilization of endogenous stem cells (CD34 and CD45; (2 Hsp70 and VEGF-1 expressions as regeneration marker of improvement, and (3 regeneration histologically of liver tissue.

  13. Independent and supra-additive effects of alcohol consumption, cigarette smoking, and metabolic syndrome on the elevation of serum liver enzyme levels.

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    Eun Young Park

    Full Text Available We investigated the independent and combined effects of alcohol consumption, cigarette smoking and metabolic syndrome on abnormal liver function, i.e., the elevation of serum liver enzyme levels. Participants of a Korean population-based prospective cohort aged ≥30 years without liver disease, diabetes, or cardiovascular diseases were included. Information on alcohol consumption, smoking status, and metabolic syndrome, defined as per the criteria of the Adult Treatment Panel III, were applied to evaluate their impact on serum levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT, and gamma-glutamyl transferase (GGT. Alcohol consumption, cigarette smoking and metabolic syndrome were the significant individual factors that elevated serum liver enzyme levels. Supra-additive effects of metabolic syndrome and either alcohol consumption or cigarette smoking were also identified. The combination of heavy drinking (≥24 g/day and metabolic syndrome conferred an effect that was higher than the sum of the two individual effects (Synergic Index (SI: AST, 2.37 [1.20-4.67]; GGT, 1.91 [1.17-3.13]. Only GGT level (odds ratio 6.04 [3.68-9.94], SI 2.33 [1.24-4.41] was significantly elevated when the effect of moderate drinking (20 pack years, 1.80 for ≥24 g/day and ≤20 pack years, 2.03 for ≥24 g/day and >20 pack years, while only the combined effect of drinking ≥24 g/day and smoking >20 pack years elevated the AST level (SI 4.55 [3.12-6.61]. The combined effect of cigarette smoking and metabolic syndrome was not supra-additive. To prevent fatty liver disease and other related diseases, a multifactorial prevention strategy that includes limited alcohol consumption, smoking cessation and rectification of adverse metabolic profiles is required.

  14. A case of probable esomeprazole-induced transient liver injury in a pregnant woman with hyperemesis

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    Thomas B

    2016-12-01

    Full Text Available Binny Thomas,1-3 Mahmoud Mohamed,1,3,4 Moza Al Hail,1-3 Fatma Alzahra Y Awwad,1 Ramy M Wahba,1 Sabir B Hassan,1 Khalid Omar,1 Wessam El Kassem,1 Palivalappila Abdul Rouf1 1Hamad Medical Corporation, Doha, Qatar; 2Robert Gordon University, Aberdeen, Scotland, UK; 3Qatar University, Doha, 4Weill Cornell Medical College, Ar-Rayyan, Qatar Abstract: We report a case of 22-year-old primigravida presented to Women’s Hospital – Hamad Medical Corporation emergency with severe epigastric pain, nausea, and vomiting. On admission, she was dehydrated with remarkably worsening symptoms. Laboratory findings revealed significantly elevated liver enzymes with unknown etiology. Her past medical history showed an admission for nausea and vomiting 3 weeks previously and she was discharged on antiemetics, and esomeprazole for the first time. Due to the predominantly elevated liver enzymes, the clinical pharmacist discussed the possibility of esomeprazole-induced adverse effects and suggested to suspend esomeprazole based on the evidence from literature review. The liver enzymes showed a substantial improvement within days after the discontinuation of the drug; however, a rechallenge was not done since it could have adversely affected the mother or the fetus. Using the Naranjo Adverse Drug Reaction Probability scales, the adverse reaction due to esomeprazole was classified as “probably”. Keywords: hyperemesis, drug-induced liver injury, esomeprazole, adverse drug reaction, ADR, proton pump inhibitor

  15. The effect of fenbuconazole on cell proliferation and enzyme induction in the liver of female CD1 mice

    International Nuclear Information System (INIS)

    Juberg, Daland R.; Mudra, Daniel R.; Hazelton, George A.; Parkinson, Andrew

    2006-01-01

    Fenbuconazole, a triazole fungicide, has been associated with an increase in the incidence of liver adenomas in female mice following long-term dietary exposure. The aim of this study was to evaluate whether the mode of action for liver tumor formation by fenbuconazole is similar to that of phenobarbital. Treatment of CD1 mice with 0, 20, 60, 180 or 1300 ppm fenbuconazole for up to 4 weeks caused a dose-dependent increase in liver weight that was associated with centrilobular hepatocellular hypertrophy, cytoplasmic eosinophilia and panlobular hepatocellular vacuolation, as well as an initial increase in the cell proliferation labeling index. Fenbuconazole also caused a dose-dependent increase in liver microsomal cytochromes b 5 and P450 and the levels of immunoreactive CYP2B10 and its associated activity 7-pentoxyresorufin O-dealkylation (PROD). Treatment of mice with 1000 ppm phenobarbital elicited the same effects as treatment of mice with 1300 ppm fenbuconazole, except that phenobarbital was more effective than fenbuconazole at inducing PROD activity, even though fenbuconazole induced CYP2B10 to the same extent as did phenobarbital. This difference was attributed to the ability of fenbuconazole to bind tightly to CYP2B10 and partially mask its catalytic activity in liver microsomes, which is characteristic of several azole-containing drugs. All hepatocellular changes and induced enzyme activity returned to control levels within 4 weeks of discontinuing treatment with fenbuconazole or phenobarbital, indicating that the observed changes were fully reversible. We conclude that fenbuconazole is a phenobarbital-type inducer of mouse liver cytochrome P450, and the mode of action by which fenbuconazole induces liver adenomas in mice is similar to that of phenobarbital

  16. Actions of p-synephrine on hepatic enzyme activities linked to carbohydrate metabolism and ATP levels in vivo and in the perfused rat liver.

    Science.gov (United States)

    Maldonado, Marcos Rodrigues; Bracht, Lívia; de Sá-Nakanishi, Anacharis Babeto; Corrêa, Rúbia Carvalho Gomes; Comar, Jurandir Fernando; Peralta, Rosane Marina; Bracht, Adelar

    2018-01-01

    p-Synephrine is one of the main active components of the fruit of Citrus aurantium (bitter orange). Extracts of the bitter orange and other preparations containing p-synephrine have been used worldwide to promote weight loss and for sports performance. The purpose of the study was to measure the action of p-synephrine on hepatic enzyme activities linked to carbohydrate and energy metabolism and the levels of adenine mononucleotides. Enzymes and adenine mononucleotides were measured in the isolated perfused rat liver and in vivo after oral administration of the drug (50 and 300 mg/kg) by using standard techniques. p-Synephrine increased the activity of glycogen phosphorylase in vivo and in the perfused liver. It decreased, however, the activities of pyruvate kinase and pyruvate dehydrogenase also in vivo and in the perfused liver. p-Synephrine increased the hepatic pools of adenosine diphosphate and adenosine triphosphate. Stimulation of glycogen phosphorylase is consistent with the reported increased glycogenolysis in the perfused liver and increased glycemia in rats. The decrease in the pyruvate dehydrogenase activity indicates that p-synephrine is potentially capable of inhibiting the transformation of carbohydrates into lipids. The capability of increasing the adenosine triphosphate-adenosine diphosphate pool indicates a beneficial effect of p-synephrine on the cellular energetics. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Effect of Titanium Dioxide Nanoparticles on The Amount of Blood Cells and Liver Enzymes in Wistar Rats

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    Rezaei Zarchi

    2011-11-01

    Full Text Available Introduction: Considering the development of nanotechnology and extensive use of nano-materials are in different fields of industry, it is necessary to investigate their destructive effects on biological systems. Titanium dioxide(TiO2 is used in the production of different dyes, cosmetics, ceramics, photocatalysts, water and sewage treatment and a lot of other products. In the present study, the effect of TiO2 on the number of blood cells and the activity of liver enzymes of rat was assessed. Methods: Concentrations of 50, 100 and 500 mg/Kg TiO2 nanoparticles (25 nm size in distilled water were administered orally to Wistar rats for 14 days and some blood factors were studied on the blood samples collected. Results: Results showed that TiO2 nanoparticles cause different changes in blood cells, and the changes were significant for some of them such as white blood cells (lymphocytes, monocytes, eosinophils and basophils. Decreased number of red blood cells and increased level of liver enzymes was also observed after the administration of different concentrations of TiO2, which proves the toxic effects of TiO2 on the body. Conclusion: Results of the present study proved the toxicity of TiO2 nanoparticles on the living organisms. So, further studies are recommended to predict TiO2 toxicity.

  18. Percutaneous Liver Biopsy after Living Donor Liver Transplantation Resulting in Fulminant Hepatic Failure: The First Reported Case of Hepatic Compartment Syndrome

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    Nicholas N. Nissen

    2010-01-01

    Full Text Available A 28-year-old female who underwent live donor liver transplantation 3 years prior presented after percutaneous liver biopsy with abdominal and shoulder pain, nausea, vomiting, and elevated liver enzymes. Computed tomography (CT showed an intrahepatic and subcapsular hematoma. There was a progressive increase in liver enzymes, bilirubin, and INR and a decline in hemoglobin. Subsequent CT imaging revealed flattening of the portal vein consistent with compression by the enlarging hematoma. Liver failure ensued and the patient required urgent retransplantation. The explant demonstrated ischemic necrosis of greater than 90% of the liver parenchyma. We report this case of “Hepatic Compartment Syndrome” leading to fulminant hepatic failure.

  19. Selective Activation of N,N'-Diacyl Rhodamine Pro-fluorophores Paired with Releasing Enzyme, Porcine Liver Esterase (PLE).

    Science.gov (United States)

    Abney, Kristopher K; Ramos-Hunter, Susan J; Romaine, Ian M; Godwin, J Shawn; Sulikowski, Gary A; Weaver, Charles David

    2018-04-21

    This study reports the synthesis and testing of a family of rhodamine pro-fluorophores and an enzyme capable of converting pro-fluorophores to Rhodamine 110. We prepared a library of simple N,N'-diacyl rhodamines and investigated Porcine Liver Esterase (PLE) as an enzyme to activate rhodamine-based pro-fluorophores. A PLE-expressing cell line generated an increase in fluorescence rapidly upon pro-fluorophore addition demonstrating the rhodamine pro-fluorophores are readily taken up and fluorescent upon PLE-mediated release. Rhodamine pro-fluorophore amides trifluoroacetamide (TFAm) and proponamide (PAm) appeared to be the best substrates using a cell-based assay using PLE expressing HEK293. Our pro-fluorophore series showed diffusion into live cells and resisted endogenous hydrolysis. The use of our engineered cell line containing the exogenous enzyme PLE demonstrated the rigorousness of amide masking when compared to cells not containing PLE. This simple and selective pro-fluorophore rhodamine pair with PLE offers the potential to be used in vitro and in vivo fluorescence based assays. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Tekatas, Demet D; Bahcecioglu, Ibrahim H; Ispiroglu, Murat; Sahin, Abdurrahman; Ilhan, Necip; Yalniz, Mehmet; Demirel, Ulvi

    2016-01-01

    In this study, we aimed to investigate the histological and clinical effect of angiotensin-converting enzyme (ACE) and ACE gene polymorphism in nonalcoholic fatty liver disease (NAFLD) and their roles in the progression of the disease. Liver function tests, body mass index, waist circumference, lipid parameters, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), homeostasis model assessment-IR (HOMA-IR), ACE, and ACE gene polymorphism were evaluated in the NAFLD group and control group. The study group was evaluated by dividing the group into four subgroups by ACE gene polymorphism (D/D homozygous, I/I homozygous, D/I heterozygous, I/D heterozygous). Liver biopsies were evaluated according to Brunt Classification. A total of 31 patients who were diagnosed with NAFLD and 40 healthy individuals were included in the study. The ACE level was found to be 11.69 ± 1.99 in the NAFLD group and 11.52 ± 1.72 in the control group (p = 0.70). There was a negative correlation between ACE levels and HOMA-IR levels (p = 0.008, r= -0.512). Biochemical parameters were not different among ACE gene polimorphism subgroups, except FBG (between D/D, I/D and D/I, I/D; p = 0.02). When the ACE levels were compared in terms of grade and stage, no significant difference was found (for stage and grade p = 0.68). The ACE gene polymorphism subgroups did not differ by histopathologic findings; grade and stage (for grade p = 0.42, for stage p = 0.92). In this study, we could not find a correlation of ACE and ACE gene polymorphism with metabolic risk factors and the disease severity in NAFLD. Tekatas DD, Bahcecioglu IH, Ispiroglu M, Sahin A, Ilhan N, Yalniz M, Demirel U. Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(2):137-142.

  1. The impact of longitudinal intestinal lengthening and tailoring on liver function in short bowel syndrome.

    Science.gov (United States)

    Reinshagen, K; Zahn, K; Buch, C von; Zoeller, M; Hagl, C I; Ali, M; Waag, K-L

    2008-08-01

    Short bowel syndrome is a functional or anatomic loss of major parts of the small bowel leading to severe malnutrition. The limiting factor for the survival of these patients remains parenteral nutrition-related liver damage leading to end-stage liver failure. Longitudinal intestinal lengthening and tailoring (LILT) has been proven to enhance peristalsis, to decrease bacterial overgrowth and to extend the mucosal contact time for the absorption of nutrients. The aim of this study was to show the impact of LILT on the development of parenteral nutrition-related liver damage. A cohort of 55 patients with short bowel syndrome managed with LILT in our institution between 1987 and 2007 was retrospectively reviewed. LILT was performed at a mean age of 24 months (range 4 - 150 months). Mean follow-up time was 83.76 months (range 5 - 240 months). We obtained reliable data from 31 patients with regard to liver enzymes and function parameters in blood samples before LILT and at the present time. Liver biopsy was performed in 14 patients prior to LILT. Liver enzymes ALAT (mean 121 U/l), ASAT (mean 166 U/l) and bilirubin (mean 2.49 mg/dl) were elevated preoperatively in 27/31 children. After the lengthening procedure, ALAT (mean 50 U/l), ASAT (mean 63 U/l) and bilirubin (mean 1.059 mg/dl) normalized except in 5 of 8 patients who could not be weaned from parenteral nutrition after LILT. Liver function parameters such as the international normal ratio (INR) were slightly elevated in 5/31 patients. Albumin was generally low, probably due to parenteral nutrition. Liver biopsy was performed in 14 patients preoperatively, showing 4 patients with low-grade, 6 patients with intermediate and 4 patients with high-grade fibrosis. End-stage liver disease with cirrhosis was an exclusion criterion for LILT. All patients with liver fibrosis showed a normalization of liver enzymes when they were weaned from parenteral nutrition. But patients with higher grade liver fibrosis tend to develop

  2. Effects of dietary probiotic supplementation on LXRα and CYP7α1 gene expression, liver enzyme activities and fat metabolism in ducks.

    Science.gov (United States)

    Huang, Z; Mu, C; Chen, Y; Zhu, Z; Chen, C; Lan, L; Xu, Q; Zhao, W; Chen, G

    2015-04-01

    1. The objective of this study was to investigate the effects of dietary probiotic supplementation on liver X receptor alpha (LXRα) and cholesterol 7α-hydroxylase (CYP7α1) mRNA levels, protein enzymatic activities and fat metabolism in Cherry Valley Pekin ducks. 2. A total of 750 one-day-old Cherry Valley Pekin ducks were randomly divided into 5 groups with three replicates of 50 ducks each in a completely randomised experiment. Each group was fed on a basal diet supplemented with 0, 500, 1000, 1500 or 2000 mg probiotics/kg. 3. Body rate and feed conversion ratio were highest and abdominal subcutaneous fat % was lowest at 1000 mg probiotic/kg. 4. The mRNA levels of LXRα and CYP7α1 in liver tissue was estimated by RT-PCR; serum triglyceride (TG) and total cholesterol (TC) concentrations were measured by ELISA. 5. The expression levels and enzyme activity of LXRα and CYP7α1 increased in conjunction with decreases in TG and TC concentrations following probiotic supplementation to a maximum at 1000 mg probiotics/kg and decreased thereafter. 6. It is concluded that dietary probiotics can enhance LXRα and CYP7α1 enzyme activities in the liver and reduce lipid concentrations and fat deposition in ducks.

  3. CT values of fatty liver due to L-asparaginase administration

    Energy Technology Data Exchange (ETDEWEB)

    Muraki, Kotaro; Kubo, Kazuaki; Hamamoto, Kazuko; Ueda, Kazuhiro; Kashiwado, Kozo; Ito, Katsuhide (Hiroshima Red Cross Hospital (Japan))

    1984-02-01

    Chemotherapy involving L-asparaginase was performed on a 9-year-old female child with malignant lymphoma, and a 3-year-old male child and a 14-year-old female child with acute lymphatic leukemia, and the course of L-asparaginase-induced fatty liver was followed up primarily by CT findings. In all 3 cases, L-asparaginase administration caused a marked fatty liver characterized by a diffuse cold area of the liver and a decrease in the value of the liver (liver/spleen<1) on CT. Hypoproteinemia, hypofibrinogenemia and elevations of GOT and GPT were simultaneously observed, but marked anemia, pancreatitis, decreased glucose tolerance and central nervous disorder did not occur. Recovery of fatty liver was slower in CT findings than in blood biochemistry, taking about 4 weeks.

  4. Systematic errors in respiratory gating due to intrafraction deformations of the liver

    International Nuclear Information System (INIS)

    Siebenthal, Martin von; Szekely, Gabor; Lomax, Antony J.; Cattin, Philippe C.

    2007-01-01

    This article shows the limitations of respiratory gating due to intrafraction deformations of the right liver lobe. The variability of organ shape and motion over tens of minutes was taken into account for this evaluation, which closes the gap between short-term analysis of a few regular cycles, as it is possible with 4DCT, and long-term analysis of interfraction motion. Time resolved MR volumes (4D MR sequences) were reconstructed for 12 volunteers and subsequent non-rigid registration provided estimates of the 3D trajectories of points within the liver over time. The full motion during free breathing and its distribution over the liver were quantified and respiratory gating was simulated to determine the gating accuracy for different gating signals, duty cycles, and different intervals between patient setup and treatment. Gating effectively compensated for the respiratory motion within short sequences (3 min), but deformations, mainly in the anterior inferior part (Couinaud segments IVb and V), led to systematic deviations from the setup position of more than 5 mm in 7 of 12 subjects after 20 min. We conclude that measurements over a few breathing cycles should not be used as a proof of accurate reproducibility of motion, not even within the same fraction, if it is longer than a few minutes. Although the diaphragm shows the largest magnitude of motion, it should not be used to assess the gating accuracy over the entire liver because the reproducibility is typically much more limited in inferior parts. Simple gating signals, such as the trajectory of skin motion, can detect the exhalation phase, but do not allow for an absolute localization of the complete liver over longer periods because the drift of these signals does not necessarily correlate with the internal drift

  5. Effects of whole-body γ-irradiation on lipid peroxidation and anti-oxidant enzymes in the liver of N-nitrosodiethylamine-treated mice

    International Nuclear Information System (INIS)

    Grudzinski, I.P.; Frankiewicz-Jozko, A; Gajewska, J.; Szczypka, M.; Szymanski, A.

    2000-01-01

    B6c3F1 mice were treated per os with either normal saline or N-nitrosodiethylamine (NDEA) (0.01, 0.1, 1.0 or 5.0 mg/kg body weight) daily for 21 days. On day 22 nd of the experiment , the animals were whole-body γ-irradiated (10 Gy) and examined at 3.5 days post-radiation exposure. Pretreatment of mice with NDEA at the lowest dosage (0.01 and 0.1 mg/kg) increased thiobarbituric acid-reactive substances (TBARS) and catalase (CAT) activity in the liver. Since the agent at the highest doses (1.0 and 5.0 mg/kg) did not have any effects on TBARS, it was associated with the selective increase of thiol (SH) groups and GSH-linked anti-oxidant enzyme activities such as glutathione peroxidase (GPX), transferase (GST) and reductase (GR). γ-irradiation decreased TBARS and increased superoxide dismutase (SOD) and GPX activity in NDEA-treated mice. Simultaneously, γ-rays did not have any effects on GST and GR enzymes, and it slightly decreased SH groups and CAT activity. Results of the present study indicate that NDEA can promote lipid peroxidation in mice liver. γ-irradiation of mice at a dose of 10 Gy modifies the activity of hepatic anti-oxidant enzymes, which in turn can lead to the reduction of NDEA-induced lipid peroxidation and/or pro-oxidant shift(s). The anti-oxidant enzymes such as SOD and GPX are suggested to be mainly involved in this process. (author)

  6. CT values of fatty liver due to L-asparaginase administration

    International Nuclear Information System (INIS)

    Muraki, Kotaro; Kubo, Kazuaki; Hamamoto, Kazuko; Ueda, Kazuhiro; Kashiwado, Kozo; Ito, Katsuhide

    1984-01-01

    Chemotherapy involving L-asparaginase was performed on a 9-year-old female child with malignant lymphoma, and a 3-year-old male child and a 14-year-old female child with acute lymphatic leukemia, and the course of L-asparaginase-induced fatty liver was followed up primarily by CT findings. In all 3 cases, L-asparaginase administration caused a marked fatty liver characterized by a diffuse cold area of the liver and a decrease in the value of the liver (liver/spleen<1) on CT. Hypoproteinemia, hypofibrinogenemia and elevations of GOT and GPT were simultaneously observed, but marked anemia, pancreatitis, decreased glucose tolerance and central nervous disorder did not occur. Recovery of fatty liver was slower in CT findings than in blood biochemistry, taking about 4 weeks. (Chiba, N.)

  7. Expression of Enzymes that Metabolize Medications

    Science.gov (United States)

    Wotring, Virginia E.; Peters, C. P.

    2012-01-01

    Most pharmaceuticals are metabolized by the liver. Clinically-used medication doses are given with normal liver function in mind. A drug overdose can result if the liver is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism we want to understand the effects of spaceflight on the enzymes of the liver.

  8. Severe hepatic encephalopathy in a patient with liver cirrhosis after administration of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker combination therapy: a case report

    Directory of Open Access Journals (Sweden)

    Podda Mauro

    2010-05-01

    Full Text Available Abstract Introduction A combination therapy of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers has been used to control proteinuria, following initial demonstration of its efficacy. However, recently concerns about the safety of this therapy have emerged, prompting several authors to urge for caution in its use. In the following case report, we describe the occurrence of a serious and unexpected adverse drug reaction after administration of a combination of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers to a patient with nephrotic syndrome and liver cirrhosis with severe portal hypertension. Case presentation We administered this combination therapy to a 40-year-old Caucasian man with liver cirrhosis in our Hepatology Clinic, given the concomitant presence of glomerulopathy associated with severe proteinuria. While the administration of one single drug appeared to be well-tolerated, our patient developed severe acute encephalopathy after the addition of the second one. Discontinuation of the therapy led to the disappearance of the side-effect. A tentative rechallenge with the same drug combination led to a second episode of acute severe encephalopathy. Conclusion We speculate that this adverse reaction may be directly related to the effect of angiotensin II on the excretion of blood ammonia. Therefore, we suggest that patients with liver cirrhosis and portal hypertension are at risk of developing clinically relevant encephalopathy when angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker combination therapy is administered, thus indicating the need for a careful clinical follow-up. In addition, the incidence of this serious side-effect should be rigorously evaluated in all patients with liver cirrhosis administered with this common treatment combination.

  9. Effect of x-irradiation on the activity of the key enzymes of the synthesis and degradation of heme in rat liver

    International Nuclear Information System (INIS)

    Deev, L.I.; Topchishvili, G.I.; Akhalaya, M.Ya.; Platonov, A.G.

    1985-01-01

    For Wistar rat males the effect of X radiation on the activity of delta-aminolevuminatesynthase and chemoxygenase - the rate of limiting enzymes of synthesis and catabolism of heme, as well as the level of ''free'' (non-utilized) heme in the rat liver are studied. The animals were irradiated using the X-ray device with the dose rate 0.5 Gy/min. X irradiation in the minimum lethal dose (7 Gy) caused evident changes in the activity of delta-aminolevuminatesynthase and chemoxygenase in the rat liver. Already one day after irradiation a noticeable decrease in the activity of delta-aminoleviminatesynthase (up to 81% of the normal one) was observed, and the maximum decrease took place on the third day (49% of the norm). On the 5-7-th day partial normalization of the activity of delta-aminoleviminatesynthase occurred. The chemoxygenase activity at the initial period after irradiation (1 day after) increased, after that (on the 5-7-th day), the phase of more than twofold and prolonged increase in the enzyme activity followed. Irradiation of animals by the dose of 5 Gy did not induce reliable changes in the activity of chemoxygenase and caused a considerably lower decrease in the activity of delta-aminolevunatesynthase. The observed suppression of synthesis and increase in heme catabolism do not result in the decrease in the level of ''free'' heme in the liver of irradiated animals. The conclusion is made on the presence of considerable violations of heme metabolism in the liver of irradiated animals, however, there is no final answer to the question on the role of detected effects in the decrease of microsomal level of cytochrome R-450

  10. Tissue specific distribution of pyrimidine deoxynucleoside salvage enzymes shed light on the mechanism of mitochondrial DNA depletion.

    Science.gov (United States)

    Wang, L; Eriksson, S

    2010-06-01

    Deficiency in thymidine kinase 2 (TK2) activity due to genetic alterations caused tissue specific mitochondrial DNA (mtDNA) depletion syndrome with symptoms resembling these of AIDS patients treated with nucleoside analogues. Mechanisms behind this mitochondrial effects is still not well understood. With rat as a model we isolated mitochondrial and cytosolic fractions from major organs and studied enzymes involved in thymidine (dT) and deoxycytidine (dC) phosphorylation by using ionic exchange column chromatography. A cytosolic form of TK2 was identified in all tested tissues in addition to mitochondrial TK2. TK1 was detected in liver and spleen cytosolic extracts while dCK was found in liver, spleen and lung cytosolic extracts. Thus, the nature of dT and dC salvage enzymes in each tissue type was determined. In most tissues TK2 is the only salvage enzyme present except liver and spleen. These results may help to explain the mechanisms of mitochondrial toxicity of antiviral nucleoside analogues and mtDNA depletion caused by TK2 deficiency.

  11. Obese mice fed a diet supplemented with enzyme-treated wheat bran display marked shifts in the liver metabolome concurrent with altered gut bacteria

    Science.gov (United States)

    Enzyme-treated wheat bran (ETWB) is a fermentable dietary fiber previously shown to decrease liver triglycerides and modify the gut microbiome in mice. It is not clear which mechanisms explain how ETWB feeding impacts hepatic metabolism, but factors (i.e., metabolites) associated with specific micro...

  12. Acute Liver Toxicity due to Efavirenz/Emtricitabine/Tenofovir

    Directory of Open Access Journals (Sweden)

    Rashmee Patil

    2015-01-01

    Full Text Available The fixed-dose combination of Efavirenz/Emtricitabine/Tenofovir is a first-line agent for the treatment of HIV; however few cases have reported hepatotoxicity associated with the drug. We report a case of Efavirenz/Emtricitabine/Tenofovir-associated hepatotoxicity presenting mainly with hepatocellular injury characterized by extremely elevated aminotransferase levels, which resolved without acute liver failure or need for liver transplant referral.

  13. Dose of Phenobarbital and Age of Treatment at Early Life are Two Key Factors for the Persistent Induction of Cytochrome P450 Enzymes in Adult Mouse Liver.

    Science.gov (United States)

    Tien, Yun-Chen; Liu, Ke; Pope, Chad; Wang, Pengcheng; Ma, Xiaochao; Zhong, Xiao-bo

    2015-12-01

    Drug treatment of neonates and infants and its long-term consequences on drug responses have emerged in recent years as a major challenge for health care professionals. In the current study, we use phenobarbital as a model drug and mouse as an in vivo model to demonstrate that the dose of phenobarbital and age of treatment are two key factors for the persistent induction of gene expression and consequential increases of enzyme activities of Cyp2b, Cyp2c, and Cyp3a in adult livers. We show that phenobarbital treatment at early life of day 5 after birth with a low dose (phenobarbital treatment with a high dose (>200 mg/kg) significantly increases expression and enzyme activities of these P450s in adult liver. We also demonstrate that phenobarbital treatment before day 10 after birth, but not at later ages, significantly increases mRNAs, proteins, and enzyme activities of the tested P450s. Such persistent induction of P450 gene expression and enzyme activities in adult livers by phenobarbital treatment only occurs within a sensitive age window early in life. The persistent induction in gene expression and enzyme activities is higher in female mice than in male mice for Cyp2b10 but not for Cyp2c29 and Cyp3a11. These results will stimulate studies to evaluate the long-term impacts of drug treatment with different doses at neonatal and infant ages on drug metabolism, therapeutic efficacy, and drug-induced toxicity throughout the rest of life. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  14. Studies on estradiol-2/4-hydroxylase activity in rat brain and liver

    International Nuclear Information System (INIS)

    Theron, C.N.

    1985-03-01

    A sensitive and specific radio-enzymatic assay was used to study estradiol-2/4-hydroxylase activity in rat liver microsomes and in microsomes obtained from 6 discrete brain areas of the rat. Kinetic parameters were determined for these enzyme activities. The effects of different P-450 inhibitors on estradiol-2/4-hydroxylase activity in brain and liver microsomes were also studied. In both organs these enzyme activities were found to be located mainly in the microsomal fraction and were inhibited by the 3 P-450 inhibitors tested. The hepatic estradiol-2/4-hydroxylase activity in adult male rats was significantly higher than that of females, but the enzyme activity in the brain did not exhibit a similar sex difference. Furthermore, estradiol-2/4-hydroxylase activity in rat liver was strongly induced by phenobarbitone treatment, but not in the brain. The phenobarbitone-induced activity in male and female rats exhibited significant kinetic differences. In female rats sexual maturation was associated with significant changes in the apparent Km of estradiol-2/4-hydroxylases in the liver and hypothalamus. Evidence was found that the in vitro estradiol-2/4-hydroxylase activity in rat brain and liver is due to more than one form of microsomal P-450. Kinetic studies showed important differences between the estradiol-2/4-hydroxylase activities in the hippocampus and hypothalamus. Significant differences in estradiol-2/4-hydroxylase activities were observed in the 6 brain areas studied, with the hippocampus showing the highest, and the hypothalamus the lowest activity at all developmental stages in both male and female rats

  15. diagnosing multiple opportunistic infections: the value of a liver ...

    African Journals Online (AJOL)

    THE SOUTHERN AFRICAN JOURNAL OF HIV MEDICINE Spring 2008. 51 ... standard TB therapy. The initial HIV diagnosis ... with elevated transaminases and canalicular enzymes, ... pattern of liver enzyme abnormalities was unchanged. Of note ... This case illustrates the diagnostic value of liver biopsy in our local patient.

  16. Effect of Phenanthrene on the Tissue Structure of Liver and Aminotransferase Enzymes in Yellowfin Seabream (Acanthopagrus latus

    Directory of Open Access Journals (Sweden)

    Mehrnaz Shirmohammadi*

    2017-06-01

    Full Text Available Background: Polycyclic aromatic hydrocarbons (PAHs such as phenanthrene (Phe represent one of the most abundant forms of organic pollutants. The aim of this study was to assess changes in plasma levels of aminotransferase enzymes, total protein and liver tissue as biomarkers of yellowfin seabream (Acanthopagrus latus exposed to Phe for 14 d. Methods: The research was carried out in January 2016 at Khorramshahr University of Marine Sciences and Technology, Khorramshahr, Iran. Some 72 fish were injected with 2, 20, 40 and 70 mg/kg of Phe. Then tissue and blood samples were obtained at 1, 4, 7 and 14 d after injection. Results: Exposure of fish to Phe resulted in a significant increase of alanine aminotransferase (ALT, aspartate aminotransferase (AST and decrease of total protein after 7 d of the experiment (P<0.05. The main histopathological alteration was showed in different sampling days including nucleus margination, hypertrophy, vacuolation, melanomacrophages aggregates, sinusoid dilation, degeneration and picnotic nucleus. Degree of tissue change (DTC of liver was recorded in the Phe-exposed fish from normal range to moderate changes. Conclusion: The studied biomarkers such as changes in concentrations of ALT, AST and total protein as well as tissue damages in liver may be served as beneficial biomarker to assess Phe toxicity in yellowfin seabream.

  17. Daily chocolate consumption is inversely associated with insulin resistance and liver enzymes in the Observation of Cardiovascular Risk Factors in Luxembourg study.

    Science.gov (United States)

    Alkerwi, Ala'a; Sauvageot, Nicolas; Crichton, Georgina E; Elias, Merrill F; Stranges, Saverio

    2016-05-01

    This study examined the association of chocolate consumption with insulin resistance and serum liver enzymes in a national sample of adults in Luxembourg. A random sample of 1153 individuals, aged 18-69 years, was recruited to participate in the cross-sectional Observation of Cardiovascular Risk Factors in Luxembourg study. Chocolate consumption (g/d) was obtained from a semi-quantitative FFQ. Blood glucose and insulin levels were used for the homoeostasis model assessment of insulin resistance (HOMA-IR). Hepatic biomarkers such as serum γ-glutamyl-transpeptidase (γ-GT), serum aspartate transaminase and serum alanine transaminase (ALT) (mg/l) were assessed using standard laboratory assays. Chocolate consumers (81·8 %) were more likely to be younger, physically active, affluent people with higher education levels and fewer chronic co-morbidities. After excluding subjects taking antidiabetic medications, higher chocolate consumption was associated with lower HOMA-IR (β=-0·16, P=0·004), serum insulin levels (β=-0·16, P=0·003) and γ-GT (β=-0·12, P=0·009) and ALT (β=-0·09, P=0·004), after adjustment for age, sex, education, lifestyle and dietary confounding factors, including intakes of fruits and vegetables, alcohol, polyphenol-rich coffee and tea. This study reports an independent inverse relationship between daily chocolate consumption and levels of insulin, HOMA-IR and liver enzymes in adults, suggesting that chocolate consumption may improve liver enzymes and protect against insulin resistance, a well-established risk factor for cardiometabolic disorders. Further observational prospective research and well-designed randomised-controlled studies are needed to confirm this cross-sectional relationship and to comprehend the role and mechanisms that different types of chocolate may play in insulin resistance and cardiometabolic disorders.

  18. Method of preparing highly active and thermostable preparations of liver uridin-kinase usable for enzymic synthesis of radioactive nucleoside-5'-phosphates

    International Nuclear Information System (INIS)

    Cihak, A.; Vesely, J.

    1975-01-01

    A method is described of preparing a high-activity uridine kinase for the enzymic synthesis of radioactive nucleoside-5m-phosphates of the pyrimidine series. The preparation is separated from male rat liver after intraperitoneal application of 5'-azacytidine. Examples are given showing detailed procedures for the conversion of uridine and 6-azauridine to the corresponding 5'-phosphates. (L.K.)

  19. 21 CFR 184.1034 - Catalase (bovine liver).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Catalase (bovine liver). 184.1034 Section 184.1034... Listing of Specific Substances Affirmed as GRAS § 184.1034 Catalase (bovine liver). (a) Catalase (bovine liver) (CAS Reg. No. 81457-95-6) is an enzyme preparation obtained from extracts of bovine liver. It is...

  20. ASSOCIATION OF CARDIORESPIRATORY FITNESS WITH ELEVATED HEPATIC ENZYME AND LIVER FAT IN JAPANESE PATIENTS WITH IMPAIRED GLUCOSE TOLERANCE AND TYPE 2 DIABETES MELLITUS

    Directory of Open Access Journals (Sweden)

    Mayumi Nagano

    2010-09-01

    Full Text Available No study has so far determined whether a favorable level of cardiorespiratory fitness (CF contributes to a reduced risk of elevated hepatic enzymes and a high degree of liver fat in patients having various metabolic risks. This study investigated the association between the maximal oxygen uptake (VO2 max and the prevalence of elevated liver enzymes and high liver fat, while considering such factors as abdominal obesity, hyperinsulinemia and the other metabolic risks. The study enrolled newly diagnosed Japanese patients (n = 84; 52 males and 32 females; aged 25-69 years with impaired glucose tolerance (IGT and type 2 diabetes mellitus (Type2DM who did not receive any intervention or pharmacological therapy. The subjects were divided into 3 groups according to the distribution of the VO2max for each sex. The odds ratios (ORs for the prevalence of elevated aspartate and alanine aminotransferase (AST and ALT and high degree of liver fat adjusted for age, sex, disease type, daily ethanol intake, and current smoking were significantly lower in the moderate- and high CF groups in comparison to the low CF group. In addition, a significant OR for AST was maintained in the moderate and high CF group after adjusting for abdominal obesity and/or hyperinsulinemia. The significant ORs for the prevalence of elevated ALT and a high degree of liver fat were attenuated after adjusting for abdominal obesity and/or hyperinsulinemia. No significant OR for the prevalence of elevated gamma-glutamyl transferase (GGT was recognized in all logistic models. These results indicated that CF was negatively and independently associated with the prevalence of elevated AST even in Japanese diabetic patients having various metabolic risks. It was concluded that the AST level might be useful as a simple marker reflecting physical inactivity in such subjects

  1. Redox regulation of antioxidant enzymes: post-translational modulation of catalase and glutathione peroxidase activity by resveratrol in diabetic rat liver.

    Science.gov (United States)

    Sadi, Gökhan; Bozan, Davut; Yildiz, Huseyin Bekir

    2014-08-01

    Resveratrol is a strong antioxidant that exhibits blood glucose-lowering effects, which might contribute to its usefulness in preventing complications associated with diabetes. The present study aimed to investigate resveratrol effects on catalase (CAT) and glutathione peroxidase (GPx) gene and protein expression, their phosphorylation states and activities in rat liver of STZ-induced diabetes. Diabetes increased the levels of total protein phosphorylation and p-CAT, while mRNA expression, protein levels, and activity were reduced. Although diabetes induced transcriptional repression over GPx, it did not affect the protein levels and activity. When resveratrol was administered to diabetic rats, an increase in activity was associated with an increase in p-GPx levels. Decrease in Sirtuin1 (SIRT1) and nuclear factor erythroid 2-related factor (Nrf2) and increase in nuclear factor kappa B (NFκB) gene expression in diabetes were associated with a decrease in CAT and GPx mRNA expression. A possible compensatory mechanism for reduced gene expression of antioxidant enzymes is proved to be nuclear translocation of redox-sensitive Nrf2 and NFκB in diabetes which is confirmed by the increase in nuclear and decrease in cytoplasmic protein levels of Nrf2 and NFκB. Taken together, these findings revealed that an increase in the oxidized state in diabetes intricately modified the cellular phosphorylation status and regulation of antioxidant enzymes. Gene regulation of antioxidant enzymes was accompanied by nuclear translocation of Nrf2 and NFκB. Resveratrol administration also activated a coordinated cytoprotective response against diabetes-induced changes in liver tissues.

  2. Liver BCATm transgenic mouse model reveals the important role of the liver in maintaining BCAA homeostasis.

    Science.gov (United States)

    Ananieva, Elitsa A; Van Horn, Cynthia G; Jones, Meghan R; Hutson, Susan M

    2017-02-01

    Unlike other amino acids, the branched-chain amino acids (BCAAs) largely bypass first-pass liver degradation due to a lack of hepatocyte expression of the mitochondrial branched-chain aminotransferase (BCATm). This sets up interorgan shuttling of BCAAs and liver-skeletal muscle cooperation in BCAA catabolism. To explore whether complete liver catabolism of BCAAs may impact BCAA shuttling in peripheral tissues, the BCATm gene was stably introduced into mouse liver. Two transgenic mouse lines with low and high hepatocyte expression of the BCATm transgene (LivTg-LE and LivTg-HE) were created and used to measure liver and plasma amino acid concentrations and determine whether the first two BCAA enzymatic steps in liver, skeletal muscle, heart and kidney were impacted. Expression of the hepatic BCATm transgene lowered the concentrations of hepatic BCAAs while enhancing the concentrations of some nonessential amino acids. Extrahepatic BCAA metabolic enzymes and plasma amino acids were largely unaffected, and no growth rate or body composition differences were observed in the transgenic animals as compared to wild-type mice. Feeding the transgenic animals a high-fat diet did not reverse the effect of the BCATm transgene on the hepatic BCAA catabolism, nor did the high-fat diet cause elevation in plasma BCAAs. However, the high-fat-diet-fed BCATm transgenic animals experienced attenuation in the mammalian target of rapamycin (mTOR) pathway in the liver and had impaired blood glucose tolerance. These results suggest that complete liver BCAA metabolism influences the regulation of glucose utilization during diet-induced obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Constipation due to Liver Disorder in Iranian Traditional Medicine`s Viewpoint

    Directory of Open Access Journals (Sweden)

    R Choopani

    2014-04-01

    Full Text Available Introduction: Constipation is one of the most common pediatric disorders.In many cases, there is no anatomic endocrineor metabolic cause in explanation of chronic constipation.More than 85% of them called functional or idiopathic.Constipation is one of the serious disease in Iranian Traditional Medicine. Besides the problem it causes, chronic constipation can be the origin of many disease. That is why, ithas been called Mother of disease.The purpose of this study is to investigate the Constipation in children and the role of other organs such as the liver by view of Iranian Traditional Medicine   Materials and Method: This study is a review through Iranian traditional medicine references. At first, all the main available traditional books were reviewed. All the data about therapies of vaginal discharge in ITM were collected then classified.   Results: In traditional medicine different reasons have been mentioned for constipation especially for childrenwhich most of them are similar to etiology in Modern Medicine.Constipation due to liver disorder is one of the causes of constipation.In Iranian Traditional medicine` viewpoint, one of the mechanism for excretion is existence of secreted bile in intestine.If by any reason,measure or quality of its which secreted in intestine through bile changes or if intestinal mucous secretion becomes barrier for absorbing the food,it will caused disorder in excretion and finally will lead to constipation.Well known Iranian Traditional Medicine scientists, has mentioned all reasons for liver disorders and changing quality& quantity of secreted bile .he has mentioned the solutions as well.   Conclusion: It is hoped that by paying attention to constipation and with advanced clinical research we will be able to explain idiopathic constipation and prepare new ways of treatments for constipation. New researches have approved the effectiveness of these foods and drugs for treating the constipation.   Keywords

  4. Acute liver failure due to natural killer-like T-cell leukemia/lymphoma: A case report and review of the Literature

    Institute of Scientific and Technical Information of China (English)

    Evan S Dellon; Shannon R Morris; Wozhan Tang; Cherie H Dunphy; Mark W Russo

    2006-01-01

    Acute liver failure (ALF) is a medical emergency requiring immediate evaluation for liver transplantation. We describe an unusual case of a patient who presented with ascites, jaundice, and encephalopathy and was found to have ALF due to natural killer (NK)-like T cell leukemia/lymphoma. The key immunophenotype was CD2+, CD3+, CD7+, CD56+. This diagnosis, which was based on findings in the peripheral blood and ascitic fluid, was confirmed with liver biopsy, and was a contraindication to liver transplantation. A review of the literature shows that hematologic malignancies are an uncommon cause of fulminant hepatic failure, and that NK-like T-cell leukemia/lymphoma is a relatively recently recognized entity which is characteristically CD3+ and CD56+. This case demonstrates that liver biopsy is essential in diagnosing unusual causes of acute liver failure, and that infiltration of the liver with NK-like T-cell lymphoma/leukemia can cause acute liver failure.

  5. Liver involvement in Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    Wong, Adelaine; Ortiz-Neira, Clara L.; Abou Reslan, Walid; Kaura, Deepak; Sharon, Raphael; Anderson, Ronald; Pinto-Rojas, Alfredo

    2006-01-01

    Liver involvement in Langerhans cell histiocytosis (LCH) typically presents with hepatomegaly and other signs of liver dysfunction. We present an 11-month-old child having only minimally elevated liver enzymes as an indication of liver involvement. Using sonography as the initial diagnostic tool followed by MRI, LCH of the liver was revealed. A review of sonographic, CT, MRI and MR cholangiopancreatography findings in liver LCH is presented. We recommend that physicians consider sonography and MRI screening for liver involvement in patients with newly diagnosed LCH, as periportal involvement may be present with little or no liver function abnormality present, as in this patient. (orig.)

  6. [Current seroprevalence, vaccination and predictive value of liver enzymes for hepatitis B among refugees in Germany].

    Science.gov (United States)

    Hampel, Annika; Solbach, Philipp; Cornberg, Markus; Schmidt, Reinhold E; Behrens, Georg M N; Jablonka, Alexandra

    2016-05-01

    Currently only vague estimates exist for the seroprevalence and vaccination status for viral hepatitis B (HBV) in refugees arriving in Germany during the current refugee crisis. To assess the prevalence of hepatitis B in refugees arriving in northern Germany in 2015. In a cross-sectional study in 793 patients from all age groups tests for serological markers of hepatitis B virus infection (HBsAg, anti-HBc) and liver enzymes (ALT, AST, bilirubin, γGT, alkaline phosphatase) were performed in August 2015 at six reception centers in northern Germany. In 258 patients anti-HBs antibodies were assessed additionally. Of the tested refugees, 76.7 % were male, the median age was 28.8 ± 11.4 years, and 7.8 % were children under the age of 18. The overall prevalence of HBsAg and total anti-HBc was 2.3 % and 14.0 % respectively (2.5 % and 14.5 % in men; 1.2 % and 13.5 % in women). Prevalence was highest in 35 to 49-year-old patients for HBsAg (3.1 %) and for refugees over 50 years for anti-HBc (38 %). No immunity to Hepatitis B was found in 62 %, 18.6 % had been vaccinated against Hepatitis B, while 50 % of children aged up to 15 years (n = 12) had been vaccinated. Positive predictive values of elevated AST and ALT for detection of HBsAg was 0 and 0.016, respectively. Only two patients with a positive HBsAg had elevated transaminases. This study showed a high prevalence of HBsAg in a German refugee sample in comparison to the general German population. Liver enzymes are not an appropriate tool for screening for hepatitis B virus infection.

  7. Moro orange juice prevents fatty liver in mice.

    Science.gov (United States)

    Salamone, Federico; Li Volti, Giovanni; Titta, Lucilla; Puzzo, Lidia; Barbagallo, Ignazio; La Delia, Francesco; Zelber-Sagi, Shira; Malaguarnera, Michele; Pelicci, Pier Giuseppe; Giorgio, Marco; Galvano, Fabio

    2012-08-07

    To establish if the juice of Moro, an anthocyanin-rich orange, may improve liver damage in mice with diet-induced obesity. Eight-week-old mice were fed a high-fat diet (HFD) and were administrated water or Moro juice for 12 wk. Liver morphology, gene expression of lipid transcription factors, and metabolic enzymes were assessed. Mice fed HFD displayed increased body weight, insulin resistance and dyslipidemia. Moro juice administration limited body weight gain, enhanced insulin sensitivity, and decreased serum triglycerides and total cholesterol. Mice fed HFD showed liver steatosis associated with ballooning. Dietary Moro juice markedly improved liver steatosis by inducing the expression of peroxisome proliferator-activated receptor-α and its target gene acylCoA-oxidase, a key enzyme of lipid oxidation. Consistently, Moro juice consumption suppressed the expression of liver X receptor-α and its target gene fatty acid synthase, and restored liver glycerol-3-phosphate acyltransferase 1 activity. Moro juice counteracts liver steatogenesis in mice with diet-induced obesity and thus may represent a promising dietary option for the prevention of fatty liver.

  8. Liver Melanomacrophages and Gluthation S-Transferase Activity in Leptodactylus chaquensis (ANURA, LEPTODACTYLIDAE as Biomarkers of Oxidative Stress Due to Chlorpyrifos Exposition

    Directory of Open Access Journals (Sweden)

    Ivan Huespe

    2017-05-01

    Full Text Available We quantified and compared the hepatic melanomacrophage (MM and glutathione S-transferase (GST enzyme activity (two oxidative stress biomarkers in the liver of Leptodatylus chaquensis adults (Anura, Leptodactylidae collected in a rice field (CA in San Javier department, Santa Fe (Argentina, seven days after the application of chlorpyrifos and in a reference site (SR. The histological analysis revealed a significant amount (p = 0.028 and area occupied by MM (p = 0.017 in livers of CA compared to SR. Furthermore, a significant inhibition of GST activity was recorded in the CA frogs compared to the SR (p = 0.030. The histopathological and enzymatic effects provide evidences of ecotoxicological risk for anurans in rice field with CPF application.

  9. The effect of apple (Malus Domestica juice on the damage of mice liver cells due to paracetamol treatment

    Directory of Open Access Journals (Sweden)

    Anthony Hartanto

    2009-07-01

    Full Text Available The liver is an important organ for body metabolism process. Liver disease is one of serious health problems in developing countries including Indonesia. Liver damage is caused by viral infection, toxic agent exposure (medications, alcohol, hormonal disturbance, neoplasm and autoimmune diseases. The use of high dose paracetamol to reduce pain also leads to liver damage. Apple (Malus domestica juice is a natural anti oxidant agent. This laboratory experimental study was performed to discover the effect of giving apple juice on damaged cell regeneration due to the use of paracetamol. The study was performed in 21 male mice from Swiss-Webster strain that were divided into group I, II, and III. Group, I served as control while group II received 1 mg/ml paracetamol dose for 5 days and Group III received 1 mg/ml paracetamol for 5 days and 1 ml of apple juice on the 5th to 10th day. The observation of the mice liver cells was conducted using a light microscope with 400x magnification to get the number of necrotic liver cells per view field. The results of this study showed a difference in the number of necrotic liver cells between Group II and III. ANOVA statistical test ( = 0.05 concluded that apple juice significantly helps regeneration process in damaged liver cells caused by paracetamol.

  10. PROTECTIVE EFFECT OF MORINGA PEREGRINA LEAVES EXTRACT ON ACETAMINOPHEN -INDUCED LIVER TOXICITY IN ALBINO RATS.

    Science.gov (United States)

    Azim, Samy Abdelfatah Abdel; Abdelrahem, Mohamed Taha; Said, Mostafa Mohamed; Khattab, Alshaimaa

    2017-01-01

    Acetaminophen is a common antipyretic drug but at overdose can cause severe hepatotoxicity that may further develop into liver failure and hepatic centrilobular necrosis in experimental animals and humans. This study was undertaken to assess the ameliorative role of Moringa peregrina leaves extract against acetaminophen toxicity in rats. Induction of hepatotoxicity was done by chronic oral administration of acetaminophen (750 mg/kg bwt) for 4 weeks. To study the possible hepatoprotective effect, Moringa peregrina leaves extract (200 mg/kg bwt) or Silymarin (50 mg/kg bwt) was administered orally, for 4 weeks, along with acetaminophen. acetaminophen significantly increased serum liver enzymes and caused oxidative stress, evidenced by significantly increased tissue malondialdehyde, glutathione peroxidase, hepatic DNA fragmentation, and significant decrease of glutathione and antioxidant enzymes in liver, blood and brain. On the other hand, administration of Moringa peregrina leaves extract reversed acetaminophen-related toxic effects through: powerful malondialdehyde suppression, glutathione peroxidase normalization and stimulation of the cellular antioxidants synthesis represented by significant increase of glutathione, catalase and superoxide dismutase in liver, blood and brain, besides, DNA fragmentation was significantly decreased in the liver tissue. acetaminophen induced oxidative damage can be improved by Moringa peregrina leaves extract-treatment, due to its antioxidant potential.

  11. Associations of Insulin Resistance and Glycemia With Liver Enzymes in Hispanic/Latino Youths: Results From the Hispanic Community Children's Health Study/Study of Latino Youth (SOL Youth).

    Science.gov (United States)

    Parrinello, Christina M; Rudolph, Bryan J; Lazo, Mariana; Gallo, Linda C; Thyagarajan, Bharat; Cotler, Scott J; Qi, Qibin; Seeherunvong, Tossaporn; Vidot, Denise C; Strickler, Howard D; Kaplan, Robert C; Isasi, Carmen R

    2017-11-03

    Associations of insulin resistance and hyperglycemia with a panel of liver enzymes have not been well studied in a young, heterogenous Hispanic/Latino population. We aimed to assess the associations of insulin resistance and glycemia with nonalcoholic fatty liver disease (NAFLD), as measured by liver enzymes and the pediatric NAFLD fibrosis index (PNFI), and whether these associations are modified by body mass index and mediated by inflammation or endothelial dysfunction. We conducted a cross-sectional study of 1317 boys and girls aged 8 to 16 years from the Hispanic Community Children's Health Study/Study of Latino Youth. We used Poisson regression to assess the associations of fasting glucose, hemoglobin A1c, and homeostasis model assessment of insulin resistance (HOMA-IR) with elevated alanine aminotransferase (ALT) (>25 U/L in boys, >22 U/L in girls), aspartate aminotransferase (AST) (≥37 U/L), gamma-glutamyl transpeptidase (GGT) (≥17 U/L), and PNFI (≥9; a function of age, waist circumference, and triglyceride level). HOMA-IR was associated with elevated ALT, AST, GGT, and PNFI [prevalence ratios (95% confidence intervals) for each 1-unit increase in the natural log of HOMA-IR: 1.99 (1.40-2.81), 2.15 (1.12-4.12), 1.70 (1.26-2.30), and 1.98 (1.43-2.74), respectively]. Associations were observed in overweight/obese children, but not in normal weight children (P-interaction=0.04 for AST and P-interaction=0.07 for GGT). After further adjustment for adiponectin, high-sensitivity C-reactive protein, e-selectin, and PAI-1, associations of HOMA-IR with liver enzymes and PNFI were attenuated, but remained statistically significant for AST and PNFI. Insulin resistance was associated with NAFLD in overweight/obese Hispanic/Latino youth, and this association may be partially mediated by inflammation and endothelial dysfunction.

  12. Invasive candidiasis due to Candida norvegensis in a liver transplant patient: case report and literature review

    Directory of Open Access Journals (Sweden)

    Maria Musso

    2014-06-01

    Full Text Available Candida norvegensis is an emerging fluconazole-resistant pathogen isolated in most cases from skin and mucous membranes of immunocompromized patients. Documented invasive candidiasis (IC due to C. norvegensis has been rarely reported, thus the clinical features of patients at risk for this pathogen are poorly defined. We report a liver transplant patient who developed IC due to C. norvegensis and review other cases of C. norvegensis IC published in the literature.

  13. LIVER FUNCTION CHANGES IN PATIENTS WITH SPONDYLOARTHRITIS TAKING NONSTEROIDAL ANTI-INFLAMMATORY DRUGS OVER A LONG PERIOD: RESULTS OF A 10-YEAR PROGRESS PROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    A. P. Rebrov

    2016-01-01

    Full Text Available Objective: to assess liver function changes in patients with spondyloarthritis (SpA taking NSAIDs regularly over a long period.Patients and methods. The data obtained during a 10-year PROGRESS prospective single-center cohort study of functional status, activity, and comorbidity (including gastrointestinal tract diseases in patients with SpA were analyzed. The data of 363 SpA patients receiving NSAIDs regularly over a long period and followed up for 10 years were also explored. The changes that had occurred over a decade in the liver enzyme levels, the number of discontinued NSAID treatments because of a persistent increase in liver enzyme levels, and the number of prescriptions of hepatoprotective agents were analyzed.Results. For 10 years, 18 patients with SpA discontinued their NSAID intake due to elevated liver enzyme levels (≥3 times greater than the reference value; during that time, the same increase in enzyme levels was observed in 2 healthy individuals (χ2 =1.39; p=0.2. In the patients with SpA as compared to the healthy individuals, the relative risk of abnormal liver function was 1.19 (95% CI, 1.009–1.405; odds ratio was 2.9 (95% CI, 0.65–12.95. There was no increased risk for discontinuation of some NSAIDs, including nimesulide (χ2 =0.03, p=0.85, the frequency of using hepatoprotective drugs was proved to be highest for diclofenac sodium, ibuprofen, nimesulide, and ketoprofen.Conclusion. The regular long-term (as long as 10 years use of NSAIDs to treat SpA is associated with treatment discontinuation because of elevated enzyme levels in every 10 patients. The maximum rate of discontinuation of NSAIDs due to a persistent increase in liver enzyme levels is observed 6–8 years after their regular use, so long-term NSAID therapy requires continuous monitoring of hepatic safety. The longterm intake of nimesulide, as compared with other NSAIDs, is shown to be unassociated with the higher rate of its discontinuation because of

  14. Quantitative Characterization of Major Hepatic UDP-Glucuronosyltransferase Enzymes in Human Liver Microsomes: Comparison of Two Proteomic Methods and Correlation with Catalytic Activity.

    Science.gov (United States)

    Achour, Brahim; Dantonio, Alyssa; Niosi, Mark; Novak, Jonathan J; Fallon, John K; Barber, Jill; Smith, Philip C; Rostami-Hodjegan, Amin; Goosen, Theunis C

    2017-10-01

    Quantitative characterization of UDP-glucuronosyltransferase (UGT) enzymes is valuable in glucuronidation reaction phenotyping, predicting metabolic clearance and drug-drug interactions using extrapolation exercises based on pharmacokinetic modeling. Different quantitative proteomic workflows have been employed to quantify UGT enzymes in various systems, with reports indicating large variability in expression, which cannot be explained by interindividual variability alone. To evaluate the effect of methodological differences on end-point UGT abundance quantification, eight UGT enzymes were quantified in 24 matched liver microsomal samples by two laboratories using stable isotope-labeled (SIL) peptides or quantitative concatemer (QconCAT) standard, and measurements were assessed against catalytic activity in seven enzymes ( n = 59). There was little agreement between individual abundance levels reported by the two methods; only UGT1A1 showed strong correlation [Spearman rank order correlation (Rs) = 0.73, P quantitative proteomic data should be validated against catalytic activity whenever possible. In addition, metabolic reaction phenotyping exercises should consider spurious abundance-activity correlations to avoid misleading conclusions. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  15. HBK-14 and HBK-15 Do Not Influence Blood Pressure, Lipid Profile, Glucose Level, or Liver Enzymes Activity after Chronic Treatment in Rats.

    Science.gov (United States)

    Pytka, Karolina; Głuch-Lutwin, Monika; Knutelska, Joanna; Jakubczyk, Magdalena; Waszkielewicz, Anna; Kotańska, Magdalena

    2016-01-01

    Older and even new antidepressants cause adverse effects, such as orthostatic hypotension, hyper- or hypoglycemia, liver injury or lipid disorders. In our previous experiments we showed significant antidepressant- and anxiolytic-like activities of dual 5-HT1A and 5-HT7 antagonists with α1-adrenolitic properties i.e. 1-[(2,6-dimethylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-14) and 1-[(2-chloro-6-methylphenoxy)ethoxyethyl]-4-(2-methoxyphenyl)piperazine hydrochloride (HBK-15). Here, we evaluated the influence of chronic administration of HBK-14 and HBK-15 on blood pressure (non-invasive blood pressure measurement system for rodents), lipid profile (total cholesterol, low density lipoproteins-LDL, high density lipoproteins-HDL, triglycerides), glucose level, and liver enzymes activity (aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase). We determined potential antihistaminic (isolated guinea pig ileum) and antioxidant properties (ferric reducing ability of plasma-FRAP, non-protein thiols-NPSH, stable free radical diphenylpicrylhydrazyl-DPPH) cytotoxicity. Our experiments revealed that HBK-14 and HBK-15 did not influence blood pressure, lipid profile, glucose level or liver enzymes activity in rats after 2-week treatment. We also showed that none of the compounds possessed antioxidant or cytotoxic properties at antidepressant- and anxiolytic-like doses. HBK-14 and HBK-15 very weakly blocked H1 receptors in guinea pig ileum. Positive results of our preliminary experiments on the safety of HBK-14 and HBK-15 encourage further studies concerning their effectiveness in the treatment of depression and/or anxiety disorders.

  16. HBK-14 and HBK-15 Do Not Influence Blood Pressure, Lipid Profile, Glucose Level, or Liver Enzymes Activity after Chronic Treatment in Rats.

    Directory of Open Access Journals (Sweden)

    Karolina Pytka

    Full Text Available Older and even new antidepressants cause adverse effects, such as orthostatic hypotension, hyper- or hypoglycemia, liver injury or lipid disorders. In our previous experiments we showed significant antidepressant- and anxiolytic-like activities of dual 5-HT1A and 5-HT7 antagonists with α1-adrenolitic properties i.e. 1-[(2,6-dimethylphenoxyethoxyethyl]-4-(2-methoxyphenylpiperazine hydrochloride (HBK-14 and 1-[(2-chloro-6-methylphenoxyethoxyethyl]-4-(2-methoxyphenylpiperazine hydrochloride (HBK-15. Here, we evaluated the influence of chronic administration of HBK-14 and HBK-15 on blood pressure (non-invasive blood pressure measurement system for rodents, lipid profile (total cholesterol, low density lipoproteins-LDL, high density lipoproteins-HDL, triglycerides, glucose level, and liver enzymes activity (aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase. We determined potential antihistaminic (isolated guinea pig ileum and antioxidant properties (ferric reducing ability of plasma-FRAP, non-protein thiols-NPSH, stable free radical diphenylpicrylhydrazyl-DPPH cytotoxicity. Our experiments revealed that HBK-14 and HBK-15 did not influence blood pressure, lipid profile, glucose level or liver enzymes activity in rats after 2-week treatment. We also showed that none of the compounds possessed antioxidant or cytotoxic properties at antidepressant- and anxiolytic-like doses. HBK-14 and HBK-15 very weakly blocked H1 receptors in guinea pig ileum. Positive results of our preliminary experiments on the safety of HBK-14 and HBK-15 encourage further studies concerning their effectiveness in the treatment of depression and/or anxiety disorders.

  17. A quantitative histochemical procedure for the demonstration of purine nucleoside phosphorylase activity in rat and human liver using Tetranitro BT and xanthine oxidase as auxiliary enzyme

    NARCIS (Netherlands)

    Frederiks, W. M.; Bosch, K. S.; van Gulik, T.

    1993-01-01

    A quantitative histochemical procedure was developed for the demonstration of purine nucleoside phosphorylase in rat liver using unfixed cryostat sections and the auxiliary enzyme xanthine oxidase. The optimum incubation medium contained 18% (w/v) poly(vinyl alcohol), 100 mM phosphate buffer, pH

  18. Gene polymorphisms of desaturase enzymes of polyunsaturated fatty acid metabolism and adiponutrin and the increased risk of nonalcoholic fatty liver disease

    OpenAIRE

    Manvi Vernekar; Deepak Amarapurkar; Kalpana Joshi; Rekha Singhal

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is considered to be the hepatic manifestation of the metabolic syndrome (MetS). Adiponutrin gene polymorphisms have been associated with NAFLD worldwide. Polyunsaturated fatty acids (PUFAs) have been studied to have anti-inflammatory effects and plasma lipid lowering properties. PUFAs are endogenously synthesized with the help of delta-6-desaturase and delta-5-desaturase enzymes. They are encoded by FADS2 and FADS1 genes respectively. Polymorphisms in ...

  19. Hepatic Rupture Caused by Hemolysis, Elevated Liver Enzyme, and Low Platelet Count Syndrome: A Case Report with Computed Tomographic and Conventional Angiographic Findings

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Cheong Bok; Ahn, Jae Hong; Choi, Soo Jung; Lee, Jong Hyeog; Park, Man Soo; Jung, Seung Mun; Ryu, Dae Sik [Dept. of Radiology, Asan Foundation, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung (Korea, Republic of)

    2013-03-15

    The authors recently obtained successful clinical outcome after embolization of the hepatic artery and right inferior phrenic artery in a pregnant patient with hemolysis, elevated liver enzyme, and low platelet count (HELLP) syndrome causing hepatic rupture. We report the computed tomographic and conventional angiographic findings in a case of HELLP syndrome, resulting in hepatic infarction and rupture with active bleeding.

  20. Long-term effect of medium-chain triglyceride on hepatic enzymes catalyzing lipogenesis and cholesterogenesis in rats

    International Nuclear Information System (INIS)

    Takase, Sachiko; Morimoto, Ayami; Nakanishi, Mayumi; Muto, Yasutoshi.

    1977-01-01

    This study was conducted to investigate the long-term effect of dietary medium-chain triglyceride (MCT) as compared with that of corn oil feeding on lipid metabolism in rats. Both serum cholesterol and triglyceride levels in MCT-fed rats showed significant decrease during the experimental period of eight weeks, although liver cholesterol and triglyceride contents were not distinguishable between the two groups. Significant elevation of the activity of lipogenic enzymes, such as fatty acid synthetase (FAS) and malic enzyme (ME) of the liver, was observed in MCT-fed rats without any fat accumulation of the liver (fatty liver). The increase of lipogenic enzyme activity was accompanied by a significant reduction of essential fatty acids (EFA) such as 18:2 (ωsigma) and 20:4 (ωsigma) in total liver lipid. In contrast, hepatic β-hydroxy-β-methylglutaryl CoA(HMG-CoA) reductase activity was significantly decreased in MCT-fed rats, that would play an important role in achieving hypocholesterolemia. From these results obtained in a long-term experiment, it is concluded that exogenous MCT depresses the key enzyme catalyzing cholesterol synthesis with a concomitant elevation of lipogenic enzyme activity in the rat liver. (auth.)

  1. High prevalence of abnormal liver enzymes in South African patients ...

    African Journals Online (AJOL)

    Objective: To determine the prevalence of liver function test abnormalities in South African black and Indian adult patients with type 2 diabetes mellitus attending a tertiary diabetes clinic. iabetes clinic. Recorded data included the past medical and drug history, history of alcohol abuse, anthropometry, lipid profile and liver ...

  2. Targeting of superoxide dismutase to the liver results in anti-inflammatory effects in rats with fibrotic livers

    NARCIS (Netherlands)

    Swart, P J; Hirano, T; Kuipers, M E; Ito, Y; Smit, C; Hashida, M; Nishikawa, M; Beljaars, L; Meijer, D K; Poelstra, K

    1999-01-01

    Background/Aims: The rapid clearance from plasma and the limited uptake of superoxide dismutase (SOD) in the liver hampers the effectiveness of this enzyme in liver diseases. We therefore compared the pharmacokinetics and in vivo efficacy of SOD with two modified forms of this protein: SOD coupled

  3. Trapping of cis-2-butene-1,4-dial to measure furan metabolism in human liver microsomes by cytochrome P450 enzymes.

    Science.gov (United States)

    Gates, Leah A; Lu, Ding; Peterson, Lisa A

    2012-03-01

    Furan is a liver toxicant and carcinogen in rodents. It is classified as a possible human carcinogen, but the human health effects of furan exposure remain unknown. The oxidation of furan by cytochrome P450 (P450) enzymes is necessary for furan toxicity. The product of this reaction is the reactive α,β-unsaturated dialdehyde, cis-2-butene-1,4-dial (BDA). To determine whether human liver microsomes metabolize furan to BDA, a liquid chromatography/tandem mass spectrometry method was developed to detect and quantify BDA by trapping this reactive metabolite with N-acetyl-l-cysteine (NAC) and N-acetyl-l-lysine (NAL). Reaction of NAC and NAL with BDA generates N-acetyl-S-[1-(5-acetylamino-5-carboxypentyl)-1H-pyrrol-3-yl]-l-cysteine (NAC-BDA-NAL). Formation of NAC-BDA-NAL was quantified in 21 different human liver microsomal preparations. The levels of metabolism were comparable to that observed in F-344 rat and B6C3F1 mouse liver microsomes, two species known to be sensitive to furan-induced toxicity. Studies with recombinant human liver P450s indicated that CYP2E1 is the most active human liver furan oxidase. The activity of CYP2E1 as measured by p-nitrophenol hydroxylase activity was correlated to the extent of NAC-BDA-NAL formation in human liver microsomes. The formation of NAC-BDA-NAL was blocked by CYP2E1 inhibitors but not other P450 inhibitors. These results suggest that humans are capable of oxidizing furan to its toxic metabolite, BDA, at rates comparable to those of species sensitive to furan exposure. Therefore, humans may be susceptible to furan's toxic effects.

  4. Disturbances in lysosomal enzymes activity in rats, following experimental postradiation disease

    International Nuclear Information System (INIS)

    Drozdz, M.; Piwowarczyk, B.; Olczyk, K.; Pikula-Zachara, M.

    1981-01-01

    The studies were aimed at detecting the biological effects of radiation on rat's organism, through studying the activity of lysosomal enzymes in blood plasma and some organs. The contemporary studies suggest that lysosomes play an important role in the occurrence and course of postradiation disease. The obtained results suggest the multidirectional gamma-rays effects on lysosomal enzymes response in serum, leucocytes, liver lysosomes and in liver, kidneys, lungs, heart. Increased activity of acid phosphatase, beta-glucoronidase and beta-acetyl-glucosaminase in the tissues of irradiated animals indicates that gamma rays labilizate the lysosomal membrane. The range of changes indicates a selective nature of this phenomenon. Kidneys, lungs and liver appeared the most ray-sensitive organs. The activity of acid phosphatase was found to be most increased in blood serum and leucocytes. The activity of all examined enzymes in liver lysosomes was decreased. Acid phosphatase exhibited the greatest activity increases. Lysosomal responses are indicative of the degree of destructive or regenerative changes in the organism. (author)

  5. Expression and kinetic properties of a recombinant 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase isoenzyme of human liver.

    Science.gov (United States)

    Deyashiki, Y; Tamada, Y; Miyabe, Y; Nakanishi, M; Matsuura, K; Hara, A

    1995-08-01

    Human liver cytosol contains multiple forms of 3 alpha-hydroxysteroid dehydrogenase and dihydrodiol dehydrogenase with hydroxysteroid dehydrogenase activity, and multiple cDNAs for the enzymes have been cloned from human liver cDNA libraries. To understand the relationship of the multiple enzyme froms to the genes, a cDNA, which has been reported to code for an isoenzyme of human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase, was expressed in Escherichia coli. The recombinant enzyme showed structural and functional properties almost identical to those of the isoenzyme purified from human liver. In addition, the recombinant isoenzyme efficiently reduced 5 alpha-dihydrotestosterone and 5 beta-dihydrocortisone, the known substrates of human liver 3 alpha-hydroxysteroid dehydrogenase and chlordecone reductase previously purified, which suggests that these human liver enzymes are identical. Furthermore, the steady-state kinetic data for NADP(+)-linked (S)-1-indanol oxidation by the recombinant isoenzyme were consistent with a sequential ordered mechanism in which NADP+ binds first. Phenolphthalein inhibited this isoenzyme much more potently than it did the other human liver dihydrodiol dehydrogenases, and was a competitive inhibitor (Ki = 20 nM) that bound to the enzyme-NADP+ complex.

  6. Markers of liver function and inflammatory cytokines modulation by ...

    African Journals Online (AJOL)

    Conclusion: Aerobic exercise training modulates inflammatory cytokine levels and markers of liver function in patients with nonalcoholic ... and is associated with over nutrition and under activity, ... of these subjects with leptin reduced liver fat and liver enzyme ... tissue, muscle-released interleukin-6 inhibition of tumor.

  7. HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology.

    Science.gov (United States)

    Berndt, Nikolaus; Bulik, Sascha; Wallach, Iwona; Wünsch, Tilo; König, Matthias; Stockmann, Martin; Meierhofer, David; Holzhütter, Hermann-Georg

    2018-06-19

    The epidemic increase of non-alcoholic fatty liver diseases (NAFLD) requires a deeper understanding of the regulatory circuits controlling the response of liver metabolism to nutritional challenges, medical drugs, and genetic enzyme variants. As in vivo studies of human liver metabolism are encumbered with serious ethical and technical issues, we developed a comprehensive biochemistry-based kinetic model of the central liver metabolism including the regulation of enzyme activities by their reactants, allosteric effectors, and hormone-dependent phosphorylation. The utility of the model for basic research and applications in medicine and pharmacology is illustrated by simulating diurnal variations of the metabolic state of the liver at various perturbations caused by nutritional challenges (alcohol), drugs (valproate), and inherited enzyme disorders (galactosemia). Using proteomics data to scale maximal enzyme activities, the model is used to highlight differences in the metabolic functions of normal hepatocytes and malignant liver cells (adenoma and hepatocellular carcinoma).

  8. The relationship between sugar-sweetened beverages and liver enzymes among healthy premenopausal women: a prospective cohort study.

    Science.gov (United States)

    Shimony, Maya K; Schliep, Karen C; Schisterman, Enrique F; Ahrens, Katherine A; Sjaarda, Lindsey A; Rotman, Yaron; Perkins, Neil J; Pollack, Anna Z; Wactawski-Wende, Jean; Mumford, Sunni L

    2016-03-01

    To prospectively assess the association between sugar-sweetened beverages (SSB), added sugar, and total fructose and serum concentrations of liver enzymes among healthy, reproductive-age women. A prospective cohort of 259 premenopausal women (average age 27.3 ± 8.2 years; BMI 24.1 ± kg/m(2)) were followed up for up to two menstrual cycles, providing up to eight fasting blood specimens/cycle and four 24-h dietary recalls/cycle. Women with a history of chronic disease were excluded. Alanine and aspartate aminotransferases (ALT and AST, respectively) were measured in serum samples. Linear mixed models estimated associations between average SSB, added sugar, and total fructose intake and log-transformed liver enzymes adjusting for age, race, body mass index, total energy and alcohol intake, and Mediterranean diet score. For every 1 cup/day increase in SSB consumption and 10 g/day increase in added sugar and total fructose, log ALT increased by 0.079 U/L (95 % CI 0.022, 0.137), 0.012 U/L (95 % CI 0.002, 0.022), and 0.031 (0.012, 0.050), respectively, and log AST increased by 0.029 U/L (-0.011, 0.069), 0.007 U/L (0.000, 0.014), and 0.017 U/L (0.004, 0.030), respectively. Women who consumed ≥1.50 cups/day (12 oz can) SSB versus less had 0.127 U/L (95 % CI 0.001, 0.254) higher ALT [percent change 13.5 % (95 % CI 0.1, 28.9)] and 0.102 (95 % CI 0.015, 0.190) higher AST [percent change 10.8 % (95 % CI 1.5, 20.9)]. Sugar-sweetened beverages were associated with higher serum ALT and AST concentrations among healthy premenopausal women, indicating that habitual consumption of even moderate SSB may elicit hepatic lipogenesis.

  9. Mitochondrial DNA Unwinding Enzyme Required for Liver Regeneration | Center for Cancer Research

    Science.gov (United States)

    The liver has an exceptional capacity to proliferate. This ability allows the liver to regenerate its mass after partial surgical removal or injury and is the key to successful partial liver transplants. Liver cells, called hepatocytes, are packed with mitochondria, and regulating mitochondrial DNA (mtDNA) copy number is crucial to mitochondrial function, including energy production, during proliferation. Yves Pommier, M.D., Ph.D., of CCR’s Developmental Therapeutics Branch, and his colleagues recently showed that the vertebrate mitochondrial topoisomerase, Top1mt, was critical in maintaining mitochondrial function in the heart after doxorubicin-induced damage. The group wondered whether Top1mt might play a similar role in liver regeneration.

  10. Effects of antiretroviral agents during pregnancy on liver enzymes and amylase in HIV-exposed, uninfected newborn infants

    Directory of Open Access Journals (Sweden)

    Patrícia El Beitune

    Full Text Available This study assessed the effect of antiretroviral drugs administered to pregnant women on amylase and liver enzymes of the neonate. A prospective study was conducted on 52 neonates divided into three groups: infants born to HIV-infected mothers taking zidovudine (ZDV group, n = 18, infants born to mothers taking zidovudine + lamivudine + nelfinavir (TT group, n = 22 and infants born to normal women (control group, n = 12. Umbilical cord blood from the newborn infant was used to determine liver transaminases and amylase. Data were analyzed statistically by nonparametric tests, with the level of significance set at p<0.05. The median levels for TT group newborns were 33.3 U/L for oxaloacetic transaminase, 21.5 U/L for pyruvic transaminase, 1.9 mg/dL for total bilirubin, 153 mg/dL for alkaline phosphatase, and 9.6 U/L for amylase. These results did not differ from those obtained for Control newborns or newborns exposed to ZDV alone. No association was observed between the use of antiretroviral drugs during pregnancy and adverse effects on neonatal amylase and hepatic parameters at birth.

  11. Investigation of the Enzyme activities of Alkaline Phosphatase, Lactate Dehydrogenase, Transaminase and Histopathological Changes of Liver after Exposure to NiO and NiO Nanoparticles in Rats

    Directory of Open Access Journals (Sweden)

    Aidin Marzban

    2017-08-01

    Conclusion: The results of this study demonstrate that exposure to different doses of NiONPs and NiO can induce different degrees of damage in a dose dependent manner. Thus, increasing level of liver enzymes and histopathological changes confirmed NiONPs and NiO toxicity.

  12. Budd-Chiari and inferior caval vein syndromes due to membranous obstruction of the liver veins. Successful treatment with angioplasty and transcaval TIPS

    DEFF Research Database (Denmark)

    Holland-Fischer, Peter

    2004-01-01

    The case is presented of a 25-year-old Caucasian patient with Budd-Chiari syndrome due to membranous obstruction of the liver veins and inferior caval vein syndrome as a result of secondary hyperplasia of the caudate lobe of the liver, obstructing the caval vein. Diagnosis was established...... that angioplasty and TIPS are safe and efficient procedures to reduce liver engorgement and complications of portal hypertension in selected patients with Budd-Chiari syndrome....

  13. Dicranostiga leptopodu (Maxim.) Fedde extracts attenuated CCl4-induced acute liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function.

    Science.gov (United States)

    Tang, Deping; Wang, Fang; Tang, Jinzhou; Mao, Aihong; Liao, Shiqi; Wang, Qin

    2017-01-01

    Dicranostiga Leptodu (Maxim.) fedde (DLF), a poppy plant, has been reported have many benefits and medicinal properties, including free radicals scavenging and detoxifying. However, the protective effect of DLF extracts against carbon tetrachloride (CCl 4 )-induced damage in mice liver has not been elucidated. Here, we demonstrated that DLF extracts attenuated CCl 4 -induced liver damage in mice through increasing anti-oxidative enzyme activity to improve mitochondrial function. In this study, the mice liver damage evoked by CCl 4 was marked by morphology changes, significant rise in lipid peroxidation, as well as alterations of mitochondrial respiratory function. Interestingly, pretreatment with DLF extracts attenuated CCl 4 -induced morphological damage and increasing of lipid peroxidation in mice liver. Additionally, DLF extracts improved mitochondrial function by preventing the disruption of respiratory chain and suppression of mitochondrial Na + K + -ATPase and Ca 2+ -ATPase activity. Furthermore, administration with DLF extracts elevated superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels and maintained the balance of redox status. This results showed that toxic protection effect of DLF extracts on mice liver is mediated by improving mitochondrial respiratory function and keeping the balance of redox status, which suggesting that DLF extracts could be used as potential toxic protection agent for the liver against hepatotoxic agent. Copyright © 2016. Published by Elsevier Masson SAS.

  14. Physiologic Effect of Stent Therapy for Inferior Vena Cava Obstruction Due to Malignant Liver Tumor

    International Nuclear Information System (INIS)

    Kishi, Kazushi; Sonomura, Tetsuo; Fujimoto, Hisashi; Kimura, Masashi; Yamada, Katsuya; Sato, Morio; Juri, Masanobu

    2006-01-01

    Purpose. To understand systemic the influence of stent therapy for inferior vena cava (IVC) obstruction due to advanced liver tumor. Methods. Seven patients with symptomatic IVC obstruction due to advanced primary (n 4) or secondary (n = 3) liver tumor were subjected to stent therapy. Enrollment criteria included high IVC pressure over 15 mmHg and the presence of edema and ascites. Z-stents were deployed using coaxial sheath technique via femoral venous puncture. Physiologic and hematobiochemical parameters were analyzed. Results. All procedures were successful, and the stents remained patent until patient death. Promptly after stent placement, the IVC flow recovered, and the venous blood pressure in the IVC below the obstruction level showed a significant decrease from 20.8 ± 1.2 mmHg (mean ± SE) to 10.7 ± 0.7 mmHg (p 0.6) with the urine volume increase, and with the decreased volume of edema and ascites. The urine volume increase correlated well with the decrement of edema, but not with that of ascites. Improvements for various durations in the levels of blood urea nitrogen, serum creatinine, lactate dehydrogenase, fibrinogen, and platelet count were found (p < 0.05). These hematobiochemical changes were well correlated with each other and with the decrement of ascites. Two patients showed a low blood sodium level of 128.5 mEq/l after intensive natriuresis, and one of them died on day 21 with hepatic failure, which was interpreted as maladaptation aggravation. The mean survival time was 94.1 ± 34.1 days (mean ± SD), ranging from 21 to 140 days after stent treatment. Conclusion. The stent therapy for IVC obstruction due to malignant liver tumors was followed by a series of physiologic and hematobiochemical consequences, most of them favorable but some possibly unfavorable. Rational interpretations and predictions of sequelae based on physiologic science including cardiology, hepatology, and nephrology would facilitate the best management of stent therapy for

  15. Liver enzymes and psychological well-being response to aerobic exercise training in patients with chronic hepatitis C.

    Science.gov (United States)

    Abd El-Kader, Shehab M; Al-Jiffri, Osama H; Al-Shreef, Fadwa M

    2014-06-01

    Chronic hepatitis C (CHC) is a medical condition that has broad implications for a person's physical and psychological health. The aim of this study was to detect changes in liver enzymes and psychological well-being in response to aerobic exercise training in patients with CHC. Fifty CHC patients were included in two equal groups. The first group (A) received aerobic exercise training in addition to their regular medical treatment. The second group (B) received no training and only has their regular medical treatment. The program consisted of three sessions per week for three months. There was a significant decrease in mean values of Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Gamma - Glutamyltransferase (GGT), Beck Depression Inventory (BDI ) & Profile of Mood States(POMS) and increase in Rosenberg Self-Esteem Scale (RSES) in group (A) after treatments, but the changes in group (B) were not significant. Also, there were significant differences between mean levels of the investigated parameters in group (A) and group (B) at the end of the study. Aerobic exercise training improves hepatic enzymes and psychological well-being in patients with chronic hepatitis C.

  16. Extracellular vesicles from human liver stem cells restore argininosuccinate synthase deficiency.

    Science.gov (United States)

    Herrera Sanchez, Maria Beatriz; Previdi, Sara; Bruno, Stefania; Fonsato, Valentina; Deregibus, Maria Chiara; Kholia, Sharad; Petrillo, Sara; Tolosano, Emanuela; Critelli, Rossana; Spada, Marco; Romagnoli, Renato; Salizzoni, Mauro; Tetta, Ciro; Camussi, Giovanni

    2017-07-27

    Argininosuccinate synthase (ASS)1 is a urea cycle enzyme that catalyzes the conversion of citrulline and aspartate to argininosuccinate. Mutations in the ASS1 gene cause citrullinemia type I, a rare autosomal recessive disorder characterized by neonatal hyperammonemia, elevated citrulline levels, and early neonatal death. Treatment for this disease is currently restricted to liver transplantation; however, due to limited organ availability, substitute therapies are required. Recently, extracellular vesicles (EVs) have been reported to act as intercellular transporters carrying genetic information responsible for cell reprogramming. In previous studies, we isolated a population of stem cell-like cells known as human liver stem cells (HLSCs) from healthy liver tissue. Moreover, EVs derived from HLSCs were reported to exhibit regenerative effects on the liver parenchyma in models of acute liver injury. The aim of this study was to evaluate whether EVs derived from normal HLSCs restored ASS1 enzymatic activity and urea production in hepatocytes differentiated from HLSCs derived from a patient with type I citrullinemia. HLSCs were isolated from the liver of a patient with type I citrullinemia (ASS1-HLSCs) and characterized by fluorescence-activated cell sorting (FACS), immunofluorescence, and DNA sequencing analysis. Furthermore, their differentiation capabilities in vitro were also assessed. Hepatocytes differentiated from ASS1-HLSCs were evaluated by the production of urea and ASS enzymatic activity. EVs derived from normal HLSCs were purified by differential ultracentrifugation followed by floating density gradient. The EV content was analyzed to identify the presence of ASS1 protein, mRNA, and ASS1 gene. In order to obtain ASS1-depleted EVs, a knockdown of the ASS1 gene in HLSCs was performed followed by EV isolation from these cells. Treating ASS1-HLSCs with EVs from HLSCs restored both ASS1 activity and urea production mainly through the transfer of ASS1 enzyme

  17. A fundamental trade-off in covalent switching and its circumvention by enzyme bifunctionality in glucose homeostasis.

    Science.gov (United States)

    Dasgupta, Tathagata; Croll, David H; Owen, Jeremy A; Vander Heiden, Matthew G; Locasale, Jason W; Alon, Uri; Cantley, Lewis C; Gunawardena, Jeremy

    2014-05-09

    Covalent modification provides a mechanism for modulating molecular state and regulating physiology. A cycle of competing enzymes that add and remove a single modification can act as a molecular switch between "on" and "off" and has been widely studied as a core motif in systems biology. Here, we exploit the recently developed "linear framework" for time scale separation to determine the general principles of such switches. These methods are not limited to Michaelis-Menten assumptions, and our conclusions hold for enzymes whose mechanisms may be arbitrarily complicated. We show that switching efficiency improves with increasing irreversibility of the enzymes and that the on/off transition occurs when the ratio of enzyme levels reaches a value that depends only on the rate constants. Fluctuations in enzyme levels, which habitually occur due to cellular heterogeneity, can cause flipping back and forth between on and off, leading to incoherent mosaic behavior in tissues, that worsens as switching becomes sharper. This trade-off can be circumvented if enzyme levels are correlated. In particular, if the competing catalytic domains are on the same protein but do not influence each other, the resulting bifunctional enzyme can switch sharply while remaining coherent. In the mammalian liver, the switch between glycolysis and gluconeogenesis is regulated by the bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2). We suggest that bifunctionality of PFK-2/FBPase-2 complements the metabolic zonation of the liver by ensuring coherent switching in response to insulin and glucagon.

  18. Molecular cloning and nucleotide sequence of cDNA for human liver arginase

    International Nuclear Information System (INIS)

    Haraguchi, Y.; Takiguchi, M.; Amaya, Y.; Kawamoto, S.; Matsuda, I.; Mori, M.

    1987-01-01

    Arginase (EC3.5.3.1) catalyzes the last step of the urea cycle in the liver of ureotelic animals. Inherited deficiency of the enzyme results in argininemia, an autosomal recessive disorder characterized by hyperammonemia. To facilitate investigation of the enzyme and gene structures and to elucidate the nature of the mutation in argininemia, the authors isolated cDNA clones for human liver arginase. Oligo(dT)-primed and random primer human liver cDNA libraries in λ gt11 were screened using isolated rat arginase cDNA as a probe. Two of the positive clones, designated λ hARG6 and λ hARG109, contained an overlapping cDNA sequence with an open reading frame encoding a polypeptide of 322 amino acid residues (predicted M/sub r/, 34,732), a 5'-untranslated sequence of 56 base pairs, a 3'-untranslated sequence of 423 base pairs, and a poly(A) segment. Arginase activity was detected in Escherichia coli cells transformed with the plasmid carrying λ hARG6 cDNA insert. RNA gel blot analysis of human liver RNA showed a single mRNA of 1.6 kilobases. The predicted amino acid sequence of human liver arginase is 87% and 41% identical with those of the rat liver and yeast enzymes, respectively. There are several highly conserved segments among the human, rat, and yeast enzymes

  19. Short-term hepatic effects of depleted uranium on xenobiotic and bile acid metabolizing cytochrome P450 enzymes in the rat

    International Nuclear Information System (INIS)

    Gueguen, Y.; Souidi, M.; Baudelin, C.; Dudoignon, N.; Grison, S.; Dublineau, I.; Marquette, C.; Voisin, P.; Gourmelon, P.; Aigueperse, J.

    2006-01-01

    The toxicity of uranium has been demonstrated in different organs, including the kidneys, skeleton, central nervous system, and liver. However, few works have investigated the biological effects of uranium contamination on important metabolic function in the liver. In vivo studies were conducted to evaluate its effects on cytochrome P450 (CYP) enzymes involved in the metabolism of cholesterol and xenobiotics in the rat liver. The effects of depleted uranium (DU) contamination on Sprague-Dawley were measured at 1 and 3 days after exposure. Biochemical indicators characterizing liver and kidney functions were measured in the plasma. The DU affected bile acid CYP activity: 7α-hydroxycholesterol plasma level decreased by 52% at day 3 whereas microsomal CYP7A1 activity in the liver did not change significantly and mitochondrial CYP27A1 activity quintupled at day 1. Gene expression of the nuclear receptors related to lipid metabolism (FXR and LXR) also changed, while PPARα mRNA levels did not. The increased mRNA levels of the xenobiotic-metabolizing CYP3A enzyme at day 3 may be caused by feedback up-regulation due to the decreased CYP3A activity at day 1. CAR mRNA levels, which tripled on day 1, may be involved in this up-regulation, while mRNA levels of PXR did not change. These results indicate that high levels of depleted uranium, acting through modulation of the CYP enzymes and some of their nuclear receptors, affect the hepatic metabolism of bile acids and xenobiotics. (orig.)

  20. Radiation Exposure Alters Expression of Metabolic Enzyme Genes in Mice

    Science.gov (United States)

    Wotring, V. E.; Mangala, L. S.; Zhang, Y.; Wu, H.

    2011-01-01

    Most administered pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand the effects of spaceflight on the enzymes of the liver and exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. Additionally, it has been previous noted that pre-exposure to small radiation doses seems to confer protection against later and larger radiation doses. This protective power of pre-exposure has been called a priming effect or radioadaptation. This study is an effort to examine the drug metabolizing effects of radioadaptation mechanisms that may be triggered by early exposure to low radiation doses.

  1. Niemann-Pick type C2 protein supplementation in experimental non-alcoholic fatty liver disease

    DEFF Research Database (Denmark)

    Christensen, Claus Uhrenholt; Glavind, Emilie; Thomsen, Karen Louise

    2018-01-01

    the last two weeks or the entire four weeks. End-points were liver/body- and spleen/body weight ratios, histopathological NASH scores, fibrosis, serum liver enzymes, cholesterol, lipoproteins, cytokines, and quantitative polymerase chain reaction derived hepatic gene expression related to cholesterol...... metabolism, inflammation, and fibrosis. RESULTS: HFHC rats developed hepatomegaly, non-fibrotic NASH histopathology, elevated liver enzymes, serum cholesterol, and pro-inflammatory cytokines. Their sterol regulatory element binding factor 2 (SREBF2) and low-density lipoprotein receptor (LDL-R) mRNAs were...... down-regulated compared with rats on standard chow. NPC2 did not improve liver weight, histopathology, levels of serum liver enzymes or pro-inflammatory tumor necrosis factor-α (TNFα), Interleukin (IL)-6, or IL-1β in HFHC rats. Two weeks of NPC2 treatment lowered hepatic TNFα and COL1A1 mRNA expression...

  2. Dose-Dependent Change in Elimination Kinetics of Ethanol due to Shift of Dominant Metabolizing Enzyme from ADH 1 (Class I to ADH 3 (Class III in Mouse

    Directory of Open Access Journals (Sweden)

    Takeshi Haseba

    2012-01-01

    Full Text Available ADH 1 and ADH 3 are major two ADH isozymes in the liver, which participate in systemic alcohol metabolism, mainly distributing in parenchymal and in sinusoidal endothelial cells of the liver, respectively. We investigated how these two ADHs contribute to the elimination kinetics of blood ethanol by administering ethanol to mice at various doses, and by measuring liver ADH activity and liver contents of both ADHs. The normalized AUC (AUC/dose showed a concave increase with an increase in ethanol dose, inversely correlating with β. CLT (dose/AUC linearly correlated with liver ADH activity and also with both the ADH-1 and -3 contents (mg/kg B.W.. When ADH-1 activity was calculated by multiplying ADH-1 content by its Vmax⁡/mg (4.0 and normalized by the ratio of liver ADH activity of each ethanol dose to that of the control, the theoretical ADH-1 activity decreased dose-dependently, correlating with β. On the other hand, the theoretical ADH-3 activity, which was calculated by subtracting ADH-1 activity from liver ADH activity and normalized, increased dose-dependently, correlating with the normalized AUC. These results suggested that the elimination kinetics of blood ethanol in mice was dose-dependently changed, accompanied by a shift of the dominant metabolizing enzyme from ADH 1 to ADH 3.

  3. Correlation of liver enzymes and sonographic findings with pulsatile index of middle cerebral and basilar arteries in nonalcoholic fatty liver

    Directory of Open Access Journals (Sweden)

    Gholamreza Rezamand

    2014-04-01

    Conclusion: Considering the increase of cerebral arteries PI in advanced liver disease, absence of increase in vascular PI of patients in the present study could be attributed to the short duration of disease from diagnosis to perform TCD, lack of advanced liver involvement (absence of liver dysfunction and the response effect to treatment before the TCD. Therefore, to assess vascular changes over time, repeating the TCD with assess other parameters such as Fibroscan and K18 factor that has more compatibility of liver function, could help to understand the pathophysiology of liver diseases and its effect on vascular resistance.

  4. Cholesterol esterification by mouse liver homogenate. Contribution to the study of ACYL-CoA: Cholesterol ACYL transferase in mammalian liver

    International Nuclear Information System (INIS)

    Soares, M.G.C.B.

    1976-01-01

    A cholesterol- esterifying enzyme from mouse liver has been partially characterized. The enzyme which showed optimum activity at pH 7,1 and required ATP and CoA, was identified as an acyl CoA: cholesterol acyl transferase (E.C.2.3.1.26). As a fuction of time the percentage of esterified cholesterol increased linearly during the first hour of incubation and continued to increase but not linearly with 4 hours, after which time no further net esterefication was observed. The relative concentration of esterified cholesterol remained constant between the fourth and twelveth hours of incubation but afterwards decreased when the incubation continued until 24 hours. The cholesterol- esterifying activity was 24,0+- 2,9 nmoles cholesterol esterified per gram tissue wet weight per minute. The mean percentages of free cholesterol esterified in and 24 hours respectively were 14,8+- 1,6 e 21,9+- 4,5. The subfractionation of labelled cholesteryl esters after one hour incubation of liver homogenate with 4-C 14 -Cholesterol showed the order of preference for the formation of the different ester classes to be monounsatured > diunsatured ≥ saturated >> polyunsaturated. The properties of the enzyme frommouse liver do not markedly differ from those of the previously recorded ACAT activity of rat liver. (Author) [pt

  5. Where should the safe limits of alcohol consumption stand in light of liver enzyme abnormalities in alcohol consumers?

    Directory of Open Access Journals (Sweden)

    Onni Niemelä

    Full Text Available To estimate the prevalence and risk factors for abnormal liver enzymes in a large age- and gender stratified population-based sample of apparently healthy individuals with or without alcohol consumption and other health-related risk factors (adiposity, physical inactivity, smoking.Data on alcohol use, smoking, diet and physical activity were recorded using structured questionnaires from 13,976 subjects (6513 men, 7463 women, aged 25-74 years in the national FINRISK studies. Alcohol data was used to categorize the participants into abstainers, light drinkers, moderate drinkers and heavy drinkers. Serum gamma-glutamyltransferase (GGT and alanine aminotransferase (ALT activities were measured using standard kinetic methods.Male light drinkers, moderate drinkers and heavy drinkers showed significantly higher relative risks of abnormal GGT than abstainers: 1.37 (95% confidence interval 1.11 to 1.71, p < 0.01, 2.72 (2.08 to 3.56, p < 0.0005, and 6.10 (4.55 to 7.17, p < 0.0005, respectively. Corresponding values for women were 1.22 (0.99 to 1.51, p = 0.065, 1.90 (1.44 to 2.51, p < 0.0005, and 5.91 (3.80 to 9.17, p < 0.0005. Estimated threshold doses for a significant GGT elevation was 14 standard weekly alcohol doses for men and 7 for women. Excess body weight and age over 40 years modulated the thresholds towards smaller quantities of alcohol. The risk of abnormal GGT was also significantly influenced by physical inactivity and smoking. The relative risks of abnormal ALT activities were increased in male heavy drinkers, especially in those presenting with adiposity and sedentary lifestyle.Alcohol use markedly increases the risk for abnormal liver enzyme activities in those presenting with age over 40 years, obesity, smoking or sedentary lifestyle. The data should be considered in public health recommendations and in the definitions of safe limits of alcohol use.

  6. Prostaglandin levels and lysosomal enzyme activities in irradiated rats

    International Nuclear Information System (INIS)

    Trocha, P.J.; Catravas, G.N.

    1980-01-01

    Whole-body irradiation of rats results in the release of hydrolases from lysosomes, an increase in lysosomal enzyme activities, and changes in the prostaglandin levels in spleen and liver tissues. A transient increase in the concentration of prostaglandins E and F and leakage of lysosomal hydrolases occurred in both spleen and liver tissues 3-6 hours after the animals were irradiated. Maximal values for hydrolase activities, prostaglandin E and F content, and release of lysosomal enzymes were found 4 days postirradiation in rat spleens whereas in the liver only slight increases were observed at this time period for prostaglandin F levels. On day 7 there was a final rise in the spleen's prostaglandin E and F concentrations and leakage of hydrolases from the lysosomes before returning to near normal values on day 11. The prostaglandin F concentration in liver was also slightly elevated on the 7th day after irradiation and then decreased to control levels. (author)

  7. A novel marker for assessment of liver matrix remodeling: An enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M)

    DEFF Research Database (Denmark)

    Leeming, Diana Julie; He, Y.; Veidal, S. S.

    2011-01-01

    A competitive enzyme-linked immunosorbent assay (ELISA) for detection of a type I collagen fragment generated by matrix metalloproteinases (MMP) -2, -9 and -13, was developed (CO1-764 or C1M). The biomarker was evaluated in two preclinical rat models of liver fibrosis: bile duct ligation (BDL) an...

  8. Coffee and liver health.

    Science.gov (United States)

    Morisco, Filomena; Lembo, Vincenzo; Mazzone, Giovanna; Camera, Silvia; Caporaso, Nicola

    2014-01-01

    Coffee is one of the most widely used beverages in the world. It includes a wide array of components that can have potential implications for health. Several epidemiological studies associate coffee consumption with a reduced incidence of various chronic diseases such as diabetes, cardiovascular diseases, and neurodegenerative diseases. Over the past 20 years, an increasing number of epidemiological and experimental studies have demonstrated the positive effects of coffee on chronic liver diseases. Coffee consumption has been inversely associated with the activity of liver enzymes in subjects at risk, including heavy drinkers. Coffee favours an improvement in hepatic steatosis and fibrosis, and a reduction in cirrhosis and the risk of hepatocellular carcinoma. The mechanisms of action through which it exerts its beneficial effects are not fully understood. Experimental studies show that coffee consumption reduces fat accumulation and collagen deposition in the liver and promotes antioxidant capacity through an increase in glutathione as well as modulation of the gene and protein expression of several inflammatory mediators. Animal and in vitro studies indicate that cafestol and kahweol, 2 diterpens, can operate by modulating multiple enzymes involved in the detoxification process of carcinogens causing hepatocellular carcinoma. It is unclear whether the benefits are significant enough to "treat" patients with chronic liver disease. While we await clarification, moderate daily unsweetened coffee use is a reasonable adjuvant to therapy for these patients.

  9. The Effects of Space Flight on Some Liver Enzymes Concerned with Carbohydrate and Lipid Metabolism in Rats

    Science.gov (United States)

    Abraham, S.; Lin, C. Y.; Klein, H. P.; Volkmann, C.

    1978-01-01

    The activities of about 30 enzymes concerned with carbohydrate and lipid metabolism and the levels of glycogen and of individual fatty acids were measured in livers of rats ex- posed to prolonged space flight (18.5 days) aboard COSMOS 986 Biosatellite. When flight stationary, (FS) and flight centrifuged (FC) rats were compared at recovery (R(sub 0)), decrceases in the activities of glycogen phosphorylase, alpha glycerphosphate, acyl transferase, diglyceride acyl transferase, acconitase and Epsilon-phosphogluconate dehydrogenase were noted in the weightless group (FS). The significance of these findings was strengthened since all activities, showing alterations at R(sub 0), returned to normal 25 days post-flight. Differences were also seen in levels of two liver constituents. When glycogen and total fatty acids of the two groups of flight animals were determined, differences that could be attributed to reduced gravity were observed, the FS group at R(sub 0) contained, on the average, more than twice the amount of glycogen than did controls ad a remarkable shift in the ratio of palmitate to palmitoleate were noted. These metabolic alterations appear to be unique to the weightless condition. Our data justify the conclusion that centrifugation during space flight is equivalent to terrestrial gravity.

  10. Enzymes and Inhibitors in Neonicotinoid Insecticide Metabolism

    Science.gov (United States)

    Shi, Xueyan; Dick, Ryan A.; Ford, Kevin A.; Casida, John E.

    2009-01-01

    Neonicotinoid insecticide metabolism involves considerable substrate specificity and regioselectivity of the relevant CYP450, aldehyde oxidase, and phase II enzymes. Human CYP450 recombinant enzymes carry out the following conversions: CYP3A4, 2C19 and 2B6 for thiamethoxam (TMX) to clothianidin (CLO); 3A4, 2C19 and 2A6 for CLO to desmethyl-CLO; 2C19 for TMX to desmethyl-TMX. Human liver aldehyde oxidase reduces the nitro substituent of CLO to nitroso much more rapidly than that of TMX. Imidacloprid (IMI), CLO and several of their metabolites do not give detectable N-glucuronides but 5-hydroxy-IMI, 4,5-diol-IMI and 4-hydroxy-thiacloprid are converted to O-glucuronides in vitro with mouse liver microsomes and UDP-glucuronic acid or in vivo in mice. Mouse liver cytosol with S-adenosylmethionine converts desmethyl-CLO to CLO but not desmethyl-TMX to TMX. Two organophosphorus CYP450 inhibitors partially block IMI, thiacloprid and CLO metabolism in vivo in mice, elevating the brain and liver levels of the parent compounds while reducing amounts of the hydroxylated metabolites. PMID:19391582

  11. Hepatic cholesterol ester hydrolase in human liver disease.

    Science.gov (United States)

    Simon, J B; Poon, R W

    1978-09-01

    Human liver contains an acid cholesterol ester hydrolase (CEH) of presumed lysosomal origin, but its significance is unknown. We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy. Histologically normal livers hydrolyzed 5.80 +/- 0.78 SEM mumoles of cholesterol ester per hr per g of liver protein (n, 10). Values were similar in alcoholic liver disease (n, 17), obstructive jaundice (n, 9), and miscellaneous hepatic disorders (n, 21). In contrast, mean hepatic CEH activity was more than 3-fold elevated in 12 patients with acute hepatitis, 21.05 +/- 2.45 SEM mumoles per hr per g of protein (P less than 0.01). In 2 patients studied serially, CEH returned to normal as hepatitis resolved. CEH activity in all patients paralleled SGOT levels (r, 0.84; P less than 0.01). There was no correlation with serum levels of free or esterified cholesterol nor with serum activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. These studies confirm the presence of CEH activity in human liver and show markedly increased activity in acute hepatitis. The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study.

  12. Purification of camel liver catalase by zinc chelate affinity chromatography and pH gradient elution: An enzyme with interesting properties.

    Science.gov (United States)

    Chafik, Abdelbasset; Essamadi, Abdelkhalid; Çelik, Safinur Yildirim; Mavi, Ahmet

    2017-12-01

    Climate change and increasing temperatures are global concerns. Camel (Camelus dromedarius) lives most of its life under high environmental stress in the desert and represent ideal model for studying desert adaptation among mammals. Catalase plays a key role in protecting cells against oxidative stress. For the first time, catalase from camel liver was purified to homogeneity by zinc chelate affinity chromatography using pH gradient elution, a better separation was obtained. A purification fold of 201.81 with 1.17% yield and a high specific activity of 1132539.37U/mg were obtained. The native enzyme had a molecular weight of 268kDa and was composed of four subunits of equal size (65kDa). The enzyme showed optimal activity at a temperature of 45°C and pH 7.2. Thiol reagents, β-Mercaptoethanol and D,L-Dithiothreitol, inhibited the enzyme activity. The enzyme was inhibited by Al 3+ , Cd 2+ and Mg 2+ , whereas Ca 2+ , Co 2+ and Ni 2+ stimulated the catalase activity. Reduced glutathione has no effect on catalase activity. The K m and V max of the enzyme for hydrogen peroxide were 37.31mM and 6185157U/mg, respectively. Sodium azide inhibited the enzyme noncompetitively with K i value of 14.43μM, the IC 50 was found to be 16.71μM. The properties of camel catalase were different comparing to those of mammalian species. Relatively higher molecular weight, higher optimum temperature, protection of reduced glutathione from hydrogen peroxide oxidation and higher affinity for hydrogen peroxide and sodium azide, these could be explained by the fact that camel is able to live in the intense environmental stress in the desert. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Liver enzymes in patients with chronic kidney disease undergoing peritoneal dialysis and hemodialysis

    Directory of Open Access Journals (Sweden)

    Isabella Ramos de Oliveira Liberato

    2012-01-01

    hemodialysis session were significantly higher than the samples collected before the session. Taken together, the present data suggest that hemodilution could alter the serum levels of liver enzymes.

  14. Fixed Pupillary Light Reflex due to Peripheral Neuropathy after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Kwan Hyung Kim

    2015-08-01

    Full Text Available A 46-year-old female patient was admitted to the intensive care unit (ICU after liver transplantation. About an hour later after the ICU admission, she had no pupillary light reflex. Both pupils were also fixed at 5 mm. Patients who undergo liver transplantation are susceptible to neurologic disorders including hepatic encephalopathy, thromboembolism and intracranial hemorrhage. Abnormal pupillary light reflex usually indicates a serious neurologic emergency in these patients; however, benign neurologic disorders such as peripheral autonomic neuropathy or Holmes-Adie syndrome should also be considered. We experienced a case of fixed pupillary light reflex after liver transplantation diagnosed as peripheral autonomic neuropathy.

  15. Dipeptidylpeptidase-­IV, a key enzyme for the degradation of incretins and neuropeptides: activity and expression in the liver of lean and obese rats

    Directory of Open Access Journals (Sweden)

    E. Tarantola

    2012-10-01

    Full Text Available Given the scarcity of donors, moderately fatty livers (FLs are currently being considered as possible grafts for orthotopic liver transplantation (OLT, notwithstanding their poor tolerance to conventional cold preservation. The behaviour of parenchymal and sinusoidal liver cells during transplantation is being studied worldwide. Much less attention has been paid to the biliary tree, although this is considered the Achille’s heel even of normal liver transplantation. To evaluate the response of the biliary compartment of FLs to the various phases of OLT reliable markers are necessary. Previously we demonstrated that Alkaline Phosphatase was scarcely active in bile canaliculi of FLs and thus ruled it out as a marker. As an alternative, dipeptidylpeptidase-IV (DPP-IV, was investigated. This ecto-peptidase plays an important role in glucose metabolism, rapidly inactivating insulin secreting hormones (incretins that are important regulators of glucose metabolism. DPP-IV inhibitors are indeed used to treat Type II diabetes. Neuropeptides regulating bile transport and composition are further important substrates of DPP-IV in the enterohepatic axis. DPP-IV activity was investigated with an azo-coupling method in the liver of fatty Zucker rats (fa/fa, using as controls lean Zucker (fa/+ and normal Wistar rats. Protein expression was studied by immunofluorescence with the monoclonal antibody (clone 5E8. In Wistar rat liver, DPP-IV activity and expression were high in the whole biliary tree, and moderate in sinusoid endothelial cells, in agreement with the literature. Main substrates of DPP-IV in hepatocytes and cholangiocytes could be incretins GLP-1 and GIP, and neuropeptides such as vasoactive intestinal peptide (VIP and substance P, suggesting that these substances are inactivated or modified through the biliary route. In lean Zucker rat liver the enzyme reaction and protein expression patterns were similar to those of Wistar rat. In obese rat liver

  16. Effects of inhaled plutonium nitrate on bone and liver in dogs

    International Nuclear Information System (INIS)

    Dagle, G.E.; Weller, R.E.; Watson, C.R.; Buschbom, R.L.

    1994-04-01

    The life-span biological effects of inhaled soluble, alpha-emitting radionuclides deposited in the skeleton and liver were studied in 5 groups of 20 beagles exposed to initial lung depositions ranging from 0.48 to 518 Bq/g of lung. Average plutonium amounts in the lungs decreased to approximately 1% of the final body deposition in dogs surviving 5 years or more; more than 90% of the final depositions accumulated in the liver and skeleton. The liver-to-skeletal ratio of deposited plutonium was 0.83. The incidence of bone tumors, primarily osteogenic sarcomas causing early mortality, at final group average skeletal depositions of 15.8, 2.1, and 0.5 Bq/g was, respectively, 85%, 50%, and 5%; there were no bone tumors in exposure groups with mean average depositions lower than 0.5 Bq/g. Elevated serum liver enzyme levels were observed in exposure groups down to 1.3 Bq/g. The incidence of liver tumors at final group average liver depositions of 6.9, 1.3, 0.2, and 0.1 Bq/g, was, respectively, 25%, 15%, 15%, and 15%; one hepatoma occurred among 40 control dogs. The risk of the liver cancer produced by inhaled plutonium nitrate was difficult to assess due to the competing risks of life shortening from lung and bone tumors

  17. Stellate-cell lipidosis in liver biopsy specimens. Recognition and significance.

    Science.gov (United States)

    Levine, Pascale Hummel; Delgado, Yara; Theise, Neil D; West, A Brian

    2003-02-01

    Hepatic stellate-cell lipidosis due to hypervitaminosis A can lead to cirrhosis, which can be averted by restricting vitamin A intake. Other causes, including the use of synthetic retinoids, have been postulated. We studied the frequency and etiology of stellate-cell lipidosis in patients undergoing liver biopsy for reasons other than vitamin A abuse. Fourteen cases (1.1%) were identified retrospectively among 1,235 nontransplant liver biopsy specimens examined from January 1995 through December 1999. Diagnostic criteria included the following: lipid-laden cells in the space of Disse; small, dark, crescent-shaped nuclei with inconspicuous nucleoli; and wispy cytoplasmic strands separating fat droplets. Patient details, reason for biopsy, and medication use were studied. Reasons for biopsy included hepatitis C (10 cases), abnormal liver enzyme levels (2 cases), methotrexate use (1 case), and alcohol abuse (1 case). Hypervitaminosis A was not suspected clinically in the 5 patients who used oral vitamin A or 3 who used topical tretinoin (Retin-A). In 6 patients, no cause of stellate-cell lipidosis was discerned. Stellate-cell lipidosis should be reported to alert clinicians to a potentially preventable form of liver injury.

  18. Assessment of some Hepatic Enzyme activities in adult rabbits ...

    African Journals Online (AJOL)

    Therapeutic potentials of Garcinia kola (G. kola) have been extensively documented and several researches have asserted its protective uniqueness against liver disorders/diseases. It is the aim of this study to assess the level of some enzyme involved in liver cellular integrity in rabbits chronically fed G. kola. To achieve this ...

  19. Mechanism of activation of liver glycogen synthase by swelling

    NARCIS (Netherlands)

    Meijer, A. J.; Baquet, A.; Gustafson, L.; van Woerkom, G. M.; Hue, L.

    1992-01-01

    The mechanism linking the stimulation of liver glycogen synthesis to swelling induced either by amino acids or hypotonicity was studied in hepatocytes, in gel-filtered liver extracts, and in purified preparations of particulate glycogen to which glycogen-metabolizing enzymes are bound. High

  20. Redox imbalance due to the loss of mitochondrial NAD(P)-transhydrogenase markedly aggravates high fat diet-induced fatty liver disease in mice.

    Science.gov (United States)

    Navarro, Claudia D C; Figueira, Tiago R; Francisco, Annelise; Dal'Bó, Genoefa A; Ronchi, Juliana A; Rovani, Juliana C; Escanhoela, Cecilia A F; Oliveira, Helena C F; Castilho, Roger F; Vercesi, Anibal E

    2017-12-01

    The mechanisms by which a high fat diet (HFD) promotes non-alcoholic fatty liver disease (NAFLD) appear to involve liver mitochondrial dysfunctions and redox imbalance. We hypothesized that a HFD would increase mitochondrial reliance on NAD(P)-transhydrogenase (NNT) as the source of NADPH for antioxidant systems that counteract NAFLD development. Therefore, we studied HFD-induced liver mitochondrial dysfunctions and NAFLD in C57Unib.B6 congenic mice with (Nnt +/+ ) or without (Nnt -/- ) NNT activity; the spontaneously mutated allele (Nnt -/- ) was inherited from the C57BL/6J mouse substrain. After 20 weeks on a HFD, Nnt -/- mice exhibited a higher prevalence of steatohepatitis and content of liver triglycerides compared to Nnt +/+ mice on an identical diet. Under a HFD, the aggravated NAFLD phenotype in the Nnt -/- mice was accompanied by an increased H 2 O 2 release rate from mitochondria, decreased aconitase activity (a redox-sensitive mitochondrial enzyme) and higher susceptibility to Ca 2+ -induced mitochondrial permeability transition. In addition, HFD led to the phosphorylation (inhibition) of pyruvate dehydrogenase (PDH) and markedly reduced the ability of liver mitochondria to remove peroxide in Nnt -/- mice. Bypass or pharmacological reactivation of PDH by dichloroacetate restored the peroxide removal capability of mitochondria from Nnt -/- mice on a HFD. Noteworthy, compared to mice that were chow-fed, the HFD did not impair peroxide removal nor elicit redox imbalance in mitochondria from Nnt +/+ mice. Therefore, HFD interacted with Nnt mutation to generate PDH inhibition and further suppression of peroxide removal. We conclude that NNT plays a critical role in counteracting mitochondrial redox imbalance, PDH inhibition and advancement of NAFLD in mice fed a HFD. The present study provide seminal experimental evidence that redox imbalance in liver mitochondria potentiates the progression from simple steatosis to steatohepatitis following a HFD. Copyright

  1. Influence of Thyroxine on Blood Parameters and Liver Enzymes

    African Journals Online (AJOL)

    Dr Olaleye

    control group of twelve adult rats (six females and six males) received feed and water ... energy expenditure through actions on protein, carbohydrate and lipid metabolism. With specific regard to liver lipid metabolism, thyroid hormones.

  2. Serum paraoxonase-1 as biomarker for improved diagnosis of fatty liver in dairy cows.

    Science.gov (United States)

    Farid, Ayman Samir; Honkawa, Kazuyuki; Fath, Eman Mohamed; Nonaka, Nariaki; Horii, Yoichiro

    2013-04-11

    Fatty liver is a major metabolic disorder in dairy cows and is believed to result in major economic losses in dairy farming due to decreased health status, reproductive performance and fertility. Currently, the definitive means for diagnosing fatty liver is determining the fat content of hepatic tissue by liver biopsy, which is an invasive and costly procedure, making it poorly suited to dairy farms. Therefore, the key aim of this study was to investigate the measurement of serum paraoxonase-1 (PON1), an enzyme exclusively synthesized by the liver, as a sensitive noninvasive biomarker for diagnosis of fatty liver in dairy cows. A comparative cohort study using serum specimens from Holstein-Friesian dairy cows (46 healthy and 46 fatty liver cases) was conducted. Serum PON1 (paraoxonase, lactonase and arylesterase) activity and other biochemical and hematological parameters were measured. We found that serum PON1 activity was lower (Pratio (+LR), negative likelihood ratio (-LR), diagnostic odd ratio (DOR) and overall diagnostic accuracy in diagnosing fatty liver. The present results indicate that addition of serum PON1 activity measurement to the biochemical profile could improve the diagnosis of fatty liver in dairy cows, which would have a considerable clinical impact and lead to greater profitability in the dairy industry.

  3. Obese Mice Fed a Diet Supplemented with Enzyme-Treated Wheat Bran Display Marked Shifts in the Liver Metabolome Concurrent with Altered Gut Bacteria

    DEFF Research Database (Denmark)

    Kieffer, Dorothy A.; Piccolo, Brian D.; Marco, Maria L.

    2016-01-01

    ) associated with specific microbes may be involved. Objective: The objective of this study was to characterize ETWB-driven shifts in the cecal microbiome and to identify correlates between microbial changes and diet-related differences in liver metabolism in diet-induced obese mice that typically display......Background: Enzyme-treated wheat bran (ETWB) contains a fermentable dietary fiber previously shown to decrease liver triglycerides (TGs) and modify the gut microbiome in mice. It is not clear which mechanisms explain how ETWB feeding affects hepatic metabolism, but factors (i.e., xenometabolites...... steatosis. Methods: Five-week-old male C57BL/6J mice fed a 45%-lard based fat diet supplemented with ETWB (20% wt:wt) or rapidly digestible starch (control) (n = 15/group) for 10 wk were characterized by using a multi-omics approach. Multivariate statistical analysis was used to identify variables that were...

  4. Liver spots

    Science.gov (United States)

    ... skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun ...

  5. Analysis of risk factors for rebleeding after splenectomy and pericardial devascularization in treatment of portal hypertension due to liver cirrhosis

    Directory of Open Access Journals (Sweden)

    ZHANG Lei

    2015-03-01

    Full Text Available ObjectiveTo investigate the possible risk factors for rebleeding after splenectomy and pericardial devascularization in the treatment of portal hypertension due to liver cirrhosis, and to provide a certain basis for reducing the incidence of digestive tract re-hemorrhage for these patients. MethodsA retrospective analysis was performed on 238 cirrhotic patients with portal hypertension who underwent splenectomy and pericardial devascularization in the First Hospital of Lanzhou University from December 2003 to December 2013. These patients were divided into postoperative rebleeding group (n=32 and non-bleeding group (n=206. Univariate analysis (t test or chi-square test and multivariate logistic regression analysis were performed to investigate the risk factors for rebleeding after splenectomy and pericardial devascularization. ResultsOf the 32 patients with postoperative rebleeding, 17 had esophagogastric variceal bleeding, 11 had bleeding due to portal hypertensive gastropathy, and 4 had stress ulcer bleeding. The univariate analysis showed that there were significant differences between the two groups in the following factors: Child-Pugh classification of liver function, degree of liver cirrhosis evaluated intraoperatively, pathological changes of the gastric mucosa, platelet count, prothrombin time (PT, activated partial thromboplastin time (APTT, and presence of diabetes (all P<0.05. The multivariate logistic regression analysis suggested that the significant independent influential factors for postoperative rebleeding were presence of diabetes, Child-Pugh classification of liver function, degree of liver cirrhosis evaluated intraoperatively, diffuse lesion of the gastric mucosa, PT, and APTT. ConclusionFor cirrhotic patients with portal hypertension, the appropriate methods for managing these risk factors are of great clinical significance for preventing rebleeding after splenectomy and pericardial devascularization.

  6. Effect of hypoxia on the activity and binding of glycolytic and associated enzymes in sea scorpion tissues

    Directory of Open Access Journals (Sweden)

    Lushchak V.I.

    1998-01-01

    Full Text Available The effect of hypoxia on the levels of glycogen, glucose and lactate as well as the activities and binding of glycolytic and associated enzymes to subcellular structures was studied in brain, liver and white muscle of the teleost fish, Scorpaena porcus. Hypoxia exposure decreased glucose levels in liver from 2.53 to 1.70 µmol/g wet weight and in muscle led to its increase from 3.64 to 25.1 µmol/g wet weight. Maximal activities of several enzymes in brain were increased by hypoxia: hexokinase by 23%, phosphoglucoisomerase by 47% and phosphofructokinase (PFK by 56%. However, activities of other enzymes in brain as well as enzymes in liver and white muscle were largely unchanged or decreased during experimental hypoxia. Glycolytic enzymes in all three tissues were partitioned between soluble and particulate-bound forms. In several cases, the percentage of bound enzymes was reduced during hypoxia; bound aldolase in brain was reduced from 36.4 to 30.3% whereas glucose-6-phosphate dehydrogenase fell from 55.7 to 28.7% bound. In muscle PFK was reduced from 57.4 to 41.7% bound. Oppositely, the proportion of bound aldolase and triosephosphate isomerase increased in hypoxic muscle. Phosphoglucomutase did not appear to occur in a bound form in liver and bound phosphoglucomutase disappeared in muscle during hypoxia exposure. Anoxia exposure also led to the disappearance of bound fructose-1,6-bisphosphatase in liver, whereas a bound fraction of this enzyme appeared in white muscle of anoxic animals. The possible function of reversible binding of glycolytic enzymes to subcellular structures as a regulatory mechanism of carbohydrate metabolism is discussed.

  7. Reduction of Liver Span and Parameters of Inflammation in Nonalcoholic Fatty Liver Disease Patients Treated with Lycosome Formulation of Phosphatidylcholine: A Preliminary Report

    Directory of Open Access Journals (Sweden)

    Ivan M. Petyaev

    2018-01-01

    Full Text Available Twenty-nine newly diagnosed individuals with Nonalcoholic Fatty Liver Disease (NAFLD remaining on habitual dietary regimen were supplemented with regular or lycosome formulations of phosphatidylcholine (PC during a pilot, randomized, double-blinded clinical study. After two months of oral PC intake (450 mg daily the liver size as well as serum levels of hepatic enzymes and markers of inflammation were evaluated by ultrasonography and biochemical analysis. It was shown that there was a statistically significant reduction of medians for the Mid-Clavicular liver size from 16.0 cm (95/5% CI: 17.1/15.5 to 15.1 cm (95/5% CI: 17.2/14.4, P=0.021 in participants ingesting the lycosome-formulated PC (L-PC whereas regular formulation of PC (R-PC had only a marginal effect on this parameter (P=0.044. A similar tendency was observed in the Mid-Sternal liver size. Moreover, there was a reduction of medians for ALT values at the end point of the study (P=0.026 after ingestion of L-PC, while R-PC had no statistically significant effect. On the other hand, ingestion of both formulations was accompanied by reductions in values for Inflammatory Oxidative Damage (IOD and oxidized LDL in serum. However, L-PC had superior activity in these terms, presumably due to the presence of lycopene, a powerful antioxidant, in the L-PC-Lycosome structure. C-reactive protein level was moderately decreased (reduction of medians from 6.5 [95/5% CI: 7.7/5.8] mg/L to 5.1 [95/5% CI: 5.6/4.3] mg/L only after ingestion of L-PC. The greater efficacy of L-PC seen in NAFLD volunteers may reflect improved bioavailability of PC owing to better protection of the microencapsulated PC from gastrointestinal enzymes and possibly enhanced hepatic delivery of L-PC particles.

  8. Liver injury from Herbals and Dietary Supplements in the US Drug Induced Liver Injury Network

    Science.gov (United States)

    Navarro, Victor J.; Barnhart, Huiman; Bonkovsky, Herbert L.; Davern, Timothy; Fontana, Robert J.; Grant, Lafaine; Reddy, K. Rajender; Seeff, Leonard B.; Serrano, Jose; Sherker, Averell H.; Stolz, Andrew; Talwalkar, Jayant; Vega, Maricruz; Vuppalanchi, Raj

    2014-01-01

    Background The Drug-Induced Liver Injury Network (DILIN) studies hepatotoxicity due to conventional medications as well as herbals and dietary supplements (HDS). Rationale To characterize hepatotoxicity and its outcomes from HDS versus medications, patients with hepatotoxicity attributed to medications or HDS were enrolled prospectively between 2004 and 2013. The study took place among eight US referral centers that are part of the DILIN. Consecutive patients with liver injury referred to a DILIN center were eligible. The final sample comprised 130 (15.5%) of all subjects enrolled (839) who were judged to have experienced liver injury due to HDS. Hepatotoxicity due to HDS was evaluated by expert opinion. Demographic and clinical characteristics and outcome assessments including death and liver transplantation were ascertained. Cases were stratified and compared according to the type of agent implicated in liver injury; 45 had injury due to bodybuilding HDS, 85 due to non-bodybuilding HDS, and 709 due to medications. Main Results Liver injury due to HDS increased from 7% to 20% (p Bodybuilding HDS caused prolonged jaundice (median 91 days) in young men but did not result in any fatalities or liver transplantation. The remaining HDS cases presented as hepatocellular injury, predominantly in middle-aged women and more frequently led to death or transplantation compared to injury from medications (13% vs. 3%, p bodybuilding HDS is more severe than from bodybuilding HDS or medications, as evidenced by differences in unfavorable outcomes; death and transplantation. PMID:25043597

  9. Rapid release of tissue enzymes into blood after blast exposure: potential use as biological dosimeters.

    Directory of Open Access Journals (Sweden)

    Peethambaran Arun

    Full Text Available Explosive blast results in multiple organ injury and polytrauma, the intensity of which varies with the nature of the exposure, orientation, environment and individual resilience. Blast overpressure alone may not precisely indicate the level of body or brain injury after blast exposure. Assessment of the extent of body injury after blast exposure is important, since polytrauma and systemic factors significantly contribute to blast-induced traumatic brain injury. We evaluated the activity of plasma enzymes including aspartate aminotransferase (AST, alanine aminotransferase (ALT, lactate dehydrogenase (LDH and creatine kinase (CK at different time points after blast exposure using a mouse model of single and repeated blast exposures to assess the severity of injury. Our data show that activities of all the enzymes in the plasma were significantly increased as early as 1 h after blast exposure. The elevated enzyme activity remained up to 6 h in an overpressure dose-dependent manner and returned close to normal levels at 24 h. Head-only blast exposure with body protection showed no increase in the enzyme activities suggesting that brain injury alone does not contribute to the systemic increase. In contrast to plasma increase, AST, ALT and LDH activity in the liver and CK in the skeletal muscle showed drastic decrease at 6 h after blast exposures. Histopathology showed mild necrosis at 6 h and severe necrosis at 24 h after blast exposures in liver and no changes in the skeletal muscle suggesting that the enzyme release from the tissue to plasma is probably triggered by transient cell membrane disruption from shockwave and not due to necrosis. Overpressure dependent transient release of tissue enzymes and elevation in the plasma after blast exposure suggest that elevated enzyme activities in the blood can be potentially used as a biological dosimeter to assess the severity of blast injury.

  10. Liver-cell patterning lab chip: mimicking the morphology of liver lobule tissue.

    Science.gov (United States)

    Ho, Chen-Ta; Lin, Ruei-Zeng; Chen, Rong-Jhe; Chin, Chung-Kuang; Gong, Song-En; Chang, Hwan-You; Peng, Hwei-Ling; Hsu, Long; Yew, Tri-Rung; Chang, Shau-Feng; Liu, Cheng-Hsien

    2013-09-21

    A lobule-mimetic cell-patterning technique for on-chip reconstruction of centimetre-scale liver tissue of heterogeneous hepatic and endothelial cells via an enhanced field-induced dielectrophoresis (DEP) trap is demonstrated and reported. By mimicking the basic morphology of liver tissue, the classic hepatic lobule, the lobule-mimetic-stellate-electrodes array was designed for cell patterning. Through DEP manipulation, well-defined and enhanced spatial electric field gradients were created for in-parallel manipulation of massive individual cells. With this liver-cell patterning labchip design, the original randomly distributed hepatic and endothelial cells inside the microfluidic chamber can be manipulated separately and aligned into the desired pattern that mimicks the morphology of liver lobule tissue. Experimental results showed that both hepatic and endothelial cells were orderly guided, snared, and aligned along the field-induced orientation to form the lobule-mimetic pattern. About 95% cell viability of hepatic and endothelial cells was also observed after cell-patterning demonstration via a fluorescent assay technique. The liver function of CYP450-1A1 enzyme activity showed an 80% enhancement for our engineered liver tissue (HepG2+HUVECs) compared to the non-patterned pure HepG2 for two-day culturing.

  11. Gender and racial differences in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Pan, Jen-Jung; Fallon, Michael B

    2014-05-27

    Due to the worldwide epidemic of obesity, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of elevated liver enzymes. NAFLD represents a spectrum of liver injury ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) which may progress to advanced fibrosis and cirrhosis. Individuals with NAFLD, especially those with metabolic syndrome, have higher overall mortality, cardiovascular mortality, and liver-related mortality compared with the general population. According to the population-based studies, NAFLD and NASH are more prevalent in males and in Hispanics. Both the gender and racial ethnic differences in NAFLD and NASH are likely attributed to interaction between environmental, behavioral, and genetic factors. Using genome-wide association studies, several genetic variants have been identified to be associated with NAFLD/NASH. However, these variants account for only a small amount of variation in hepatic steatosis among ethnic groups and may serve as modifiers of the natural history of NAFLD. Alternatively, these variants may not be the causative variants but simply markers representing a larger body of genetic variations. In this article, we provide a concise review of the gender and racial differences in the prevalence of NAFLD and NASH in adults. We also discuss the possible mechanisms for these disparities.

  12. New therapeutic strategies for canine liver disease; Growth factors and liver progenitor cells

    NARCIS (Netherlands)

    Arends, B.

    2008-01-01

    The liver has the unique capacity to regulate its mass after loss of functional liver cells due to liver disease, injury, and/or toxicity. Unfortunately, in the course of chronic liver disease this meticulously regulated regeneration process is imbalanced resulting in a decreased regenerative

  13. Complement Receptors C5aR and C5L2 Are Associated with Metabolic Profile, Sex Hormones, and Liver Enzymes in Obese Women Pre- and Postbariatric Surgery

    Directory of Open Access Journals (Sweden)

    Reza Rezvani

    2014-01-01

    Full Text Available Objective. Obesity is associated with metabolic dysfunction with sex differences and chronic, low-grade inflammation. We proposed that hepatic expression of immune complement C3 related receptors (C3aR, C5aR, and C5L2 would be associated with pre- or postmenopausal status and metabolic profile in severely obese women. We hypothesized that C5L2/C5aR ratio, potentially influencing the ASP/C5L2 metabolic versus C5a/C5aR immune response, would predict metabolic profiles after weight loss surgery. Materials and Methods. Fasting plasma (hormone, lipid, and enzyme analysis and liver biopsies (RT-PCR gene expression were obtained from 91 women during surgery. Results. Hepatic C5L2 mRNA expression was elevated in pre- versus postmenopausal women (P<0.01 and correlated positively with circulating estradiol, estrone, ApoB, ApoA1, ApoA1/B, waist circumference, age, and LDL-C (all P<0.05. While plasma ASP was lower in pre- versus postmenopausal women (P<0.01, the hepatic C5L2/C5aR mRNA ratio was increased (P<0.001 and correlated positively with estrone (P<0.01 and estradiol (P<0.001 and negatively with circulating ApoB and liver enzymes ALT, AST, and GGT (all P<0.05. Over 12 months postoperatively, liver enzymes in low C5L2/C5aR mRNA ratio group remained higher (ALP and ALT, P<0.05, AST and GGT, P<0.001 2-way-ANOVA. Conclusion. C5L2-C5aR association with other mediators including estrogens may contribute to hepatic metabolic and inflammatory function.

  14. Defining normal liver stiffness range in a normal healthy Chinese population without liver disease.

    Directory of Open Access Journals (Sweden)

    James Fung

    Full Text Available BACKGROUND: For patients with chronic liver disease, different optimal liver stiffness cut-off values correspond to different stages of fibrosis, which are specific for the underlying liver disease and population. AIMS: To establish the normal ranges of liver stiffness in the healthy Chinese population without underlying liver disease. METHODS: This is a prospective cross sectional study of 2,528 healthy volunteers recruited from the general population and the Red Cross Transfusion Center in Hong Kong. All participants underwent a comprehensive questionnaire survey, measurement of weight, height, and blood pressure. Fasting liver function tests, glucose and cholesterol was performed. Abdominal ultrasound and transient elastography were performed on all participants. RESULTS: Of the 2,528 subjects, 1,998 were excluded with either abnormal liver parenchyma on ultrasound, chronic medical condition, abnormal blood tests including liver enzymes, fasting glucose, fasting cholesterol, high body mass index, high blood pressure, or invalid liver stiffness scan. The reference range for the 530 subjects without known liver disease was 2.3 to 5.9 kPa (mean 4.1, SD 0.89. The median liver stiffness was higher in males compared with females (4.3 vs 4.0 kPa respectively, p55 years (p=0.001. CONCLUSIONS: The healthy reference range for liver stiffness in the Chinese population is 2.3 to 5.9 kPa. Female gender and older age group was associated with a lower median liver stiffness.

  15. Tests of intestinal absorption of 3H labelled enzymes (wobenzym)

    International Nuclear Information System (INIS)

    Steffen, C.; Menzel, J.; Smolen, J.

    1979-01-01

    0.2 g of an enzyme mixture (Wobenzym) labelled with 3 H-acetic anhydride, were given orally to guinea pigs, which were arranged in 4 groups of 5 animals. The animals of each group were sacrificed at intervals of 30 minutes, 2, 4 and 24 hours after application. Radioactivity of the small and large intestine, plasma, urine, liver, heart, kidney, and skeletal muscle were determined. It could be shown that the labelled mixture of enzymes was absorbed from the intestine and was demonstrable in significant amounts in plasma, urine, heart, kidney, liver and skeletal muscle. (author)

  16. Syncytial giant-cell hepatitis due to autoimmune hepatitis type II (LKM1+) presenting as subfulminant hepatitis.

    Science.gov (United States)

    Ben-Ari, Z; Broida, E; Monselise, Y; Kazatsker, A; Baruch, J; Pappo, O; Skappa, E; Tur-Kaspa, R

    2000-03-01

    Giant cell hepatitis (GCH) in adults is a rare event. The diagnosis of GCH is based on findings of syncytial giant hepatocytes. It is commonly associated with either viral infection or autoimmune hepatitis type I. A patient with GCH due to autoimmune hepatitis type II (LKM1+) is described, a combination that has not been previously reported. Corticosteroid therapy was effective in decreasing serum liver enzymes; however, the patient deteriorated rapidly and developed subfulminant hepatic failure. Although an emergency orthotopic liver transplantation was performed, the patient died because of reperfusion injury. Interestingly, only a few giant hepatocytes were noted in the explanted liver. This case stresses the association of GCH with autoimmune disorders, the possible immune mechanism involved in the formation of giant cell hepatocytes, and illustrates the rapidly progressive course and unfavorable prognosis that these patients can develop.

  17. Mechanistic and quantitative aspects of liver tumour promotion in mice

    NARCIS (Netherlands)

    Ravenzwaay, van B.

    1988-01-01

    A variety of xenobiotic compounds is known to induce characteristic changes in the livers of laboratory animals. These changes include enlargement of the liver, usually as a result of cell enlargement (hypertrophy) or Increased cell replication (hyperplasia), induction of drugmetabolizing enzymes

  18. Resveratrol Ameliorates Experimental Alcoholic Liver Disease by Modulating Oxidative Stress

    Directory of Open Access Journals (Sweden)

    He Peiyuan

    2017-01-01

    Full Text Available The aim of this study was to investigate the hepatoprotective effects of resveratrol in alcoholic liver disease (ALD. Alcohol was administered to healthy female rats starting from 6% (v/v and gradually increased to 20% (v/v by the fifth week. After 16 weeks of intervention, liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] were analyzed using a chemistry analyzer, while hepatic antioxidant enzymes, oxidative stress markers, and caspase 3 activity were assessed using ELISA kits. Furthermore, hepatic CYP2E1 protein levels and mRNA levels of antioxidant and inflammation-related genes were determined using western blotting and RT-PCR, respectively. The results showed that resveratrol significantly attenuated alcohol-induced elevation of liver enzymes and improved hepatic antioxidant enzymes. Resveratrol also attenuated alcohol-induced CYP2E1 increase, oxidative stress, and apoptosis (caspase 3 activity. Moreover, genes associated with oxidative stress and inflammation were regulated by resveratrol supplementation. Taken together, the results suggested that resveratrol alleviated ALD through regulation of oxidative stress, apoptosis, and inflammation, which was mediated at the transcriptional level. The data suggests that resveratrol is a promising natural therapeutic agent against chronic ALD.

  19. Curcumin Attenuates N-Nitrosodiethylamine-Induced Liver Injury in Mice by Utilizing the Method of Metabonomics.

    Science.gov (United States)

    Qiu, Peiyu; Sun, Jiachen; Man, Shuli; Yang, He; Ma, Long; Yu, Peng; Gao, Wenyuan

    2017-03-08

    N-Nitrosodiethylamine (DEN) exists as a food additive in cheddar cheese, processed meats, beer, water, and so forth. It is a potent hepatocarcinogen in animals and humans. Curcumin as a natural dietary compound decreased DEN-induced hepatocarcinogenesis in this research. According to the histopathological examination of liver tissues and biomarker detection in serum and livers, it was demonstrated that curcumin attenuated DEN-induced hepatocarcinogenesis through parts of regulating the oxidant stress enzymes (T-SOD and CAT), liver function (ALT and AST) and LDHA, AFP level, and COX-2/PGE2 pathway. Furthermore, curcumin attenuated metabolic disorders via increasing concentration of glucose and fructose, and decreasing levels of glycine and proline, and mRNA expression of GLUT1, PKM and FASN. Docking study indicated that curcumin presented strong affinity with key metabolism enzymes such as GLUT1, PKM, FASN and LDHA. There were a number of amino acid residues involved in curcumin-targeting enzymes of hydrogen bonds and hydrophobic interactions. All in all, curcumin exhibited a potent liver protective agent inhibiting chemically induced liver injury through suppressing liver cellular metabolism in the prospective application.

  20. Enzyme activity deviates due to spatial and temporal temperature profiles in commercial microtiter plate readers.

    Science.gov (United States)

    Grosch, Jan-Hendrik; Sieben, Michaela; Lattermann, Clemens; Kauffmann, Kira; Büchs, Jochen; Spieß, Antje C

    2016-03-01

    Microtiter plates (MTP) and automatized techniques are increasingly applied in the field of biotechnology. However, the susceptibility of MTPs to edge effects such as thermal gradients can lead to high variation of measured enzyme activities. In an effort to enhance experimental reliability, to quantify, and to minimize instrument-caused deviations in enzyme kinetics between two MTP-readers, we comprehensively quantified temperature distribution in 96-well MTPs. We demonstrated the robust application of the absorbance dye cresol red as easily applicable temperature indicator in cuvettes and MTPs and determined its accuracy to ±0.16°C. We then quantified temperature distributions in 96-well MTPs revealing temperature deviations over single MTP of up to 2.2°C and different patterns in two commercial devices (BioTek Synergy 4 and Synergy Mx). The obtained liquid temperature was shown to be substantially controlled by evaporation. The temperature-induced enzyme activity variation within MTPs amounted to about 20 %. Activity deviations between MTPs and to those in cuvettes were determined to 40 % due to deviations from the set temperature in MTPs. In conclusion, we propose a better control of experimental conditions in MTPs or alternative experimental systems for reliable determination of kinetic parameters for bioprocess development. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Analysis of hepatic gene expression during fatty liver change due to chronic ethanol administration in mice

    International Nuclear Information System (INIS)

    Yin, H.-Q.; Je, Young-Tae; Kim, Mingoo; Kim, Ju-Han; Kong, Gu; Kang, Kyung-Sun; Kim, Hyung-Lae; Yoon, Byung-IL; Lee, Mi-Ock; Lee, Byung-Hoon

    2009-01-01

    Chronic consumption of ethanol can cause cumulative liver damage that can ultimately lead to cirrhosis. To explore the mechanisms of alcoholic steatosis, we investigated the global intrahepatic gene expression profiles of livers from mice administered alcohol. Ethanol was administered by feeding the standard Lieber-DeCarli diet, of which 36% (high dose) and 3.6% (low dose) of the total calories were supplied from ethanol for 1, 2, or 4 weeks. Histopathological evaluation of the liver samples revealed fatty changes and punctate necrosis in the high-dose group and ballooning degeneration in the low-dose group. In total, 292 genes were identified as ethanol responsive, and several of these differed significantly in expression compared to those of control mice (two-way ANOVA; p < 0.05). Specifically, the expression levels of genes involved in hepatic lipid transport and metabolism were examined. An overall net increase in gene expression was observed for genes involved in (i) glucose transport and glycolysis, (ii) fatty acid influx and de novo synthesis, (iii) fatty acid esterification to triglycerides, and (iv) cholesterol transport, de novo cholesterol synthesis, and bile acid synthesis. Collectively, these data provide useful information concerning the global gene expression changes that occur due to alcohol intake and provide important insights into the comprehensive mechanisms of chronic alcoholic steatosis

  2. EFFECTS OF RESVERATROL ON LIVER FUNCTION OF OBESE FEMALE WISTAR RATS

    Directory of Open Access Journals (Sweden)

    Nádia Araújo Miguel

    2016-07-01

    Full Text Available Resveratrol has antioxidant, anti-inflammatory, lipolytic, and antifibrotic properties, which may be useful in supplementation of obese patients and with liver problems. This study evaluated the effects of 6-week resveratrol supplementation on the lipid profile and liver function of female Wistar rats fed a high-fat diet to induce obesity. Sixty-four Wistar rats were divided into 4 groups (n = 16: the control group (C; the control obese group (CO; the resveratrol group (R; and the resveratrol obese group (RO. At the end of the experiment, the animals were anesthetized for blood collection and subsequent euthanasia for collection of liver biopsy. The parameters for body weight, liver weight, retroperitoneal fat weight, serum lipid and liver profiles and histopathological analysis were evaluated. The 6-week resveratrol administration did not induce weight loss nor did it reduce the lipid profile; however, it decreased the liver enzymes aspartate aminotransferase (AST and alkaline phosphatase (ALP and reduced the incidence of steatosis (75.0% in group RO compared with group CO (81.2%. Thus, we concluded that resveratrol supplementation for the short period of six weeks had a beneficial effect on liver function by reducing hepatic steatosis and the liver enzymes AST and ALP in obese female rats. Keywords: liver function; obesity; rats; resveratrol.

  3. Stability of Enzymes in Granular Enzyme Products for Laundry Detergents

    DEFF Research Database (Denmark)

    Biran, Suzan; Bach, Poul; Simonsen, Ole

    Enzymes have long been of interest to the detergent industry due to their ability to improve the cleaning efficiency of synthetic detergents, contribute to shortening washing times, and reduce energy and water consumption, provision of environmentally friendlier wash water effluents and fabric care....... However, incorporating enzymes in detergent formulations gives rise to numerous practical problems due to their incompatibility with and stability against various detergent components. In powdered detergent formulations, these issues can be partly overcome by physically isolating the enzymes in separate...... particles. However, enzymes may loose a significant part of their activity over a time period of several weeks. Possible causes of inactivation of enzymes in a granule may be related to the release of hydrogen peroxide from the bleaching chemicals in a moisture-containing atmosphere, humidity, autolysis...

  4. Injury due to thorotrast

    International Nuclear Information System (INIS)

    Mori, Takesaburo

    1976-01-01

    A synthetic study was performed on some of those to whom Thorotrast had been injected, in Japan. In the epidemiological study of 147 war woundeds to whom Thorotrast had been injected, it was noted that the Thorotrast injection increased the mortality rate and the incidences of malignant hepatic tumor, liver cirrhosis, and hematological diseases. Clinical study of 44 of them showed that the Thorotrast injection resulted in liver and hematopoietic hypofunctions. Analysis of the dissection of the injected area in 118 cases showed malignant hepatic tumor in 63.5%, liver cirrhosis in 14.4% and hematological diseases in 10.2%. The total of the three types of disease was 88.1%. Histological classification showed that of the malignant hepatic tumors due to Thorotrast, hepatobiliary cancer and hemangioendothelioma of the liver were frequent. By the comparison of the absorbed dose in the liver of the malignant hepatic tumors due to Thorotrast with that of the cancers developed in animal experiments, it was noted that the carcinogenic dose was a mean of 2,000 - 3,000 rad by accumulated dose. It was elucidated that carcinogenesis and fibrination were primary in injury due to Thorotrast, i.e., late injury due to Thorotrast, and that the increase in the accumulated dose in rogans and the increase of the local dose due to the gigantic growth of Thorotrast granules in organs greatly influenced carninogenesis and fibrination. (Chiba, N.)

  5. RESEARCH ARTICLES The spectrum of liver diseases in HIV ...

    African Journals Online (AJOL)

    Harriet

    Conclusion:Drug history, liver enzyme studies, ultrasound, and hepatitis B and C investigations identified the probable etiology in 60. (78%) of 77 patients with HIV infection presenting with symptoms and/or signs of liver disease. African Health Sciences 2008; 8(1): 8-12. Corresponding author: Ponsiano Ocama. Infectious ...

  6. Evaluation of liver function tests of HIV positive patients on ...

    African Journals Online (AJOL)

    Liver enzymes-alanine and aspartate aminotransferases and alkaline phosphatase (AST, ALT and ALP), bilirubin and serum proteins were determined using standard laboratory methods and these parameters were used to evaluate the liver function of human immunodeficiency virus (HIV)- positive patients receiving ...

  7. Integrated use of antioxidant enzymes and oxidative damage in two fish species to assess pollution in man-made hydroelectric reservoirs.

    Science.gov (United States)

    Sakuragui, M M; Paulino, M G; Pereira, C D S; Carvalho, C S; Sadauskas-Henrique, H; Fernandes, M N

    2013-07-01

    This study investigated the relationship between contaminant body burden and the oxidative stress status of the gills and livers of two wild fish species in the Furnas Hydroelectric Power Station (HPS) reservoir (Minas Gerais, Brazil). Gills and livers presented similar pathways of metals and organochlorine bioaccumulation. During June, organochlorines were associated with lipid peroxidation (LPO), indicating oxidative stress due to the inhibition of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. In the most polluted areas, metal concentrations in the liver were associated with metallothionein. During December, contaminants in the gills and liver were associated with catalase activity and LPO. Aldrin/dieldrin was the contaminant most associated with oxidative damage in the livers of both species. This integrated approach shed light on the relationship between adverse biological effects and bioaccumulation of contaminants inputted by intensive agricultural practices and proved to be a suitable tool for assessing the environmental quality of man-made reservoirs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Activity of certain enzymes in cadmium-poisoned chicks

    Energy Technology Data Exchange (ETDEWEB)

    Kench, J E; Gubb, P J.D.

    1970-01-01

    Activities of a number of enzymes in the liver and other tissues of newly hatched cadmium poisoned chicks have been compared with those of normal controls before and after incubation with Cd/sup +2/ at a concentration similar to that present in vivo. Concentrations of Cd/sup +2/ in the various cellular fractions were determined, after wet oxidation, by atomic absorption spectrophotometry. Interaction of Cd/sup +2/ with enzymes may provide information on the localization of enzymes within mitochondria and other cellular structures. 7 references.

  9. Referral patterns of patients with liver metastases due to colorectal cancer for resection.

    LENUS (Irish Health Repository)

    Al-Sahaf, O

    2012-02-01

    INTRODUCTION: Colorectal carcinoma accounts for 10% of cancer deaths in the Western World, with the liver being the most common site of distant metastases. Resection of liver metastases is the treatment of choice, with a 5-year survival rate of 35%. However, only 5-10% of patients are suitable for resection at presentation. AIMS: To examine the referral pattern of patients with liver metastases to a specialist hepatic unit for resection. METHODOLOGY: Retrospective review of patient\\'s charts diagnosed with colorectal liver metastases over a 10-year period. RESULTS: One hundred nine (38 women, 71 men) patients with liver metastases were included, mean age 61 years; 79 and 30 patients had synchronous and metachronus metastases, respectively. Ten criteria for referral were identified; the referral rate was 8.25%, with a resection rate of 0.9%. Forty two percent of the patients had palliative chemotherapy; 42% had symptomatic treatment. CONCLUSION: This study highlights the advanced stage of colorectal cancer at presentation; in light of modern evidence-based, centre-oriented therapy of liver metastasis, we conclude that criteria of referral for resection should be based on the availability of treatment modalities.

  10. [Liver trauma due to penetrating lesions: miscellanea, personal case series, clinical and CT findings].

    Science.gov (United States)

    Salzano, A; Nocera, V; De Rosa, A; Rossi, E; Carbone, M; Gatta, G; Vitale, L; Vigliotti, A

    2000-12-01

    Penetrating liver wounds are related to many causes and rank second after blunt abdominal and liver trauma. We will report the clinical and radiological findings of our personal series of patients with penetrating trauma, especially by firearms and stab and cut wounds. We will also try to define the diagnostic workup of these traumas, which is especially based on CT signs of liver damage and associated changes and which is of basic importance for following treatment, both surgical or conservative. In the last seven years we retrospectively reviewed 31 cases of penetrating liver trauma. The patients were 19 men and 12 women, ranging in age 18 to 73 (mean 42), with penetrating liver injuries from firearms (16 patients) and stab (9 cases) wounds; 6 patients had injuries from different causes. Abdominal CT was carried out in emergency with the CT Angiography (CTA) technique in all patients. In the patients with suspected chest and abdomen involvement CT was performed from the mid-chest for accurate assessment of diaphragm and lung bases and to exclude associated pleuropulmonary damage. Penetrating liver wounds were caused by firearms in 70% of cases, by stabbing in 12% and, in the extant 18%, by other causes such as home accidents, road and work traumas, and liver biopsy. In our series, the liver was most frequently involved, especially by firearms wounds; in our 16 cases the most frequent injuries were hemorrhagic tears. We found bullets in the liver in 6 cases. In one case of home accident the patient wounded himself while slicing bread with a long knife, which cut into the anterior abdominal wall and tore the anterior liver capsule, as seen at CTA. Penetrating wounds to liver and abdomen are less frequent than those to the chest. In the past decade the use of CT has changed the diagnostic and therapeutic approach to such injuries completely, decreasing the resort to explorative laparotomy and hepatorrhaphy. Indeed, CT provides a clear picture of the extent and

  11. Regulation of N-nitrosodimethylamine demethylase in rat liver and kidney.

    Science.gov (United States)

    Hong, J Y; Pan, J M; Dong, Z G; Ning, S M; Yang, C S

    1987-11-15

    In previous work, the low Km form of N-nitrosodimethylamine (NDMA) demethylase has been demonstrated to be due to a specific form of cytochrome P-450 (designated as P-450ac) and to be the enzyme required for the metabolic activation of NDMA. The present work deals with the regulation of P-450ac in rat liver during development as well as the mechanism of induction of P-450ac in rat liver and kidney by inducers. NDMA demethylase activity was almost undetectable in the liver of newborn rats, increased after day 4, and remained elevated throughout the first 17 days of the neonatal period. The enhancement of NDMA demethylase activity during development was accompanied by corresponding increases of P-450ac content and P-450ac mRNA levels as determined by Western and slot blot analyses, respectively. No sex differences with respect to this enzyme were observed in the developing rats. Acetone treatment on late-term pregnant rats for 2 days resulted in transplacental inductions of P-450ac and P-450ac mRNA in the newborn rats. Pretreatment of young male rats and adult female rats with acetone or isopropyl alcohol caused increases of NDMA demethylase activity and P-450ac content in the liver but no significant change in the P-450ac mRNA level. These facts suggest the possible existence of a posttranscription regulatory mechanism under these induction conditions. The presence of P-450ac in rat kidney was demonstrated by Western and Northern blot analyses. The renal form of P-450ac seemed to be regulated in a fashion similar to the hepatic P-450ac regarding its response to inducing factors such as fasting and acetone treatment.

  12. Hepatoprotective Effects of Chinese Medicine Herbs Decoction on Liver Cirrhosis in Rats

    Directory of Open Access Journals (Sweden)

    Nor Aziyah Mat-Rahim

    2017-01-01

    Full Text Available Hepatoprotective and curative activities of aqueous extract of decoction containing 10 Chinese medicinal herbs (HPE-XA-08 were evaluated in Sprague–Dawley albino rats with liver damage induced by thioacetamide (TAA. These activities were assessed by investigating the liver enzymes level and also histopathology investigation. Increases in alkaline phosphatase (ALP and gamma-glutamyl transferase (GGT levels were observed in rats with cirrhotic liver. No significant alterations of the liver enzymes were observed following treatment with HPE-XA-08. Histopathology examination of rats treated with HPE-XA-08 at 250 mg/kg body weight, however, exhibited moderate liver protective effects. Reduced extracellular matrix (ECM proteins within the hepatocytes were noted in comparison to the cirrhotic liver. The curative effects of HPE-XA-08 were observed with marked decrease in the level of ALP (more than 3x and level of GGT (more than 2x in cirrhotic rat treated with 600 mg/kg body weight HPE-XA-08 in comparison to cirrhotic rat treated with just water diluent. Reversion of cirrhotic liver to normal liver condition in rats treated with HPE-XA-08 was observed. Results from the present study suggest that HPE-XA-08 treatment assisted in the protection from liver cirrhosis and improved the recovery of cirrhotic liver.

  13. Demonstration of glucose-6-phosphate dehydrogenase in rat Kupffer cells by a newly-developed ultrastructural enzyme-cytochemistry

    Directory of Open Access Journals (Sweden)

    S Matsubara

    2009-06-01

    Full Text Available Although various tissue macrophages possess high glucose- 6-phosphate dehydrogenase (G6PD activity, which is reported to be closely associated with their phagocytotic/bactericidal function, the fine subcellular localization of this enzyme in liver resident macrophages (Kupffer cells has not been determined.We have investigated the subcellular localization of G6PD in Kupffer cells in rat liver, using a newly developed enzyme-cytochemical (copper-ferrocyanide method. Electron-dense precipitates indicating G6PD activity were clearly visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of Kupffer cells. Cytochemical controls ensured specific detection of the enzymatic activity. Rat Kupffer cells abundantly possessed enzyme-cytochemically detectable G6PD activity. Kupffer cell G6PD may play a role in liver defense by delivering NADPH to NADPH-dependent enzymes. G6PD enzyme-cytochemistry may be a useful tool for the study of Kupffer cell functions.

  14. CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems.

    Science.gov (United States)

    Wu, Zhexue; Lee, Doohyun; Joo, Jeongmin; Shin, Jung-Hoon; Kang, Wonku; Oh, Sangtaek; Lee, Do Yup; Lee, Su-Jun; Yea, Sung Su; Lee, Hye Suk; Lee, Taeho; Liu, Kwang-Hyeon

    2013-11-01

    Albendazole and fenbendazole are broad-spectrum anthelmintics that undergo extensive metabolism to form hydroxyl and sulfoxide metabolites. Although CYP3A and flavin-containing monooxygenase have been implicated in sulfoxide metabolite formation, the enzymes responsible for hydroxyl metabolite formation have not been identified. In this study, we used human liver microsomes and recombinant cytochrome P450s (P450s) to characterize the enzymes involved in the formation of hydroxyalbendazole and hydroxyfenbendazole from albendazole and fenbendazole, respectively. Of the 10 recombinant P450s, CYP2J2 and/or CYP2C19 was the predominant enzyme catalyzing the hydroxylation of albendazole and fenbendazole. Albendazole hydroxylation to hydroxyalbendazole is primarily mediated by CYP2J2 (0.34 μl/min/pmol P450, which is a rate 3.9- and 8.1-fold higher than the rates for CYP2C19 and CYP2E1, respectively), whereas CYP2C19 and CYP2J2 contributed to the formation of hydroxyfenbendazole from fenbendazole (2.68 and 1.94 μl/min/pmol P450 for CYP2C19 and CYP2J2, respectively, which are rates 11.7- and 8.4-fold higher than the rate for CYP2D6). Correlation analysis between the known P450 enzyme activities and the rate of hydroxyalbendazole and hydroxyfenbendazole formation in samples from 14 human liver microsomes showed that albendazole hydroxylation correlates with CYP2J2 activity and fenbendazole hydroxylation correlates with CYP2C19 and CYP2J2 activities. These findings were supported by a P450 isoform-selective inhibition study in human liver microsomes. In conclusion, our data for the first time suggest that albendazole hydroxylation is primarily catalyzed by CYP2J2, whereas fenbendazole hydroxylation is preferentially catalyzed by CYP2C19 and CYP2J2. The present data will be useful in understanding the pharmacokinetics and drug interactions of albendazole and fenbendazole in vivo.

  15. Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin-B1 Induced Hepatocellular Carcinoma in Rats

    Science.gov (United States)

    Maurya, Brajesh Kumar; Trigun, Surendra Kumar

    2016-01-01

    Fisetin, a known antioxidant, has been found to be cytotoxic against certain cell lines. However, the mechanism by which it inhibits tumor growth in vivo remains unexplored. Recently, we have demonstrated that Aflatoxin-B1 (AFB1) induced hepatocarcinogenesis is associated with activation of oxidative stress-inflammatory pathway in rat liver. The present paper describes the effect of in vivo treatment with 20 mg/kg b.w. Fisetin on antioxidant enzymes vis-a-vis oxidative stress level and on the profile of certain proinflammatory cytokines in the hepatocellular carcinoma (HCC) induced by two doses of 1 mg/kg b.w. AFB1 i.p. in rats. The reduced levels of most of the antioxidant enzymes, coinciding with the enhanced level of reactive oxygen species in the HCC liver, were observed to regain their normal profiles due to Fisetin treatment. Also, Fisetin treatment could normalize the enhanced expression of TNFα and IL1α, the two proinflammatory cytokines, reported to be involved in HCC pathogenesis. These observations were consistent with the regression of neoplastic lesion and declined GST-pi (placental type glutathione-S-transferase) level, a HCC marker, in the liver of the Fisetin treated HCC rats. The findings suggest that Fisetin attenuates oxidative stress-inflammatory pathway of AFB1 induced hepatocarcinogenesis. PMID:26682000

  16. Uridine prevents fenofibrate-induced fatty liver.

    Directory of Open Access Journals (Sweden)

    Thuc T Le

    Full Text Available Uridine, a pyrimidine nucleoside, can modulate liver lipid metabolism although its specific acting targets have not been identified. Using mice with fenofibrate-induced fatty liver as a model system, the effects of uridine on liver lipid metabolism are examined. At a daily dosage of 400 mg/kg, fenofibrate treatment causes reduction of liver NAD(+/NADH ratio, induces hyper-acetylation of peroxisomal bifunctional enzyme (ECHD and acyl-CoA oxidase 1 (ACOX1, and induces excessive accumulation of long chain fatty acids (LCFA and very long chain fatty acids (VLCFA. Uridine co-administration at a daily dosage of 400 mg/kg raises NAD(+/NADH ratio, inhibits fenofibrate-induced hyper-acetylation of ECHD, ACOX1, and reduces accumulation of LCFA and VLCFA. Our data indicates a therapeutic potential for uridine co-administration to prevent fenofibrate-induced fatty liver.

  17. Ophthalmic manifestations of 107 cases with hemolysis, elevated liver enzymes and low platelet count syndrome

    International Nuclear Information System (INIS)

    Erbagci, I.; Okumus, S.; Bekir, Necdet A.; Karaca, M.; Ugur, Mete G.

    2008-01-01

    Objective was to present various ophthalmologic disorders in a clinical series of hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome cases. This is a prospective clinical study performed between 2002 and 2005. One hundred seven HELLP attended in either Departments of Ophthalmology or Obstetrics and Gynecology, Medical School, Gaziantep University, Gaziantep, Turkey were evaluated. Mean age was 25.5 (22-36 years). Mean levels were 2.5 gravidity, 1.3 parity, 55,200/mm3 platelet counts, 308.7 U/I aspartate transaminase, 255.4 U/I alanine transminase and 1711.6U/I lactate dehydrogenase. Four patients died (3.7%) despite the proper treatments. Cortical blindness was observed in 3 cases (2.7%), serous retinal detachments in 4 (3.7%) and mild hypertension changes in 18 (16%). Ophthalmic complications are possible during and after this syndrome. Almost all ophthalmologic changes recover after delivery by cesarean section, nevertheless, it is essential that ophthalmologists should be aware of retinal disorders when this fatal complication of pregnancy is encountered. (author)

  18. Advances in sepsis-associated liver dysfunction

    Directory of Open Access Journals (Sweden)

    Dawei Wang

    2014-07-01

    Full Text Available Recent studies have revealed liver dysfunction as an early event in sepsis. Sepsis-associated liver dysfunction is mainly resulted from systemic or microcirculatory disturbances, spillovers of bacteria and endotoxin (lipopolysaccharide, LPS, and subsequent activation of inflammatory cytokines as well as mediators. Three main cell types of the liver which contribute to the hepatic response in sepsis are Kupffer cells (KCs, hepatocytes and liver sinusoidal endothelial cells (LSECs. In addition, activated neutrophils, which are also recruited to the liver and produce potentially destructive enzymes and oxygen-free radicals, may further enhance acute liver injury. The clinical manifestations of sepsis-associated liver dysfunction can roughly be divided into two categories: Hypoxic hepatitis and jaundice. The latter is much more frequent in the context of sepsis. Hepatic failure is traditionally considered as a late manifestation of sepsis-induced multiple organ dysfunction syndrome. To date, no specific therapeutics for sepsis-associated liver dysfunction are available. Treatment measure is mainly focused on eradication of the underlying infection and management for severe sepsis. A better understanding of the pathophysiology of liver response in sepsis may lead to further increase in survival rates.

  19. A Review of Liver Perfusion Method in Toxicology Studies

    Directory of Open Access Journals (Sweden)

    M karami

    2014-06-01

    Full Text Available Introduction: The isolated perfused rat liver is an accepted method in toxicology studies. The isolated perfused rat liver (IPRL is a useful experimental system for evaluating hepatic function without the influence of other organ systems, undefined plasma constituents, and neural-hormonal effects. Methods: The untreated male rats (180-220gr body weight were anesthetised with ether and then surgery with proper method. The abdomen was opened through a midline and one transversal incision and the bile duct was cannulated. Heparin sodium solution (0.5 ml; 500 U/ml in 0.9% NaCl was injected via the abdominal vena cava to prevent blood clotting. The liver inferior venacava was cannulated with PE-10 tubing and secured. The portal vein was immediately cannulated with an 23gr catheter which was secured and then liver was perfused in situ by Krebs- Henseleit buffer (pH 7.4; saturated with 95% O2 and 5% CO2; 37°C at a flow rate of 20 ml/min for 3hr. Temperature, perfusion pressure, flow rate and perfusion fluid pH were closely monitored during the perfusion. Results: Transferase enzymes (ALT, AST alterations can be widely used as a measure of biochemical alterations in order to assess liver damage due to use of drugs such as isoniazid (INH and animal and plant toxins. Accumulated material in gallbladder are valuable samples to assess the level of Glutathione (GSH. Sections of perfused liver tissue can also be effectively analyzed for pathological aspects such as necrosis, fibrosis, cellularity. Conclusion: The isolated perfused rat liver (IPRL is a useful and Sutible experimental system for evaluating hepatic function. In this system, the effects of adjacent organs, on the liver is minimized

  20. Butylated hydroxyanisole induces distinct expression patterns of Nrf2 and detoxification enzymes in the liver and small intestine of C57BL/6 mice

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Lin [Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058 (China); Department of Pharmacology, University of Nantong, Nantong (China); Chen, Yeru; Wu, Deqi; Shou, Jiafeng [Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058 (China); Wang, Shengcun [Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058 (China); Ye, Jie [Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058 (China); Tang, Xiuwen, E-mail: xiuwentang@zju.edu.cn [Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058 (China); Wang, Xiu Jun, E-mail: xjwang@zju.edu.cn [Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058 (China)

    2015-11-01

    Butylated hydroxyanisole (BHA) is widely used as an antioxidant and preservative in food, food packaging and medicines. Its chemopreventive properties are attributing to its ability to activate the transcription factor NF-E2 p45-related factor 2 (Nrf2), which directs central genetic programs of detoxification and protection against oxidative stress. This study was to investigate the histological changes of Nrf2 and its regulated phase II enzymes Nqo1, AKR1B8, and Ho-1 in wild-type (WT) and Nrf2{sup −/−} mice induced by BHA. The mice were given a 200 mg/kg oral dose of BHA daily for three days. Immunohistochemistry revealed that, in the liver from WT mice, BHA increased Nqo1 staining in hepatocytes, predominately in the pericentral region. In contrast, the induction of AKR1B8 appeared mostly in hepatocytes in the periportal region. The basal and inducible Ho-1 was located almost exclusively in Kupffer cells. In the small intestine from WT mice, the inducible expression patterns of Nqo1 and AKR1B8 were nearly identical to that of Nrf2, with more intense staining in the villus than that the crypt. Conversely, Keap1 was more highly expressed in the crypt, where the proliferative cells reside. Our study demonstrates that BHA elicited differential expression patterns of phase II-detoxifying enzymes in the liver and small intestine from WT but not Nrf2{sup −/−} mice, demonstrating a cell type specific response to BHA in vivo. - Highlights: • Histological view of basal and inducible Nrf2 and its targets in vivo • Induction of detoxification enzymes by BHA is cell-type dependent. • BHA induces the expression of HO-1 in Kupffer cells.

  1. Effect of halofantrine administration on some liver and heart ...

    African Journals Online (AJOL)

    The effect of halofantrine on liver and the heart was evaluated in 15 healthy adult human volunteers (11 females and 4 males), after a single oral dose of halofantrine given to each volunteer. Blood samples were collected at predetermined time intervals and analysed for the various liver and heart enzyme activities ...

  2. The Association between Fruit and Vegetable Intake and Liver ...

    African Journals Online (AJOL)

    BACKGROUND: Intake of fiber and antioxidants and following hypocaloric diets has beneficial effects on reduction of the liver enzymes. Fruits and vegetables are low in calorie and rich in fiber and antioxidants. There are few studies about special dietary effects on liver function. The aim of this study was to evaluate the ...

  3. [Hyperammonemia due to ornithine transcarbamylase deficiency--a cause of lethal metabolic crisis during the newborn period and infancy (author's transl)].

    Science.gov (United States)

    Schuchmann, L; Colombo, J P; Fischer, H

    1980-05-01

    A severe hyperammonemia is the characteristic finding in patients with enzyme defects in urea cycle and one of the main causes of the acute metabolic crisis dsuring the newborn period and infancy. A case report is given about two male infants, who died in the age of one and of seven months respectively. In the second child the blood ammonia concentration raised up to 833 micrograms/100 ml, and, OTC deficiency was diagnosed due to enzyme determination in liver biopsie. Probably, the first child, that also died as newborn, suffered from the same disease. In this case, only post mortem findings are available.

  4. Metabolism of ethylbenzene by human liver microsomes and recombinant human cytochrome P450s (CYP).

    Science.gov (United States)

    Sams, Craig; Loizou, George D; Cocker, John; Lennard, Martin S

    2004-03-07

    The enzyme kinetics of the initial hydroxylation of ethylbenzene to form 1-phenylethanol were determined in human liver microsomes. The individual cytochrome P450 (CYP) forms catalysing this reaction were identified using selective inhibitors and recombinant preparations of hepatic CYPs. Production of 1-phenylethanol in hepatic microsomes exhibited biphasic kinetics with a high affinity, low Km, component (mean Km = 8 microM; V(max) = 689 pmol/min/mg protein; n = 6 livers) and a low affinity, high Km, component (Km = 391 microM; V(max) = 3039 pmol/min/mg protein; n = 6). The high-affinity component was inhibited 79%-95% (mean 86%) by diethyldithiocarbamate, and recombinant CYP2E1 was shown to metabolise ethylbenzene with low Km (35 microM), but also low (max) (7 pmol/min/pmol P450), indicating that this isoform catalysed the high-affinity component. Recombinant CYP1A2 and CYP2B6 exhibited high V(max) (88 and 71 pmol/min/pmol P450, respectively) and high Km (502 and 219 microM, respectively), suggesting their involvement in catalysing the low-affinity component. This study has demonstrated that CYP2E1 is the major enzyme responsible for high-affinity side chain hydroxylation of ethylbenzene in human liver microsomes. Activity of this enzyme in the population is highly variable due to induction or inhibition by physiological factors, chemicals in the diet or some pharmaceuticals. This variability can be incorporated into the risk assessment process to improve the setting of occupational exposure limits and guidance values for biological monitoring.

  5. Effect of selective hepatic inflow occlusion during liver cancer resection on liver ischemia-reperfusion injury

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    Yin-Tian Deng

    2016-11-01

    Full Text Available Objective: To study the effect of selective hepatic inflow occlusion during liver cancer resection on liver ischemia-reperfusion injury. Methods: A total of 68 patients with primary liver cancer who underwent left liver resection in our hospital between May 2012 and August 2015 were selected for study and divided into group A (selective hepatic inflow occlusion of left liver and group B (Prignle hepatic inflow occlusion according to different intraoperative blood occlusion methods, serum was collected before and after operation to determine liver enzyme content, the removed liver tissue was collected to determine energy metabolism indexes, inflammation indexes and oxidative stress indexes. Results: 1 d, 3 d and 5 d after operation, GPT, GOT, GGT, LDH and ALP content in serum of both groups were significantly higher than those before operation, and GPT, GOT, GGT, LDH and ALP content in serum of group A 1 d, 3 d and 5 d after operation were significantly lower than those of group B; ATP, ADP, AMP, PI3K, AKT, GSK3β, T-AOC, PrxI and Trx content in liver tissue of group A were significantly higher than those of group B while PTEN, IL-12p40, MDA and MPO content were significantly lower than those of group B. Conclusions: Selective hepatic inflow occlusion during liver cancer resection can reduce the liver ischemia-reperfusion injury, improve the energy metabolism of liver cells and inhibit inflammation and oxidative stress in liver tissue.

  6. Fatty liver index and hepatic steatosis index for prediction of non-alcoholic fatty liver disease in type 1 diabetes.

    Science.gov (United States)

    Sviklāne, Laura; Olmane, Evija; Dzērve, Zane; Kupčs, Kārlis; Pīrāgs, Valdis; Sokolovska, Jeļizaveta

    2018-01-01

    Little is known about the diagnostic value of hepatic steatosis index (HSI) and fatty liver index (FLI), as well as their link to metabolic syndrome in type 1 diabetes mellitus. We have screened the effectiveness of FLI and HSI in an observational pilot study of 40 patients with type 1 diabetes. FLI and HSI were calculated for 201 patients with type 1 diabetes. Forty patients with FLI/HSI values corresponding to different risk of liver steatosis were invited for liver magnetic resonance study. In-phase/opposed-phase technique of magnetic resonance was used. Accuracy of indices was assessed from the area under the receiver operating characteristic curve. Twelve (30.0%) patients had liver steatosis. For FLI, sensitivity was 90%; specificity, 74%; positive likelihood ratio, 3.46; negative likelihood ratio, 0.14; positive predictive value, 0.64; and negative predictive value, 0.93. For HSI, sensitivity was 86%; specificity, 66%; positive likelihood ratio, 1.95; negative likelihood ratio, 0.21; positive predictive value, 0.50; and negative predictive value, 0.92. Area under the receiver operating characteristic curve for FLI was 0.86 (95% confidence interval [0.72; 0.99]); for HSI 0.75 [0.58; 0.91]. Liver fat correlated with liver enzymes, waist circumference, triglycerides, and C-reactive protein. FLI correlated with C-reactive protein, liver enzymes, and blood pressure. HSI correlated with waist circumference and C-reactive protein. FLI ≥ 60 and HSI ≥ 36 were significantly associated with metabolic syndrome and nephropathy. The tested indices, especially FLI, can serve as surrogate markers for liver fat content and metabolic syndrome in type 1 diabetes. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  7. Binding of Cimetidine to Balb/C Mouse Liver Catalase; Kinetics and Conformational Studies.

    Science.gov (United States)

    Jahangirvand, Mahboubeh; Minai-Tehrani, Dariush; Yazdi, Fatemeh; Minai-Tehrani, Arash; Razmi, Nematollah

    2016-01-01

    Catalase is responsible for converting hydrogen peroxide (H2O2) into water and oxygen in cells. This enzyme has high affinity for hydrogen peroxide and can protect the cells from oxidative stress damage. Catalase is a tetramer protein and each monomer contains a heme group. Cimetidine is a histamine H2 receptor blocker which inhibits acid release from stomach and is used for gasterointestinal diseases. In this research, effect of cimetidine on the activity of liver catalase was studied and the kinetic parameters of this enzyme and its conformational changes were investigated. Cell free extract of mouse liver was used for the catalase assay. The activity of the catalase was detected in the absence and presence of cimetidine by monitoring hydrogen peroxide reduction absorbance at 240 nm. The purified enzyme was used for conformational studies by Fluorescence spectrophotometry. The data showed that cimetidine could inhibit the enzyme in a non-competitive manner. Ki and IC50 values of the drug were determined to be about 0.75 and 0.85 uM, respectively. The Arrhenius plot showed that activation energy was 6.68 and 4.77 kJ/mol in the presence and absence of the drug, respectively. Fluorescence spectrophotometry revealed that the binding of cimetidine to the purified enzyme induced hyperchromicity and red shift which determined the conformational change on the enzyme. Cimetidine could non-competitively inhibit the liver catalase with high affinity. Binding of cimetidine to the enzyme induced conformational alteration in the enzyme.

  8. Changes at transcriptional level during liver regeneration in the rat

    International Nuclear Information System (INIS)

    Subba Rao, M.N.; Netrawali, M.S.; Pradhan, D.S.; Sreenivasan, A.

    1976-01-01

    A great upheaval in RNA synthetic pattern is known to occur during the early periods after partial hepatectomy. Such changes are being studied in regenerating rat liver with a view to understanding regulatory mechanisms of eukaryotic transcription. Follwoing partial hepatectomy, RNA synthesis is rat liver showed graded increase during 4 to 18 hours. At these time intervals, a significant enhancement could be discerned both in template efficiency of chromatin and in RNA polymerase activity in this tissue. Further examination revealed that the activity of RNA polymerase II (extra-nucleolar enzyme) stimulated to a much greater extent as compared to that of RNA polymerase I (nucleolar enzyme). Partial hepatectomy also resulted in significant alterations in turnovers of chromosomal acidic proteins in liver. 32 P-orthophosphate injected intraperitoneally was used in these studies. (author)

  9. Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver

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    Zeba Farooqui

    Full Text Available Cisplatin (CP is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies were attempted to prevent CP hepatotoxicity but were not found suitable for therapeutic application. Nigella sativa has been shown to prevent/reduce the progression of certain type of cardiovascular, kidney and liver diseases. Present study investigates whether N. sativa oil (NSO can prevent CP induced hepatotoxic effects. Rats were divided into four groups viz. control, CP, NSO and CPNSO. Animals in CPNSO and NSO group were administered NSO (2 ml/kg bwt, orally with or without single hepatotoxic dose of CP (6 mg/kg bwt, i.p. respectively. CP hepatotoxicity was recorded by increased serum ALT and AST activities. CP treatment caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation and decreased enzymatic and non-enzymatic antioxidants. Furthermore, the activities of various carbohydrate metabolism and membrane enzymes were altered by CP treatment. In contrast, NSO administration to CP treated rats, markedly ameliorated the CP elicited deleterious alterations in liver. Histopathological observations showed extensive liver damage in CP treated animals while greatly reduced tissue injury in CPNSO group. In conclusion, NSO appears to protect CP induced hepatotoxicity by improving energy metabolism and strengthening antioxidant defense mechanism. Keywords: Cisplatin, Nigella sativa oil, Carbohydrate metabolism, Antioxidant

  10. [A case of pulmonary tuberculosis complicated with an orthotopic liver transplantation].

    Science.gov (United States)

    Kamiya, Hiroyuki; Toyota, Emiko; Kobayashi, Nobuyuki; Kudo, Koichiro

    2006-04-01

    The infectious disease is one of the most important complications related to the organ transplantation. Patients using immunosuppressive agents often present atypical tuberculosis and the treatment of such case is far more difficult in some cases due to the liver damage and/or the drug interaction. We report a case of pulmonary tuberculosis in a patient of 60-year-old man using tacrolimus after an orthotopic liver transplantation. He had liver transplanted orthotopically for the long-term history of chronic hepatitis B and subsequent liver failure on January 28, 2004. An abnormal shadow was first detected on his chest X-ray film on October, 2004. He was admitted to our hospital after the smear of the gastric juice showed some acid-fast bacilli and tubercle bacilli were confirmed by polymerase chain reaction (PCR). Tuberculin skin test was positive (erythema 10 x 10) and the computed tomography (CT) scan of his chest revealed a nodular opacity with some smaller nodules scattered around in the right upper lobe. We started four anti-tuberculous drugs other than pyrazinamide (PZA) and rifampicin (RFP), which included isoniazid (INH), ethambutol (EB), streptomycin (SM), levofloxacin (LVFX). The liver enzyme was transiently elevated (AST 123 IU/I, ALT 103 IU/I) but improved after desensitization against INH. The blood concentration of tacrolimus preserved between 5 and 7 ng/ml and there was no need to change the dosage.

  11. The effects of hydroalcoholic extract of Portulaca Oleracea on the serum concentreation of Hepatic enzymes in Rats

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    Ali Zarei

    2014-11-01

    Full Text Available Background Hyperlipidemia can be cause a variety of diseases such as atherosclerosis, diabetes and fatty liver and subsequent liver enzyme increases. The Portulaca Oleracea plant has hypoglycemic and hypolipidemic properties. Therefore, in this study the effect of Portulca Oleracea herb extract on serum liver enzymes including aspartate aminotransferase (SGOT or AST, alanine aminotransferase (SGPT or ALT and alkaline phosphatase (ALP in rats were studied. Materials and Methods: In this experimental study, 60 Wistar rats were divided into 6 groups (n=10. Control group with normal diet, fat diet group and other groups, the experimental group received the same diet plus fat Portulaca oleracea extract maximum dose (800, the mean dose of (400, and a minimum dose of (200 mg / kg or intraperitoneally injection (ip and sort of Atorvastatin (10 mg kg. After the end of this period (21 days, blood sampling was performed and collected data were analyzed using the t and Tukey test, and SPSS software version 11.5. Results Comparison of statistical results indicated that alanine aminotransferase (ALT and Alkaline phosphatase (ALP increase in the control group that received only fatty foods, while the experimental groups received extract of Portulaca Oleracea, and groups receiving Atorvastatin had reduced levels of liver enzymes. Conclusion: Regarding hypoglycemic and hypolipidemic antioxidant activity of the extract and its effect on reducing liver enzymes, plant extracts can be recommended to improve liver function.

  12. Expression of genes for microRNA-processing enzymes is altered in advanced non-alcoholic fatty liver disease.

    Science.gov (United States)

    Sharma, Haveesh; Estep, Michael; Birerdinc, Aybike; Afendy, Arian; Moazzez, Amir; Elariny, Hazem; Goodman, Zachary; Chandhoke, Vikas; Baranova, Ancha; Younossi, Zobair M

    2013-08-01

    Recently, microRNAs (miRNA) have been linked to the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH). First transcribed as pri-miRNA, these molecules are further processed by a complex of endonuclear and cytosolic RNA binding molecules to form mature miRNAs. The aim of this study is to investigate mechanisms of miRNA regulation in the visceral adipose of obese NAFLD patients via measuring expression of miRNA processing enzymes and pri-miRNA. Total RNAs were extracted from visceral adipose tissue (VAT) samples collected from patients undergoing bariatric surgery. All patients had biopsy-proven NAFLD (NASH patients [n = 12] and non-NASH NAFLD [n = 12]). For each patient, we profiled mRNA levels for three miRNA processing elements (Drosha, DGCR8, and Dicer1) and seven pri-miRNAs (pri-miR-125b-2, pri-miR-16-2, pri-miR-26a-1, pri-miR-26a-2, pri-miR-7-1, pri-miR-7-2, and pri-miR-7-3). Expression of Dicer1, Drosha and DGCR8 was significantly increased within the NASH cohort along with expression of pri-miR-7-1. The presence of focal necrosis on the liver biopsy correlated significantly with levels of Dicer1 and DGRC8. Both NASH and ballooning degeneration of hepatocytes correlated negatively with the expression levels of hsa-miR-125b. Histologic NASH correlated positively with the expression levels of pri-miR-16-2 and pri-miR-7-1. The presence of the hepatocyte's ballooning degeneration in the liver biopsy correlated positively with pri-miR-26a-1 and pri-miR-7-1. The expression profile of pri-miR-125b-2 also correlated positively with body mass index. Our findings support the hypothesis that VAT-derived miRNA may contribute to the pathogenesis of NASH in obese patients. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  13. Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development

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    Leah Y. Liu

    2013-09-01

    Genome-wide association studies (GWAS have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10 decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50 decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes.

  14. Liver Enzymes and the Development of Posttransplantation Diabetes Mellitus in Renal Transplant Recipients

    NARCIS (Netherlands)

    Klaassen, Gerald; Corpeleijn, Eva; Deetman, Nicole P E; Navis, Gerjan J; Bakker, Stephan J L; Zelle, Dorien M

    BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is common in renal transplant recipients (RTR), increasing the risk of graft failure, cardiovascular disease, and mortality. Early detection of a high risk for PTDM is warranted. Because liver function and liver fat are involved, we

  15. Current status of prediction of drug disposition and toxicity in humans using chimeric mice with humanized liver.

    Science.gov (United States)

    Kitamura, Shigeyuki; Sugihara, Kazumi

    2014-01-01

    1. Human-chimeric mice with humanized liver have been constructed by transplantation of human hepatocytes into several types of mice having genetic modifications that injure endogenous liver cells. Here, we focus on liver urokinase-type plasminogen activator-transgenic severe combined immunodeficiency (uPA/SCID) mice, which are the most widely used human-chimeric mice. Studies so far indicate that drug metabolism, drug transport, pharmacological effects and toxicological action in these mice are broadly similar to those in humans. 2. Expression of various drug-metabolizing enzymes is known to be different between humans and rodents. However, the expression pattern of cytochrome P450, aldehyde oxidase and phase II enzymes in the liver of human-chimeric mice resembles that in humans, not that in the host mice. 3. Metabolism of various drugs, including S-warfarin, zaleplon, ibuprofen, naproxen, coumarin, troglitazone and midazolam, in human-chimeric mice is mediated by human drug-metabolizing enzymes, not by host mouse enzymes, and thus resembles that in humans. 4. Pharmacological and toxicological effects of various drugs in human-chimeric mice are also similar to those in humans. 5. The current consensus is that chimeric mice with humanized liver are useful to predict drug metabolism catalyzed by cytochrome P450, aldehyde oxidase and phase II enzymes in humans in vivo and in vitro. Some remaining issues are discussed in this review.

  16. Effects of extremely low frequency electromagnetic fields on liver enzymes in Guinea pig

    International Nuclear Information System (INIS)

    Zare, S.; Hayatgeiby, H.; Alivandy Farkhad, S.; Tagizadeh, A.

    2007-01-01

    Electromagnetic field has various effects on living organisms such as blood composition or enzymatic changes. The effects depend on the electromagnetic intensity and the time of exposure. This study has been carried out to measure the variations of liver enzymes SGOT and SGPT Levels in 36 adult male, Guinea Pigs, that have been divided into 6 groups. Group A, as the control, exposed to nil electromagnetic field for two hours per day for 5 days. Group B, exposed to 0.013 micro T in 5 Hz for the same period. Group C, exposed to 0.207 micro T in 50 Hz in the similar condition. Group D, exposed for' four hours per day for 5 days in 0.013 micro T in 5Hz. Group E, tested in 0.207 micro T in 50 Hz as the group D. Group F, used as the controlled group exposed for four hours per day in nil electromagnetic field. Blood of the Guinea pigs were analysed after 5 days. The results have shown significant differences among different groups, regarding the SCOT and SGPT when compared with those of the controlled group. Statistically, they are meaningful when measured by Dunnett test indicating a significant difference between the controlled group and the tested group, soas the SGOT and SGPT have decreased in both cases

  17. Zonulin level, a marker of intestinal permeability, is increased in association with liver enzymes in young adolescents.

    Science.gov (United States)

    Kim, Ji Hee; Heo, Ju Sun; Baek, Kyung Suk; Kim, Soo-Yeon; Kim, Jung Hyun; Baek, Kwang-Hyun; Kim, Ki Eun; Sheen, Youn Ho

    2018-06-01

    Zonulin is acknowledged as the only physiological mediator established to reversibly regulate intestinal permeability through modulation of intercellular tight junctions. We aimed to determine whether there are differences in zonulin levels between 74 subjects with overweight or obesity and 76 with normal-weight and to assess correlations of circulating zonulin levels with anthropometric measures and obesity-related biomarkers. We assessed anthropometric and laboratory measures, including body mass index (BMI) z-score, blood pressure, liver enzymes, lipid profiles, and insulin resistance. Serum zonulin levels were measured using an enzyme-linked immunosorbent assay. The mean age of the participants was 12.8 ± 1.5 years. Circulating serum zonulin levels were significantly increased in subjects with overweight/obesity compared with those of normal-weight (P = 0.03). Zonulin levels were significantly and positively associated with BMI z-score, alanine aminotransferase levels, triglyceride, fasting insulin, and insulin resistance as indicated by the homeostatic model assessment of insulin resistance (HOMA-IR) (all P zonulin levels in adolescents with overweight or obesity (P zonulin levels in this subgroup analysis (P = 0.06). Serum zonulin is a biomarker associated with hepatic metabolic disturbances in young adolescents with overweight or obesity. The positive relationship suggests a potentially relevant pathophysiological mechanism linking zonulin to hepatic metabolism in this age group of young adolescents with overweight or obesity. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Levosimendan: a cardiovascular drug to prevent liver ischemia-reperfusion injury?

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    Peter Onody

    Full Text Available INTRODUCTION: Temporary occlusion of the hepatoduodenal ligament leads to an ischemic-reperfusion (IR injury in the liver. Levosimendan is a new positive inotropic drug, which induces preconditioning-like adaptive mechanisms due to opening of mitochondrial KATP channels. The aim of this study was to examine possible protective effects of levosimendan in a rat model of hepatic IR injury. MATERIAL AND METHODS: Levosimendan was administered to male Wistar rats 1 hour (early pretreatment or 24 hours (late pretreatment before induction of 60-minute segmental liver ischemia. Microcirculation of the liver was monitored by laser Doppler flowmeter. After 24 hours of reperfusion, liver and blood samples were taken for histology, immuno- and enzyme-histochemistry (TUNEL; PARP; NADH-TR as well as for laboratory tests. Furthermore, liver antioxidant status was assessed and HSP72 expression was measured. RESULTS: In both groups pretreated with levosimendan, significantly better hepatic microcirculation was observed compared to respective IR control groups. Similarly, histological damage was also reduced after levosimendan administration. This observation was supported by significantly lower activities of serum ALT (p early = 0.02; p late = 0.005, AST (p early = 0.02; p late = 0.004 and less DNA damage by TUNEL test (p early = 0.05; p late = 0.034 and PAR positivity (p early = 0.02; p late = 0.04. Levosimendan pretreatment resulted in significant improvement of liver redox homeostasis. Further, significantly better mitochondrial function was detected in animals receiving late pretreatment. Finally, HSP72 expression was increased by IR injury, but it was not affected by levosimendan pretreatment. CONCLUSION: Levosimendan pretreatment can be hepatoprotective and it could be useful before extensive liver resection.

  19. Radiologic management of hepatic arterial stenosis or thrombosis following liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Byung Suck; Sung, Kyu Bo; Lim, Soo Mee; Yoon, Hyun Ki; Song, Ho Young [Asan Medical Center, Ulsan Univ. College of Medicine, Seoul (Korea, Republic of)

    2001-06-01

    To assess the results and usefulness of interventional procedures for hepatic arterial stenosis or thrombosis following liver transplantation. During the past five years, eight patients aged 1-59 (mean, 39) years among 187 liver transplant recipients showed elevated of liver enzyme levels (AST/ALT) and decreased arterial flow at Doppler ultrasound. Hepatic arteriography revealed luminal stenosis or occlusion at the proper hepatic artery, and six patients, one of whom required thrombolysis before the procedure, underwent percutaneous transluminal angioplasty (PTA) using a balloon. In two with thrombosis, thrombolysis without PTA was performed. In order to increase hepatic arterial flow, four patients underwent additional coil embolization of the gastroduodenal or splenic artery. Hepatic arterial flow recovered in all six patients after PTA. Three required repeat PTA for restenosis and one of these needed stent placement after repeated PTA. At follow-up, 6-17 months later, the three had good hepatic function. Within four days, the other three expired due to graft failure, hepatorenal syndrome and sepsis. One of the patients who underwent thrombolysis without PTA expired and the other required retransplantation. In this case there were no procedure - related complications. Radiologic interventions are useful for treatment of hepatic arterial stensis or thrombosis in patients with liver transplantations.

  20. [Lymphoplasmacytic inflammatory pseudotumor of the liver].

    Science.gov (United States)

    Valdivielso Córtazar, E; Yáñez López, J A; Yáñez Gónzalez-Dopeso, L; Diz-Lois Palomares, M; González Conde, B; Alonso Aguirre, P

    2016-01-01

    We present the case of a middle-aged woman with antecedents of cholecystectomy and several episodes of resi-dual coledocolitiasis resolved endoscopically. She attended Emergency Services due to a new clinical picture of abdo-minal pain and alteration of hepatic enzymes. Image tests showed lesions that suggested hepatic abscesses without ruling out a malign origin. Given this doubt it was decided to carry out a thick needle biopsy obtaining a diagnosis of an inflammatory pseudotumour of the liver related to IgG4-related disease. This is an infrequent entity but must be taken into consideration because - unlike malign pathology, which is the main differential diagnosis - its behaviour is benign, with a good evolution with medical treatment. That is why a suitable diagnosis is vital to avoid aggressive, diagnostic-therapeutic procedures.

  1. Zingiber officinale acts as a nutraceutical agent against liver fibrosis

    Science.gov (United States)

    2011-01-01

    Background/objective Zingiber officinale Roscoe (ginger) (Zingiberaceae) has been cultivated for thousands of years both as a spice and for medicinal purposes. Ginger rhizomes successive extracts (petroleum ether, chloroform and ethanol) were examined against liver fibrosis induced by carbon tetrachloride in rats. Results The evaluation was done through measuring antioxidant parameters; glutathione (GSH), total superoxide dismutase (SOD) and malondialdehyde (MDA). Liver marker enzymes; succinate and lactate dehydrogenases (SDH and LDH), glucose-6-phosphatase (G-6-Pase), acid phosphatase (AP), 5'- nucleotidase (5'NT) and liver function enzymes; aspartate and alanine aminotransferases (AST and ALT) as well as cholestatic markers; alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin were estimated. Liver histopathological analysis and collagen content were also evaluated. Treatments with the selected extracts significantly increased GSH, SOD, SDH, LDH, G-6-Pase, AP and 5'NT. However, MDA, AST, ALT ALP, GGT and total bilirubin were significantly decreased. Conclusions Extracts of ginger, particularly the ethanol one resulted in an attractive candidate for the treatment of liver fibrosis induced by CCl4. Further studies are required in order to identify the molecules responsible of the pharmacological activity. PMID:21689445

  2. Pinworm infection masquerading as colorectal liver metastasis.

    Science.gov (United States)

    Roberts, K J; Hubscher, S; Mangat, K; Sutcliffe, R; Marudanayagam, R

    2012-09-01

    Enterobius vermicularis is responsible for a variety of diseases but rarely affects the liver. Accurate characterisation of suspected liver metastases is essential to avoid unnecessary surgery. In the presented case, following a diagnosis of rectal cancer, a solitary liver nodule was diagnosed as a liver metastasis due to typical radiological features and subsequently resected. At pathological assessment, however, a necrotic nodule containing E. vermicularis was identified. Solitary necrotic nodules of the liver are usually benign but misdiagnosed frequently as malignant due to radiological features. It is standard practice to diagnose colorectal liver metastases solely on radiological evidence. Without obtaining tissue prior to liver resection, misdiagnosis of solitary necrotic nodules of the liver will continue to occur.

  3. RELATION BETWEEN PREECLAMPSIA AND CARDIAC ENZYMES

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    Rubina Aziz

    2010-12-01

    Full Text Available Abstract    INTRODUCTION: Preeclampsia affects about 5-10% of all pregnancies and is a major cause of maternal, fetal and neonatal mortality and morbidity. The cardiovascular system undergoes a host of changes in association with development of preeclampsia. LDH is a useful biochemical marker that reflects the severity of the occurrence of preeclampsia.    METHOD AND MATERIALS: One hundred pregnant women were selected for this study, 50 normal pregnant women as controls and 50 preeclamptic women as the study group.  Cardiac enzymes (serum LDH, serum AST, serum CK and serum CKMB of these women were analyzed.    RESULTS: Mean Serum LDH and mean serum AST concentrations were significantly higher in preeclamptic patients compared to normal pregnant women (348.34 ± 59.17 vs. 255.92 ± 43.26, P < 0.01 and (34.32 ± 10.37 vs. 22.06 ± 5.10, P < 0.01 respectively.     CONCLUSION: LDH and AST may be increased due to liver damage. This endothelial vascular damage is the main cause in the occurrence of preeclampsia. Higher levels of LDH and AST are very useful markers to identify the occurrence of preeclampsia.      Keywords: LDH, Preeclampsia, AST, Cardiac Enzymes.

  4. Liver enzyme elevations in a cohort of HIV/AIDS patients on first-line ...

    African Journals Online (AJOL)

    Introduction: All antiretroviral therapies (ARTs) are potentially toxic to the liver. In sub-Saharan Africa, the rising incidence of ART induced adverse events has complicated treatment leading to recent revisions of Namibian ART guidelines. Unfortunately there have been limited studies to date evaluating ART induced liver ...

  5. Indicators of inflammation and cellular damage in chronic asymptomatic or oligosymptomatic alcoholics: correlation with alteration of bilirubin and hepatic and pancreatic enzymes

    Directory of Open Access Journals (Sweden)

    Borini Paulo

    1999-01-01

    Full Text Available Biochemical and hematimetric indicators of inflammation and cell damage were correlated with bilirubin and hepatic and pancreatic enzymes in 30 chronic male alcoholics admitted into psychiatric hospital for detoxification and treatment of alcoholism. Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, and total bilirubin were altered, respectively, in 90%, 63%, 87%, 23% and 23% of the cases. None of the indicators of inflammation (lactic dehydrogenase, altered in 16% of the cases; alpha-1 globulin, 24%; alpha-2 globulin, 88%; leucocyte counts, 28% was correlated with alterations of bilirubin or liver enzymes. Lactic dehydrogenase was poorly sensitive for detection of hepatocytic or muscular damage. Alterations of alpha-globulins seemed to have been due more to alcohol metabolism-induced increase of lipoproteins than to inflammation. Among indicators of cell damage, serum iron, increased in 40% of the cases, seemed to be related to liver damage while creatine phosphokinase, increased in 84% of the cases, related to muscle damage. Hyperamylasemia was found in 20% of the cases and significantly correlated with levels of bilirubin, alkaline phosphatase and gamma-glutamyltransferase. It was indicated that injuries of liver, pancreas, salivary glands, and muscle occurred in asymptomatic or oligosymptomatic chronic alcoholics.

  6. Hepatoprotective effect of methanolic Tanacetum parthenium extract on CCl4-induced liver damage in rats

    Directory of Open Access Journals (Sweden)

    Yavar Mahmoodzadeh

    Full Text Available The purpose of this study was to investigate the effects of Tanacetum Parthenium Extract (TPE on Lipid peroxidation, antioxidant enzymes, biochemical factors, and liver enzymes in the rats damaged by Carbon Tetrachloride (CCl4.54 male Wistar rats were divided into 9 groups each consisting of 6 rats. Two of the groups were control groups (normal and damage control groups, 4 of them were exposure groups which were respectively administered with 40, 80, and 120 mg/kg of TPE and silymarin for 14 days before being damaged by CCl4, and the other 3 groups were post-treatment groups which received 80 and 120 mg/kg of TPE and silymarin 2, 6, 24, and 48 h after being injected with CCl4. At the end of the study, biochemical factors, serum liver enzymes, malondialdehyde level, antioxidant enzymes, and liver morphology were assayed.Pre- and post-treatment with TPE could significantly decrease ALT, AST, ALP, TG, LDL, TC, and glucose levels and increase HDL, and albumin levels and catalase, SOD, and GPx activities compared to the CCl4-damaged control group.The results of this study are indicative of the antioxidant activity of TPE, its potential hepatoprotective effects, and its probable therapeutic properties for laboratory animals damaged by CCl4. Keywords: Tanacetum parthenium, Carbon tetrachloride, Oxidative stress, Antioxidant enzymes, Liver damage

  7. Coenzyme metabolism in rat liver transketolase

    International Nuclear Information System (INIS)

    Gorbach, Z.V.; Kubyshin, V.L.; Maglysh, S.S.; Zabrodskaya, S.V.

    1987-01-01

    On the basis of the results of kinetic investigations, two binding sites for hydroxythiamine diphosphate were determined in apotransketolase, with sharply differing values of K/sub i/: (7-22) x 10 -9 and (13.0-19.7) x 10 -8 M. A study was made of the turnover rate of thiamine diphosphate in holotransketolase in rat liver tissue by a radioisotope method, using [ 14 C] thiamine as the labeled precursor. The half-substitution time and rate constant of degradation of the coenzyme in transketolase are close in absolute values to the analogous indices for the protein portion of the enzyme and constitute 153 h and 0.108 day -1 , respectively. Rat liver transketolase exists in vivo in the form of a substituted α-carbanion. Replacement of thiamine diphosphate by hydroxythiamine diphosphate in the holoenzyme has no effect on the formation of the intermediate α-carbanion form of the enzyme

  8. Carvacrol attenuates N-nitrosodiethylamine induced liver injury in experimental Wistar rats

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    Balan Rajan

    2015-06-01

    Full Text Available Carvacrol is a main constituent in the essential oils of countless aromatic plants including Origanum Vulgare and Thymus vulgari, which has been assessed for substantial pharmacological properties. In recent years, notable research has been embarked on to establish the biological actions of Carvacrol for its promising use in clinical applications. The present study is an attempt to reveal the protective role of Carvacrol against N-Nitrosodiethylamine (DEN induced hepatic injury in male Wistar albino rats. DEN is an egregious toxin, present in numerous environmental factors, which enhances chemical driven liver damage by inducing oxidative stress and cellular injury. Administration of DEN (200 mg/kg bodyweight, I.P to rats results in elevated marker enzymes (in both serum and tissue. Carvacrol (15 mg/kg body weight suppressed the elevation of marker enzymes (in both serum and tissue and augmented the antioxidants levels. The hoisted activities of Phase I enzymes and inferior activities of Phase II enzymes were observed in DEN-administered animals, whereas Carvacrol treated animals showed improved near normal activity. Histological observations also support the protective role of Carvacrol against DEN induced liver damage. Final outcome from our findings intimate that Carvacrol might be beneficial in attenuating toxin induced liver damage.

  9. Acute renal failure, thrombocytopenia, and elevated liver enzymes after concurrent abuse of alcohol and cocaine

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    Alireza Hosseinnezhad

    2011-05-01

    Full Text Available Cocaine has been associated with known adverse effects on cardiac, cerebrovascular and pulmonary systems. However, the effect of cocaine on other organs has not been extensively reported. A middle age man presented with abdominal pain and nausea after inhalation of crack cocaine. On admission, he was found to be hypertensive and tachycardic. Physical examination revealed mild abdominal tenderness without rebound. Laboratory investigations were significant for acute kidney failure with elevated serum creatinine (3.72 mg/dL, thrombocytopenia (platelet count 74,000/UL, elevated alanine and aspartate transaminases (ALT 331 U/L; AST 462 U/L and elevated creatine phosphokinase (CPK 5885 U/L. Urine toxicology screening solely revealed cocaine. A clinical diagnosis of cocaine toxicity was made and patient was admitted to the intensive care unit because of multi organ failure. Despite downward trending of liver enzymes during the hospital course, he continued to have residual renal insufficiency and a low platelet count at the time of discharge. In a patient with history of recent cocaine use presenting with these manifestations, cocaine itself should be considered as a likely cause.

  10. Enzyme clusters during the metamorphic period of Ambystoma mexicanum: role of thyroid hormone

    NARCIS (Netherlands)

    Lamers, W. H.; Mooren, P. G.; de Graaf, A.

    1982-01-01

    Enzyme activities and DNA content have been measure in axolotl liver during the metamorphic period (4-8 months after spawning). Three different types of enzyme activity profiles were observed. In the type I profile (carbamoyl-phosphate synthase, arginase, ornithine transcarbamoylase, and glutamate

  11. Imidacloprid enhances liver damage in Wistar rats: Biochemical, oxidative damage and histological assessment

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    Sana Chakroun

    2017-12-01

    Full Text Available Objective: To investigate the potential adverse effects of imidacloprid on biochemical parameters, oxidative stress and liver damage induced in the rat by oral sub-chronic imidaclopride exposure. Methods: Rats received three different doses of imidacloprid (1/45, 1/22 and 1/10 of LD50 given through gavage for 60 days. Two dozen of male Wistar rats were randomly divided into four experimental groups. Liver damage was determined by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase leakages. The prooxidant-antioxydant status in hepatic tissue homogenate was evaluated by measuring the degree of lipid peroxidation, the antioxidant enzymes activities such as catalase, superoxide dismutase and glutathione peroxidase (GPx. Results: The relative liver weight was significantly higher than that of control and other treated groups at the highest dose 1/10 of LD50 of imidacloprid. Additionally, treatment of rats with imidacloprid significantly increased liver lipid peroxidation (P ≤ 0.05 or 0.01 which went together with a significant decrease in the levels of superoxide dismutase and catalase activities. Parallel to these changes, imidacloprid treatment enhanced liver damage as evidence by sharp increase in the liver enzyme activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase. These results were also confirmed by histopathology. Conclusions: In light of the available data, it is our thought that after imidacloprid sub-chronic exposure, depletion of antioxidant enzymes is accompanied by induction of potential oxidative stress in the hepatic tissues that might affect the function of the liver which caused biochemical and histopathological alteration.

  12. Subcellular localization of pituitary enzymes

    Science.gov (United States)

    Smith, R. E.

    1970-01-01

    A cytochemical procedure is reported for identifying subcellular sites of enzymes hydrolyzing beta-naphthylamine substrates, and to study the sites of reaction product localization in cells of various tissues. Investigations using the substrate Leu 4-methoxy-8-naphthylamine, a capture with hexonium pararosaniline, and the final chelation of osmium have identified the hydrolyzing enzyme of rat liver cells; this enzyme localized on cell membranes with intense deposition in the areas of the parcanaliculi. The study of cells in the anterior pituitary of the rat showed the deposition of reaction product on cell membrane; and on the membranes of secretion granules contained within the cell. The deposition of reaction product on the cell membrane however showed no increase or decrease with changes in the physiological state of the gland and release of secretion granules from specific cells.

  13. Pyruvate dehydrogenase complex and lactate dehydrogenase as targets for therapy of acute liver failure.

    Science.gov (United States)

    Ferriero, Rosa; Nusco, Edoardo; De Cegli, Rossella; Carissimo, Annamaria; Manco, Giuseppe; Brunetti-Pierri, Nicola

    2018-03-23

    Acute liver failure is a rapidly progressive deterioration of hepatic function resulting in high mortality and morbidity. Metabolic enzymes can translocate in the nucleus to regulate histone acetylation and gene expression. Levels and activities of pyruvate dehydrogenase complex (PDHC) and lactate dehydrogenase (LDH) were evaluated in nuclear fractions of livers of mice exposed to various hepatotoxins including CD95-Ab, α-amanitin, and acetaminophen. Whole-genome gene expression profiling by RNA-seq was performed in livers of mice with acute liver failure and analyzed by Gene Ontology Enrichment Analysis. Efficacy of histone acetyltransferase inhibitor garcinol and LDH inhibitor galloflavin at reducing liver damage was evaluated in mice with induced hepatotoxicity. Levels and activities of PDHC and LDH were increased in cytoplasmatic and nuclear fractions of livers of mice with acute liver failure. The increase of nuclear PDHC and LDH was associated with increased concentrations of acetyl-coA and lactate in nuclear fractions, and histone H3 hyper-acetylation. Gene expression in livers of mice with acute liver failure suggested that increased histone H3 acetylation induces the expression of genes related to response to damage. Reduced histone acetylation by the histone acetyltransferase inhibitor garcinol decreased liver damage and improved survival in mice with acute liver failure. Knock-down of PDHC or LDH improved viability in cells exposed to a pro-apoptotic stimulus. Treatment with the LDH inhibitor galloflavin that was also found to inhibit PDHC, reduced hepatic necrosis, apoptosis, and expression of pro-inflammatory cytokines in mice with acute liver failure. Mice treated with galloflavin also showed a dose-response increase in survival. PDHC and LDH translocate to the nucleus and are targets for therapy of acute liver failure. Acute liver failure is a rapidly progressive and life-threatening deterioration of liver function resulting in high mortality and

  14. Early plasmapheresis and rituximab for acute humoral rejection after ABO-compatible liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Nassim Kamar; Laurence Lavayssière; Fabrice Muscari; Janick Selves; Céline Guilbeau-Frugier; Isabelle Cardeau; Laure Esposito; Olivier Cointault; Marie Béatrice Nogier; Jean Marie Peron; Philippe Otal; Marylise Fort; Lionel Rostaing

    2009-01-01

    Acute humoral rejection (AHR) is uncommon after ABOcompatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Liver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab.Liver enzymes returned to within normal range 18 dafter diagnosis. Liver biopsies, at 3 and 9 mo post-transplant,showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.

  15. Fisetin Modulates Antioxidant Enzymes and Inflammatory Factors to Inhibit Aflatoxin-B1 Induced Hepatocellular Carcinoma in Rats

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    Brajesh Kumar Maurya

    2016-01-01

    Full Text Available Fisetin, a known antioxidant, has been found to be cytotoxic against certain cell lines. However, the mechanism by which it inhibits tumor growth in vivo remains unexplored. Recently, we have demonstrated that Aflatoxin-B1 (AFB1 induced hepatocarcinogenesis is associated with activation of oxidative stress-inflammatory pathway in rat liver. The present paper describes the effect of in vivo treatment with 20 mg/kg b.w. Fisetin on antioxidant enzymes vis-a-vis oxidative stress level and on the profile of certain proinflammatory cytokines in the hepatocellular carcinoma (HCC induced by two doses of 1 mg/kg b.w. AFB1 i.p. in rats. The reduced levels of most of the antioxidant enzymes, coinciding with the enhanced level of reactive oxygen species in the HCC liver, were observed to regain their normal profiles due to Fisetin treatment. Also, Fisetin treatment could normalize the enhanced expression of TNFα and IL1α, the two proinflammatory cytokines, reported to be involved in HCC pathogenesis. These observations were consistent with the regression of neoplastic lesion and declined GST-pi (placental type glutathione-S-transferase level, a HCC marker, in the liver of the Fisetin treated HCC rats. The findings suggest that Fisetin attenuates oxidative stress-inflammatory pathway of AFB1 induced hepatocarcinogenesis.

  16. Induction of biotransformation enzymes by the carcinogenic air-pollutant 3-nitrobenzanthrone in liver, kidney and lung, after intra-tracheal instillation in rats.

    Science.gov (United States)

    Mizerovská, Jana; Dračínská, Helena; Frei, Eva; Schmeiser, Heinz H; Arlt, Volker M; Stiborová, Marie

    2011-02-28

    3-Nitrobenzanthrone (3-NBA), a carcinogenic air pollutant, was investigated for its ability to induce cytochrome P450 (CYP) 1A1/2 and NAD(P)H:quinone oxidoreductase (NQO1) in liver, kidney and lung of rats treated by intra-tracheal instillation. The organs used were from a previous study performed to determine the persistence of 3-NBA-derived DNA adducts in target and non-target tissues (Bieler et al., Carcinogenesis 28 (2007) 1117-1121, [22]). NQO1 is the enzyme reducing 3-NBA to N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) and CYP1A enzymes oxidize a human metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), to yield the same reactive intermediate. 3-NBA and 3-ABA are both activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and from liver and kidney. Each compound generated the same five DNA adducts detectable by (32)P-postlabelling. When hepatic cytosols from rats treated with 0.2 or 2mg/kg body weight of 3-NBA were incubated with 3-NBA, DNA adduct formation was 3.2- and 8.6-fold higher, respectively, than in incubations with cytosols from control animals. Likewise, cytosols isolated from lungs and kidneys of rats exposed to 3-NBA more efficiently activated 3-NBA than those of control rats. This increase corresponded to an increase in protein levels and enzymatic activities of NQO1. Incubations of hepatic, pulmonary or renal microsomes of 3-NBA-treated rats with 3-ABA led to an 9.6-fold increase in DNA-adduct formation relative to controls. The highest induction in DNA-adduct levels was found in lung. The stimulation of DNA-adduct formation correlated with expression of CYP1A1/2 induced by the intra-tracheal instillation of 3-NBA. The results demonstrate that 3-NBA induces NQO1 and CYP1A1/2 in livers, lungs and kidneys of rats after intra-tracheal instillation, thereby enhancing its own genotoxic and carcinogenic potential. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. Rat liver contains a limited number of binding sites for hepatic lipase

    NARCIS (Netherlands)

    G.C. Schoonderwoerd (Kees); A.J.M. Verhoeven (Adrie); H. Jansen (Hans)

    1994-01-01

    textabstractThe binding of hepatic lipase to rat liver was studied in an ex vivo perfusion model. The livers were perfused with media containing partially purified rat hepatic lipase or bovine milk lipoprotein lipase. The activity of the enzymes was determined in the

  18. Inhibitory Effects of Dimethyllirioresinol, Epimagnolin A, Eudesmin, Fargesin, and Magnolin on Cytochrome P450 Enzyme Activities in Human Liver Microsomes

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    Ju-Hyun Kim

    2017-05-01

    Full Text Available Magnolin, epimagnolin A, dimethyllirioresinol, eudesmin, and fargesin are pharmacologically active tetrahydrofurofuranoid lignans found in Flos Magnoliae. The inhibitory potentials of dimethyllirioresinol, epimagnolin A, eudesmin, fargesin, and magnolin on eight major human cytochrome P450 (CYP enzyme activities in human liver microsomes were evaluated using liquid chromatography–tandem mass spectrometry to determine the inhibition mechanisms and inhibition potency. Fargesin inhibited CYP2C9-catalyzed diclofenac 4’-hydroxylation with a Ki value of 16.3 μM, and it exhibited mechanism-based inhibition of CYP2C19-catalyzed [S]-mephenytoin 4’-hydroxylation (Ki, 3.7 μM; kinact, 0.102 min−1, CYP2C8-catalyzed amodiaquine N-deethylation (Ki, 10.7 μM; kinact, 0.082 min−1, and CYP3A4-catalyzed midazolam 1’-hydroxylation (Ki, 23.0 μM; kinact, 0.050 min−1 in human liver microsomes. Fargesin negligibly inhibited CYP1A2-catalyzed phenacetin O-deethylation, CYP2A6-catalyzed coumarin 7-hydroxylation, CYP2B6-catalyzed bupropion hydroxylation, and CYP2D6-catalyzed bufuralol 1’-hydroxylation at 100 μM in human liver microsomes. Dimethyllirioresinol weakly inhibited CYP2C19 and CYP2C8 with IC50 values of 55.1 and 85.0 μM, respectively, without inhibition of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2D6, and CYP3A4 activities at 100 μM. Epimagnolin A, eudesmin, and magnolin showed no the reversible and time-dependent inhibition of eight major CYP activities at 100 μM in human liver microsomes. These in vitro results suggest that it is necessary to investigate the potentials of in vivo fargesin-drug interaction with CYP2C8, CYP2C9, CYP2C19, and CYP3A4 substrates.

  19. Simultaneous quantification of the abundance of several cytochrome P450 and uridine 5'-diphospho-glucuronosyltransferase enzymes in human liver microsomes using multiplexed targeted proteomics.

    Science.gov (United States)

    Achour, Brahim; Russell, Matthew R; Barber, Jill; Rostami-Hodjegan, Amin

    2014-04-01

    Cytochrome P450 (P450) and uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes mediate a major proportion of phase I and phase II metabolism of xenobiotics. In vitro-in vivo extrapolation (IVIVE) of hepatic clearance in conjunction with physiologically-based pharmacokinetics (PBPK) has become common practice in drug development. However, prediction of xenobiotic kinetics in virtual populations requires knowledge of both enzyme abundances and the extent to which these correlate. A multiplexed quantification concatemer (QconCAT) strategy was used in this study to quantify the expression of several P450 and UGT enzymes simultaneously and to establish correlations between various enzyme abundances in 24 individual liver samples (ages 27-66, 14 male). Abundances were comparable to previously reported values, including CYP2C9 (40.0 ± 26.0 pmol mg(-1)), CYP2D6 (11.9 ± 13.2 pmol mg(-1)), CYP3A4 (68.1 ± 52.3 pmol mg(-1)), UGT1A1 (33.6 ± 34.0 pmol mg(-1)), and UGT2B7 (82.9 ± 36.1 pmol mg(-1)), expressed as mean ± S.D. Previous reports of correlations in expression of various P450 (CYP3A4/CYP3A5*1/*3, CYP2C8/CYP2C9, and CYP3A4/CYP2B6) were confirmed. New correlations were demonstrated between UGTs [including UGT1A6/UGT1A9 (r(s) = 0.82, P enzymes were shown to be correlated [including CYP1A2/UGT2B4 (r(s) = 0.67, P = 0.0002)]. The expression of CYP3A5 in individuals with *1/*3 genotype (n = 11) was higher than those with *3/*3 genotype (n = 10) (P history of smoking or alcohol use on enzyme expression was observed; however, expression of several enzymes declined with age. The correlation matrix produced for the first time by this study can be used to generate more realistic virtual populations with respect to abundance of various enzymes.

  20. Hepatocyte Hypoxia Inducible Factor-1 Mediates the Development of Liver Fibrosis in a Mouse Model of Nonalcoholic Fatty Liver Disease.

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    Omar A Mesarwi

    Full Text Available Obstructive sleep apnea (OSA is associated with the progression of non-alcoholic fatty liver disease (NAFLD to steatohepatitis and fibrosis. This progression correlates with the severity of OSA-associated hypoxia. In mice with diet induced obesity, hepatic steatosis leads to liver tissue hypoxia, which worsens with exposure to intermittent hypoxia. Emerging data has implicated hepatocyte cell signaling as an important factor in hepatic fibrogenesis. We hypothesized that hepatocyte specific knockout of the oxygen sensing α subunit of hypoxia inducible factor-1 (HIF-1, a master regulator of the global response to hypoxia, may be protective against the development of liver fibrosis.Wild-type mice and mice with hepatocyte-specific HIF-1α knockout (Hif1a-/-hep were fed a high trans-fat diet for six months, as a model of NAFLD. Hepatic fibrosis was evaluated by Sirius red stain and hydroxyproline assay. Liver enzymes, fasting insulin, and hepatic triglyceride content were also assessed. Hepatocytes were isolated from Hif1a-/-hep mice and wild-type controls and were exposed to sustained hypoxia (1% O2 or normoxia (16% O2 for 24 hours. The culture media was used to reconstitute type I collagen and the resulting matrices were examined for collagen cross-linking.Wild-type mice on a high trans-fat diet had 80% more hepatic collagen than Hif1a-/-hep mice (2.21 μg collagen/mg liver tissue, versus 1.23 μg collagen/mg liver tissue, p = 0.03, which was confirmed by Sirius red staining. Body weight, liver weight, mean hepatic triglyceride content, and fasting insulin were similar between groups. Culture media from wild-type mouse hepatocytes exposed to hypoxia allowed for avid collagen cross-linking, but very little cross-linking was seen when hepatocytes were exposed to normoxia, or when hepatocytes from Hif1a-/-hep mice were used in hypoxia or normoxia.Hepatocyte HIF-1 mediates an increase in liver fibrosis in a mouse model of NAFLD, perhaps due to liver

  1. Aspects of the regulation of long-chain fatty acid oxidation in bovine liver

    International Nuclear Information System (INIS)

    Jesse, B.W.; Emery, R.S.; Thomas, J.W.

    1986-01-01

    Factors involved in regulation of bovine hepatic fatty acid oxidation were examined using liver slices. Fatty acid oxidation was measured as the conversion of l-[ 14 C] palmitate to 14 CO 2 and total [ 14 C] acid-soluble metabolites. Extended (5 to 7 d) fasting of Holstein cows had relatively little effect on palmitate oxidation to acid-soluble metabolites by liver slices, although oxidation to CO 2 was decreased. Feeding a restricted roughage, high concentrate ration to lactating cows resulted in inhibition of palmitate oxidation. Insulin, glucose, and acetate inhibited palmitate oxidation by bovine liver slices. The authors suggest the regulation of bovine hepatic fatty acid oxidation may be less dependent on hormonally induced alterations in enzyme activity as observed in rat liver and more dependent upon action of rumen fermentation products or their metabolites on enzyme systems involved in fatty acid oxidation

  2. [Liver transplantation for the treatment of hyperammonemia due to urea cycle disorder: report of four cases].

    Science.gov (United States)

    Zhu, Zhijun; Sun, Liying; Wei, Lin; Qu, Wei; Zeng, Zhigui; Liu, Ying; Zhang, Liang; He, Enhui; Wang, Dong

    2015-02-01

    To analyze clinical efficacy and prognosis of liver transplantation in children with hyperammonemia caused by urea cycle disorders. A retrospective analysis was performed on the occurrence of disease, operation and the follow-up post liver transplantation in 4 patients with urea cycle disorders who underwent liver transplantation during June 2001 to May 2014. Four girls were diagnosed with ornithine carbamoyl transferase deficiency by genetic test. They had the clinical onset at the age of 1.5 to 3.0 years. Liver transplantation had been performed at their age of 53.9 months, 40.6 months, 40.3 months and 22.8 months, respectively. The grafts of case 1 and case 2 were from left lateral lobe of liver of cadaveric donor, the graft of case 3 was from left lateral lobe of liver of a living donor, the graft of case 4 was a whole liver of a dead child. The liver function of 4 patients gradually returned to normal, blood ammonia levels were normal and restored the normal diet, 4 children were discharged on postoperative 25-30 days. Regular follow-up was done, the liver function, biochemical features and growth status have been followed up for 162.2 months, 124.2 months, 12.0 months and 4.8 months after liver transplantation, respectively. Now, all the four cases are healthy and growth is normal. Liver transplantation is an important way to the patients with severe hyperammonemia caused by urea cycle disorders. In this study, the patients with ornithine carbamoyl transferase defect got satisfactory long-term outcome after liver transplantation.

  3. Panhypopituitarism due to Absence of the Pituitary Stalk: A Rare Aetiology of Liver Cirrhosis.

    Science.gov (United States)

    Gonzalez Rozas, Marta; Hernanz Roman, Lidia; Gonzalez, Diego Gonzalez; Pérez-Castrillón, José Luis

    2016-01-01

    Studies have established a relationship between hypothalamic-pituitary dysfunction and the onset of liver damage, which may occasionally progress to cirrhosis. Patients with hypopituitarism can develop a metabolic syndrome-like phenotype. Insulin resistance is the main pathophysiological axis of metabolic syndrome and is the causal factor in the development of nonalcoholic fatty liver disease (NAFLD). We present the case of a young patient with liver cirrhosis of unknown aetiology that was finally attributed to panhypopituitarism.

  4. Effects of sub-lethal dose of γ-irradiation on lysosomal enzymes in tissue of pigeon

    International Nuclear Information System (INIS)

    Shah, V.C.; Gadhia, P.K.

    1979-01-01

    Effects of total body γ-irradiation with sub-lethal dose (300 rad) on three lysosomal enzymes namely acid phosphatase, ribonuclease-II and deoxyribonuclease-II have been studied in pigeons. Liver, kidney and spleen were the tissues studied at different intervals like 1-h, 24-h, 48-h, and 72-h of irradiation. The specific activities ('crude' fraction) of acid phosphatase and ribonuclease-II increased significantly in spleen and liver at 48-h of irradiation. The activity of deoxyribonuclease-II in liver and spleen was increased only at 72-h post-irradiation. On the other hand, the total activities of three lysosomal enzymes did not show remarkable change throughout 72-h of irradiation. (author)

  5. Protective effect of bicyclol on tetracycline-induced fatty liver in mice

    International Nuclear Information System (INIS)

    Yu, Hong-Yan; Wang, Bao-Lian; Zhao, Jing; Yao, Xiao-Min; Gu, Yu; Li, Yan

    2009-01-01

    Peroxisome proliferators-activated receptor α (PPARα) and oxidative stress are two important pathological factors in non-alcoholic fatty liver disease (NAFLD). Tetracycline-induced fatty liver was partly due to the disturbance of mitochondrial fatty acids β-oxidation regulated by PPARα. Bicyclol was found to protect against high fat diet-induced fatty liver through modulating PPARα and clearing reactive oxygen species (ROS). The present study was performed to further investigate the effect of bicyclol on tetracycline-induced fatty liver and related mechanism in mice. Bicyclol (75, 150, 300 mg/kg) was given orally three times in two consecutive days. Tetracycline (200 mg/kg) was injected intraperitoneally 1 h after the last administration of bicyclol. Oxidative stress, mitochondrial function, PPARα and its target genes were evaluated by biochemical and RT-PCR analysis. The activity of CYP4A was assessed by liquid chromatography/mass spectrometry (LC/MS) method. Bicyclol significantly protected against tetracycline-induced fatty liver by reducing the accumulation of hepatic lipids and elevation of serum aminotransferase. In addition, bicyclol remarkably alleviated the over-production of thiobarbituric acid-reactive substance. The reduced activity of mitochondrial respiratory chain (MRC) complexes I and IV and mitochondrial permeability transition (MPT) were also improved by bicyclol. Furthermore, bicyclol inhibited the decrease of PPARα expression and its target genes, including long-chain acyl CoA dehydrogenase (LCAD), acetyl CoA oxidase (AOX) and CYP4A at mRNA and enzyme activity level. Bicyclol protected against tetracycline-induced fatty liver mainly through modulating the disturbance of PPARα pathway and ameliorating mitochondrial function.

  6. Effects of the hepatocarcinogen nafenopin, a peroxisome proliferator, on the activities of rat liver glutathione-requiring enzymes and catalase in comparison to the action of phenobarbital.

    Science.gov (United States)

    Furukawa, K; Numoto, S; Furuya, K; Furukawa, N T; Williams, G M

    1985-10-01

    The biochemical effects in the livers of male rats of prolonged administration of the experimental hepatocarcinogen nafenopin, a hypolipidemic agent and peroxisome proliferator, were compared to those of another experimental liver carcinogen, phenobarbital, which acts as a neoplasm promoter. Feeding of nafenopin, 0.03 mmol/kg basal diet for up to 24 weeks increased the numbers of hepatic peroxisomes, increased catalase activity, markedly decreased cytosolic glutathione transferase activities toward two substrates, decreased cytosolic glutathione peroxidase activities toward H2O2 and two organic peroxides, and suppressed the age-related increase in gamma-glutamyl transpeptidase activity. In contrast the livers of rats fed an equimolar concentration of phenobarbital displayed increases in cytosolic glutathione transferase activities and enhancement of gamma-glutamyl transpeptidase activity but no changes in glutathione peroxidase activities. There was also an enhancement of catalase activity without apparent increase in peroxisome number. Enzyme kinetic analyses revealed that the cytosolic glutathione transferase activities toward two halogenonitrobenzene substrates were inhibited in the rats fed nafenopin and displayed elevated Km and decreased Vmax. Kinetic studies of glutathione transferase activities in which nafenopin was mixed with normal rat liver cytosols in the assay system revealed competitive type inhibition toward 1-chloro-2,4-dinitrobenzene and a noncompetitive type of inhibition toward 3,4-dichloronitrobenzene. Likewise activities of glutathione peroxidases toward H2O2 and cumene hydroperoxide were suppressed by in vitro addition. Thus the effects of nafenopin and phenobarbital on liver biochemistry were very different. The inhibition of hepatic biotransformation and scavenger systems by nafenopin is suggested to be relevant to its hepatocarcinogenicity.

  7. Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

    International Nuclear Information System (INIS)

    Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki

    2013-01-01

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA

  8. Diphenylarsinic acid, a chemical warfare-related neurotoxicant, promotes liver carcinogenesis via activation of aryl hydrocarbon receptor signaling and consequent induction of oxidative DAN damage in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Min; Yamada, Takanori; Yamano, Shotaro; Kato, Minoru; Kakehashi, Anna; Fujioka, Masaki; Tago, Yoshiyuki; Kitano, Mistuaki; Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp

    2013-11-15

    Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. Inorganic arsenic is carcinogenic in humans and its organic arsenic metabolites are carcinogenic in animal studies, raising serious concerns about the carcinogenicity of DPAA. However, the carcinogenic potential of DPAA has not yet been evaluated. In the present study we found that DPAA significantly enhanced the development of diethylnitrosamine-induced preneoplastic lesions in the liver in a medium-term rat liver carcinogenesis assay. Evaluation of the expression of cytochrome P450 (CYP) enzymes in the liver revealed that DPAA induced the expression of CYP1B1, but not any other CYP1, CYP2, or CYP3 enzymes, suggesting that CYP1B1 might be the enzyme responsible for the metabolic activation of DPAA. We also found increased oxidative DNA damage, possibly due to elevated CYP1B1 expression. Induction of CYP1B1 has generally been linked with the activation of AhR, and we found that DPAA activates the aryl hydrocarbon receptor (AhR). Importantly, the promotion effect of DPAA was observed only at a dose that activated the AhR, suggesting that activation of AhR and consequent induction of AhR target genes and oxidative DNA damage plays a vital role in the promotion effects of DPAA. The present study provides, for the first time, evidence regarding the carcinogenicity of DPAA and indicates the necessity of comprehensive evaluation of its carcinogenic potential using long-term carcinogenicity studies. - Highlights: • DPAA, an environmental neurotoxicant, promotes liver carcinogenesis in rats. • DPAA is an activator of AhR signaling pathway. • DPAA promoted oxidative DNA damage in rat livers. • AhR target gene CYP 1B1 might be involved in the metabolism of DPAA.

  9. Hepatocurative potential of sesquiterpene lactones of Taraxacum officinale on carbon tetrachloride induced liver toxicity in mice.

    Science.gov (United States)

    Mahesh, A; Jeyachandran, R; Cindrella, L; Thangadurai, D; Veerapur, V P; Muralidhara Rao, D

    2010-06-01

    The hepatocurative potential of ethanolic extract (ETO) and sesquiterpene lactones enriched fraction (SL) of Taraxacum officinale roots was evaluated against carbon tetrachloride (CCl 4 ) induced hepatotoxicity in mice. The diagnostic markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin contents were significantly elevated, whereas significant reduction in the level of reduced glutathione (GSH) and enhanced hepatic lipid peroxidation, liver weight and liver protein were observed in CCl 4 induced hepatotoxicity in mice. Post-treatment with ETO and SL significantly protected the hepatotoxicity as evident from the lower levels of hepatic enzyme markers, such as serum transaminase (ALT, AST), ALP and total bilirubin. Further, significant reduction in the liver weight and liver protein in drug-treated hepatotoxic mice and also reduced oxidative stress by increasing reduced glutathione content and decreasing lipid peroxidation level has been noticed. The histopathological evaluation of the liver also revealed that ETO and SL reduced the incidence of liver lesions induced by CCl 4 . The results indicate that sesquiterpene lactones have a protective effect against acute hepatotoxicity induced by the administration of CCl 4 in mice. Furthermore, observed activity of SL may be due to the synergistic action of two sesquiterpene lactones identified from enriched ethyl acetate fraction by HPLC method.

  10. Radiological evaluation of a liver simulator in comparison to a human real liver

    International Nuclear Information System (INIS)

    Toledo, Janine M.; Campos, Tarcisio P.R. de

    2009-01-01

    The present study evaluates the radiological features of a human real healthy liver reproducing its characteristics on a developed liver simulator. The radiological evaluation will be performed through radiological methods such as CT and X-ray images, density and weight measurements, as well as representation of the coloration and texture. According to literature, the liver is the highest weight organ and gland of the body, weighing approximately 1,5 kg. On the liver, the nutrients are absorbed from the digestive tract and are prosecuted and stored for future use by other organs. Also the liver is responsible for the neutralization and elimination of various toxic substances. Thus, it is an interface between the digestive system and the blood. Besides, this organ is the principal source of plasmatic proteins like the albumin, transport of graxos oily acids. Due to its proprieties, the liver holds a large amount of radionuclides on any uptake from external source. The liver simulator was designed to have the same density, weight and corresponding shape. The radiographic image was produced by conventional X-rays machine, in which the radiographic applied parameters were the same applied to abdomen. The result of the radiographic and CT images demonstrates radiological equivalence between the simulator and human real liver. Hounsfield number of the synthetic liver tissue was found on the range of human livers. Therefore, due to its similar shape, chemical composition, radiological response, the liver simulator can be used to investigate ionizing radiation procedures during radiation therapy intervention. (author)

  11. Panhypopituitarism due to Absence of the Pituitary Stalk: A Rare Aetiology of Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Marta Gonzalez Rozas

    2016-01-01

    Full Text Available Studies have established a relationship between hypothalamic-pituitary dysfunction and the onset of liver damage, which may occasionally progress to cirrhosis. Patients with hypopituitarism can develop a metabolic syndrome-like phenotype. Insulin resistance is the main pathophysiological axis of metabolic syndrome and is the causal factor in the development of nonalcoholic fatty liver disease (NAFLD. We present the case of a young patient with liver cirrhosis of unknown aetiology that was finally attributed to panhypopituitarism.

  12. Changes of plasma VEGF levels and liver function in patients with liver cancer before and after interventional treatment

    International Nuclear Information System (INIS)

    Li Jia; Qi Jun; Gao Jia

    2011-01-01

    To explore the effect of the interventional treatment for the angiogenesis and liver function in patients with liver cancer within short time, enzyme linked immunosorbent assay was used to determine the level of VEGF in plasma. The level of liver function was measured through automatic biochemistry analyzer. The results indicated that the level of VEGF in patients with liver cancer decreased after interventional treatment than that of before treatment (P<0.05). The level of total protein, albumin, alkaline phosphatase and total bile acid decreased after interventional treatment (P<0.05). The level of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin and indirect bilirubin were increased than before (P<0.05). The interventional treatment inhibit the expression of the VEGF in the tumor tissue and limited the angiogenesis within short time, but to some extent may caused the injury of the hepatocytes and the synthetic and excremental function in patients with liver cancer. (authors)

  13. Influence of matrix nature on the functional efficacy of biomedical cell product for the regeneration of damaged liver (experimental model of acute liver failure

    Directory of Open Access Journals (Sweden)

    S. V. Gautier

    2017-01-01

    Full Text Available Aim. A comparative analysis of the functional efficacy of biomedical cell products (BMCP for the regeneration of damaged liver based on biopolymer scaffolded porous and hydrogel matrices was performed on the experimental model of acute liver failure. Materials and methods. Matrices allowed for clinical use were employed for BMCP in the form of a sponge made from biopolymer nanostructured composite material (BNCM based on a highly purified bacterial copolymers of poly (β-hydroxybutyrate-co-β-oxyvalerate and polyethylene glycol and a hydrogel matrix from biopolymer microheterogeneous collagen-containing hydrogel (BMCH. Cellular component of BMCP was represented by liver cells and multipotent mesenchymal bone marrow stem cells. The functional efficacy of BMCP for the regeneration of damaged liver was evaluated on the experimental model of acute liver failure in Wistar rats (n = 40 via biochemical, morphological, and immunohistochemical methods. Results. When BMCP was implanted to regenerate the damaged liver on the basis of the scaffolded BNCM or hydrogel BMCH matrices, the lethality in rats with acute liver failure was absent; while in control it was 66.6%. Restoration of the activity of cytolytic enzyme levels and protein-synthetic liver function began on day 9 after modeling acute liver failure, in contrast to the control group, where recovery occurred only by days 18–21. Both matrices maintained the viability and functional activity of liver cells up to 90 days with the formation of blood vessels in BMCP. The obtained data confirm that scaffolded BNCM matrix and hydrogel BMCH matrix retain for a long time (up to 90 days the vital activity of the adherent cells in the BMCP composition, which allows using them to correct acute liver failure. At the same time, hydrogel matrix due to the presence of bioactive components contributes to the creation of the best conditions for adhesion and cell activity which accelerate the regeneration processes

  14. Ruptured subcapsular hematoma of the liver due to pre‑eclampsia ...

    African Journals Online (AJOL)

    Ruptured subcapsular hematoma of the liver (RSHL) can mimic ruptured interstitial pregnancy because each of these conditions occasionally presents at the same gestational period and both do manifest hemodynamic instability. The similarities between the two conditions pose a diagnostic challenge, especially in an ...

  15. Serum aminotransferases in nonalcoholic fatty liver disease are a signature of liver metabolic perturbations at the amino acid and Krebs cycle level.

    Science.gov (United States)

    Sookoian, Silvia; Castaño, Gustavo O; Scian, Romina; Fernández Gianotti, Tomas; Dopazo, Hernán; Rohr, Cristian; Gaj, Graciela; San Martino, Julio; Sevic, Ina; Flichman, Diego; Pirola, Carlos J

    2016-02-01

    Extensive epidemiologic studies have shown that cardiovascular disease and the metabolic syndrome (MetS) are associated with serum concentrations of liver enzymes; however, fundamental characteristics of this relation are currently unknown. We aimed to explore the role of liver aminotransferases in nonalcoholic fatty liver disease (NAFLD) and MetS. Liver gene- and protein-expression changes of aminotransferases, including their corresponding isoforms, were evaluated in a case-control study of patients with NAFLD (n = 42), which was proven through a biopsy (control subjects: n = 10). We also carried out a serum targeted metabolite profiling to the glycolysis, gluconeogenesis, and Krebs cycle (n = 48) and an exploration by the next-generation sequencing of aminotransferase genes (n = 96). An in vitro study to provide a biological explanation of changes in the transcriptional level and enzymatic activity of aminotransferases was included. Fatty liver was associated with a deregulated liver expression of aminotransferases, which was unrelated to the disease severity. Metabolite profiling showed that serum aminotransferase concentrations are a signature of liver metabolic perturbations, particularly at the amino acid metabolism and Krebs cycle level. A significant and positive association between systolic hypertension and liver expression levels of glutamic-oxaloacetic transaminase 2 (GOT2) messenger RNA (Spearman R = 0.42, P = 0.03) was observed. The rs6993 located in the 3' untranslated region of the GOT2 locus was significantly associated with features of the MetS, including arterial hypertension [P = 0.028; OR: 2.285 (95% CI: 1.024, 5.09); adjusted by NAFLD severity] and plasma lipid concentrations. In the context of an abnormal hepatic triglyceride accumulation, circulating aminotransferases rise as a consequence of the need for increased reactions of transamination to cope with the liver metabolic derangement that is associated with greater gluconeogenesis and

  16. ENZYMOCHEMICAL AND BIOCHEMICAL CHANGES IN THE LIVER OF RATS INDUCED BY FURFURAL

    Directory of Open Access Journals (Sweden)

    Dragana Veličković

    2011-06-01

    Full Text Available In today's industrial expansion of the chemical products, the liver is becoming increasingly important. Furfural (C4C3OCHO is a colorless liquid with pleasant aroma and it is partially soluble in water (8, 3% of weight. The elimination of furfural is done slowly through the kidneys and lungs, while the liver oxidizes it into pyromucic acid (C4C3OCOOH. Glucose-6-phosphate dehydrogenase (G6PD is a multi-component system of gluconeogenesis. Biochemical parameters (AST, ALT, glucose, γ-GT and alkaline phosphatase are important markers of liver damage.The aim of our study was to analyze the function of hepatocytes using biochemical parameters and to show the dynamics and topography in the development of changes in enzyme activity.The experiment was conducted on Wistar rats aged 6 weeks. The animals were divided into three groups. The control group received pure drinking water, the second group received a 50 mg/kg body weight (BW dose of furfural for seven days and in the third group the dose was progressively increased after which the animals were sacrificed. Biochemical methods were used to determine the parameters of liver damage. Enzyme-histochemical tests were performed on 8nm WKF 1150 cryostat cross sections which were stained according to Pearse (1968. The results are presented tables and graphs.The amount of enzymes and biochemical parameters in the control group were normal. In the group treated for 7 days, the activity of the enzymes was diffusely decreased while the biochemical parameters were increased. In the group of rats treated for 90 days, the periportal G6PD was constantly preserved. Biochemical parameters were different. The differences in all parameters were statistically significant (p<0.05 both in the group treated for 7 days and the group treated for 90 days. The same goes for the control group and the group treated for 7 days.Acute treatment with furfural causes damage to liver functions. The synthetic liver function is

  17. Liver toxicity related to herbs and dietary supplements: Online table of case reports. Part 2 of 5 series.

    Science.gov (United States)

    Brown, Amy Christine

    2017-09-01

    No online current list of potentially life-threatening, hepatotoxic herbs and dietary supplements based on PubMed case reports exists in a summarized tabular form. Documented case reports of herbs or dietary supplements (DS; includes herbs) appearing to contribute to liver injury were used to create an online "DS Toxic Table" of potentially hepatotoxic herbs and dietary supplements (PubMed, 1966 to June, 2016, and cross-referencing). The spectrum of DS induced liver injuries (DSILI) included elevated liver enzymes, hepatitis, steatosis, cholestasis, hepatic necrosis, hepatic fibrosis, hepatic cirrhosis, veno-occlusive disease, acute liver failure requiring a liver transplant, and death. Over the past 50 years, approximately 21 herbs (minus germander and usnic acid that are no longer sold) and 12 dietary supplements (minus the nine no longer sold and vitamin A & niacin due to excess intake) posed a possible risk for liver injures in certain individuals. The herbs with the most number of reported publications (but not cases studies) in descending order, were germander, black cohosh, kava extract, and green tea extract. These online DS Toxic Tables will contribute to continued Phase IV post marketing surveillance to detect possible liver toxicity cases and serve to forewarn consumers, clinicians, and corporations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Porcine foetal and neonatal CYP3A liver expression

    DEFF Research Database (Denmark)

    Hermann-Bank, Marie Louise; Skaanild, Mette Tingleff

    2011-01-01

    enzyme in the foetal liver, whereas the expression of CYP3A4 is low. After parturition there is a shift in the expression, thus CYP3A7 is down regulated, while the level of CYP3A4 gradually increases and becomes the dominant metabolising CYP3A enzyme in the adult. The minipig is increasingly being used......3A4) in minipigs. This was elucidated by examining the hepatic mRNA expression of CYP3A7 and CYP3A29 in 39 foetuses and newborn Göttingen minipigs using quantitative real time polymerase chain reaction (qPCR). Furthermore the immunochemical level of CYP3A7-LE and CYP3A29 was measured in liver...

  19. Kynureninase-type enzymes and the evolution of the aerobic tryptophan-to-nicotinamide adenine dinucleotide pathway

    Energy Technology Data Exchange (ETDEWEB)

    Gaertner, F.H.; Shetty, A.S.

    1977-01-01

    Kynureninase-type (L-kynurenine hydrolase, EC 3.7.1.3) activity has been found to be present in the livers of fish, amphibia, reptiles, and birds. In addition to past information concerning this enzyme activity in mammalian liver, it is now clear that all the major classes of vertebrates carry a highly specialized kynureninase-type enzyme, which we have termed a hydroxykynureninase. To compare the reactivities of these enzymes with L-kynurenine and L-3-hydroxykynurenine, ratios of tau values (K/sub m//V) were used. Based on this comparison, the bacterium Pseudomonas fluorescens carries the most efficient kynureninase, whereas the amphibian Xenopus laevis has the most efficient hydroxykynurenase. In these two cases, the ratio of tau values differs by a factor of 38,000. It is hypothesized that the tryptophan-to-nicotinamide adenine dinucleotide biosynthetic pathway evolved from a catabolic system of enzymes, and that the differences observed in the kynureninase-type enzymes between lower and higher organisms reflect the specialization of the function of these enzymes from a strictly catabolic role to an anabolic one during the course of evolution.

  20. Induction of Morphological Changes in Human Embryo Liver Cells by the Pyrrolizidine Alkaloid Lasiocarpine

    Science.gov (United States)

    Armstrong, Sylvia J.; Zuckerman, A. J.; Bird, R. G.

    1972-01-01

    The pyrrolizidine alkaloids have been implicated in the aetiology of liver disease in man and in animals. Studies of the effects of lasiocarpine indicate that they have several and perhaps independent effects on human liver cells in culture. These may be summarized as follows: 1. Nuclear and nucleolar changes which are probably related to the alkylation of DNA and ensuing inhibition of nucleic acid and protein synthesis. 2. The induction of possible chromosomal damage and mutation. 3. A generalized reduction of the metabolic activities of the cells due to membrane and mitochondrial damage, and to alkylation and inactivation of cell enzymes and proteins. 4. A long-term inhibition of mitosis leading to the formation of giant cells (“megalocytes”). The morphological effects induced by a number of the pyrrolizidine alkaloids were very similar but the pattern of metabolic changes varied somewhat. It is believed that the hepatotoxic effects are not due to the pyrrolizidine alkaloids themselves but to metabolic derivatives formed by the cell. ImagesFigs. 3-5Figs. 1-2 PMID:5032090

  1. Presentation of an acquired urea cycle disorder post liver transplantation.

    Science.gov (United States)

    Ghabril, Marwan; Nguyen, Justin; Kramer, David; Genco, Trina; Mai, Martin; Rosser, Barry G

    2007-12-01

    The liver's role as the largest organ of metabolism and the unique and often critical function of liver-specific enzyme pathways imply a greater risk to the recipient of acquiring a donor metabolic disease with liver transplants versus other solid organ transplants. With clinical consequences rarely reported, the frequency of solid organ transplant transfer of metabolic disease is not known. Ornithine transcarbamylase deficiency (OTCD), although rare, is the most common of the urea cycle disorders (UCDs). Because of phenotypic heterogeneity, OTCD may go undiagnosed into adulthood. With over 5000 liver transplant procedures annually in the United States, the likelihood of unknowingly transmitting OTCD through liver transplantation is very low. We describe the clinical course of a liver transplant recipient presenting with acute hyperammonemia and encephalopathy after receiving a liver graft form a donor with unrecognized OTCD. Copyright (c) 2007 AASLD.

  2. Biliary-duodenal anastomosis using magnetic compression following massive resection of small intestine due to strangulated ileus after living donor liver transplantation: a case report.

    Science.gov (United States)

    Saito, Ryusuke; Tahara, Hiroyuki; Shimizu, Seiichi; Ohira, Masahiro; Ide, Kentaro; Ishiyama, Kohei; Kobayashi, Tsuyoshi; Ohdan, Hideki

    2017-12-01

    Despite the improvements of surgical techniques and postoperative management of patients with liver transplantation, biliary complications are one of the most common and important adverse events. We present a first case of choledochoduodenostomy using magnetic compression following a massive resection of the small intestine due to strangulated ileus after living donor liver transplantation. The 54-year-old female patient had end-stage liver disease, secondary to liver cirrhosis, due to primary sclerosing cholangitis with ulcerative colitis. Five years earlier, she had received living donor liver transplantation using a left lobe graft, with resection of the extrahepatic bile duct and Roux-en-Y anastomosis. The patient experienced sudden onset of intense abdominal pain. An emergency surgery was performed, and the diagnosis was confirmed as strangulated ileus due to twisting of the mesentery. Resection of the massive small intestine, including choledochojejunostomy, was performed. Only 70 cm of the small intestine remained. She was transferred to our hospital with an external drainage tube from the biliary cavity and jejunostomy. We initiated total parenteral nutrition, and percutaneous transhepatic biliary drainage was established to treat the cholangitis. Computed tomography revealed that the biliary duct was close to the duodenum; hence, we planned magnetic compression anastomosis of the biliary duct and the duodenum. The daughter magnet was placed in the biliary drainage tube, and the parent magnet was positioned in the bulbus duodeni using a fiberscope. Anastomosis between the left hepatic duct and the duodenum was accomplished after 25 days, and the biliary drainage stent was placed over the anastomosis to prevent re-stenosis. Contributions to the successful withdrawal of parenteral nutrition were closure of the ileostomy in the adaptive period, preservation of the ileocecal valve, internal drainage of bile, and side-to-side anastomosis

  3. Influence of nutrition on liver oxidative metabolism.

    Science.gov (United States)

    Jorquera, F; Culebras, J M; González-Gallego, J

    1996-06-01

    The liver plays a major role in the disposition of the majority of drugs. This is due to the presence of several drug-metabolizing enzyme systems, including a group of membrane-bound mixed-function oxidative enzymes, mainly the cytochrome P450 system. Hepatic oxidative capacity can be assessed by changes in antipyrine metabolism. Different drugs and other factors may induce or inhibit the cytochrome P450-dependent system. This effect is important in terms of the efficacy or toxicity of drugs that are substrates for the system. Microsomal oxidation in animals fed with protein-deficient diets is depressed. The mixed-function oxidase activity recovers after a hyperproteic diet or the addition of lipids. Similar findings have been reported in patients with protein-calorie malnutrition, although results in the elderly are conflicting. Different studies have revealed that microsomal oxidation is impaired by total parenteral nutrition and that this effect is absent when changing the caloric source from carbohydrates to a conventional amino acid solution or after lipid addition, especially when administered as medium-chain/long-chain triglyceride mixtures. Peripheral parenteral nutrition appears to increase antipyrine clearance.

  4. A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions.

    Science.gov (United States)

    Cherkaoui-Rbati, Mohammed H; Paine, Stuart W; Littlewood, Peter; Rauch, Cyril

    2017-01-01

    All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs) of new chemical entities (NCEs) and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that the liver is a homogeneous organ where the majority of the metabolism occurs. However, the circulatory system of the liver has a complex hierarchical geometry which distributes xenobiotics throughout the organ. Nevertheless, the lobule (liver unit), located at the end of each branch, is composed of many sinusoids where the blood flow can vary and therefore creates heterogeneity (e.g. drug concentration, enzyme level). A liver model was constructed by describing the geometry of a lobule, where the blood velocity increases toward the central vein, and by modeling the exchange mechanisms between the blood and hepatocytes. Moreover, the three major DDI mechanisms of metabolic enzymes; competitive inhibition, mechanism based inhibition and induction, were accounted for with an undefined number of drugs and/or enzymes. The liver model was incorporated into a physiological-based pharmacokinetic (PBPK) model and simulations produced, that in turn were compared to ten clinical results. The liver model generated a hierarchy of 5 sinusoidal levels and estimated a blood volume of 283 mL and a cell density of 193 × 106 cells/g in the liver. The overall PBPK model predicted the pharmacokinetics of midazolam and the magnitude of the clinical DDI with perpetrator drug(s) including spatial and temporal enzyme levels changes. The model presented herein may reduce costs and the use of laboratory animals and give the opportunity to explore different clinical scenarios, which reduce the risk of adverse events, prior to costly human clinical studies.

  5. A quantitative systems pharmacology approach, incorporating a novel liver model, for predicting pharmacokinetic drug-drug interactions.

    Directory of Open Access Journals (Sweden)

    Mohammed H Cherkaoui-Rbati

    Full Text Available All pharmaceutical companies are required to assess pharmacokinetic drug-drug interactions (DDIs of new chemical entities (NCEs and mathematical prediction helps to select the best NCE candidate with regard to adverse effects resulting from a DDI before any costly clinical studies. Most current models assume that the liver is a homogeneous organ where the majority of the metabolism occurs. However, the circulatory system of the liver has a complex hierarchical geometry which distributes xenobiotics throughout the organ. Nevertheless, the lobule (liver unit, located at the end of each branch, is composed of many sinusoids where the blood flow can vary and therefore creates heterogeneity (e.g. drug concentration, enzyme level. A liver model was constructed by describing the geometry of a lobule, where the blood velocity increases toward the central vein, and by modeling the exchange mechanisms between the blood and hepatocytes. Moreover, the three major DDI mechanisms of metabolic enzymes; competitive inhibition, mechanism based inhibition and induction, were accounted for with an undefined number of drugs and/or enzymes. The liver model was incorporated into a physiological-based pharmacokinetic (PBPK model and simulations produced, that in turn were compared to ten clinical results. The liver model generated a hierarchy of 5 sinusoidal levels and estimated a blood volume of 283 mL and a cell density of 193 × 106 cells/g in the liver. The overall PBPK model predicted the pharmacokinetics of midazolam and the magnitude of the clinical DDI with perpetrator drug(s including spatial and temporal enzyme levels changes. The model presented herein may reduce costs and the use of laboratory animals and give the opportunity to explore different clinical scenarios, which reduce the risk of adverse events, prior to costly human clinical studies.

  6. Livers from fasted rats acquire resistance to warm and cold ischemia injury.

    Science.gov (United States)

    Sumimoto, R; Southard, J H; Belzer, F O

    1993-04-01

    Successful liver transplantation is dependent upon many factors, one of which is the quality of the donor organ. Previous studies have suggested that the donor nutritional status may affect the outcome of liver transplantation and starvation, due to prolonged stay in the intensive care unit, may adversely affect the liver. In this study we have used the orthotopic rat liver transplant model to measure how fasting the donor affects the outcome of liver transplantation. Rat livers were preserved with UW solution either at 37 degrees C (warm ischemia for 45-60 min) or at 4 degrees C (cold ischemia for 30 or 44 hr). After preservation the livers were orthotopically transplanted and survival (for 7 days) was measured, as well as liver functions 6 hr after transplantation. After 45 min of warm ischemia 50% (3 of 6) animals survived when the liver was obtained from a fed donor about 80% (4 of 5) survived when the liver was obtained from a three-day-fasted donor. After 60 min warm ischemia no animal survived (0 of 8, fed group). However, if the donor was fasted for 3 days 89% (8 of 9) of the animals survived for 7 days. Livers cold-stored for 30 hr were 50% viable (3 of 6) and fasting for 1-3 days did not affect this outcome. However, if the donor was fasted for 4 days 100% (9 of 9) survival was obtained. After 44-hr preservation only 29% (2/7) of the recipients survived for 7 days. If the donor was fasted for 4 days, survival increased to 83% (5/6). Liver functions, bile production, and serum enzymes were better in livers from the fasted rats than from the fed rats. Fasting caused a 95% decrease in liver glycogen content. Even with this low concentration of glycogen, liver viability (animal survival) after warm or cold ischemia was not affected, and livers with a low glycogen content were fully viable. Thus liver glycogen does not appear to be important in liver preservation. This study shows that fasting the donor does not cause injury to the liver after warm or cold

  7. The Effect of Tobacco Snuff Consumption on Liver Enzymes | Ugbor ...

    African Journals Online (AJOL)

    This study was designed to investigate the changes in liver biochemical profile following oral tobacco dust ingestion. Adult Wistar rats (42) weighing 150-300g were involved. They were divided into four groups; group A serving as control, while groups B, C and D served as the test groups. The test groups were further ...

  8. Fructose effect to enhance liver glycogen deposition is due to inhibition of glycogenolysis

    International Nuclear Information System (INIS)

    Youn, J.; Kaslow, H.; Bergman, R.

    1987-01-01

    The effect of fructose on glycogen degradation was examined by measuring flux of [ 14 C] from prelabeled glycogen in perfused rat livers. During 2 h refeeding of fasted rats hepatic glycogen was labeled by injection of [U 14 C] galactose (0.1 mg and 0.02 μCi/g of body weight). Refed livers were perfused for 30 min with glucose only (10 mM) and for 60 min with glucose (10 mM) without (n=5) or with fructose (1, 2, 10 mM; n=5 for each). With fructose, label production immediately declined and remained suppressed through the end of perfusion (P < 0.05). Suppression was dose-dependent: steady state label production was suppressed 45, 64, and 72% by 1, 2, and 10 mM fructose (P < 0.0001), without significant changes in glycogen synthase or phosphorylase. These results suggest the existence of allosteric inhibition of phosphorylase in the presence of fructose. Fructose 1-phosphate (F1P) accumulated in proportion to fructose (0.11 +/- 0.01 without fructose, 0.86 +/- 0.03, 1.81 +/- 0.18, and 8.23 +/- 0.6 μmoles/g of liver with 1, 2, and 10 mM fructose. Maximum inhibition of phosphorylase was 82%; FIP concentration for half inhibition was 0.57 μmoles/g of liver, well within the concentration of F1P attained in refeeding. Fructose enhances net glycogen synthesis in liver by suppressing glycogenolysis and the suppression is presumably caused by allosteric inhibition of phosphorylase by F1P

  9. Impairment of liver and kidney functions in gamma irradiation rats suffering pesticide toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Roushdy, H M; Abdel-Hamid, F M; Abu-Ghadir, A R [Radiation biology department, National Centre for Radiation Research and Technology, Radio isotope Department, Nuclear Reseach Center, and atomic Energy, Authority, Cairo (Egypt)

    1995-10-01

    The effect of exposure to single whole body gamma irradiation dose at 6.5 Gy and/or either oral administration of 50 or 100 mg kelthane/kg kelthane/kg body weight/day for successively 3 days, or daily feeding with 200 mg kelthane/kg body weight for 3, 6, and 12 weeks has been studied on relative liver and kidney weights, certain serum and liver enzymes creatinine and inorganic phosphorous clearance, as well as percentage of tubular phosphorous reabsorption in male animals. The data obtained revealed that exposure to gamma-irradiation alone or combined with kelthane treatment caused significant increase in the relative spleen weight besides significant decrease in serum and liver alkaline phosphatase and serum cholinesterase. Exposure to gamma irradiation after orally administration of 100 mg or feeding dietary kelthane caused significant decrease in liver glucose-6-phosphatase. Non significant changes in aspartic and alanine transaminases could be recorded due to gamma-irradiation and/or kelthane treatment. Endogenous clearance of creatinine and phosphorous as well as tubular phosphorous reabsorption were determined to assess the glomerular filtration and tubular function. The data obtained revealed that exposure to gamma-irradiation either alone or after treatment with kelthane caused significant decrease in creatinine and phosphorous clearance while phosphorous reabsorption was not appreciably affected. 4 tabs.

  10. Impairment of liver and kidney functions in gamma irradiation rats suffering pesticide toxicity

    International Nuclear Information System (INIS)

    Roushdy, H.M.; Abdel-Hamid, F.M.; Abu-Ghadir, A.R.

    1995-01-01

    The effect of exposure to single whole body gamma irradiation dose at 6.5 Gy and/or either oral administration of 50 or 100 mg kelthane/kg kelthane/kg body weight/day for successively 3 days, or daily feeding with 200 mg kelthane/kg body weight for 3, 6, and 12 weeks has been studied on relative liver and kidney weights, certain serum and liver enzymes creatinine and inorganic phosphorous clearance, as well as percentage of tubular phosphorous reabsorption in male animals. The data obtained revealed that exposure to gamma-irradiation alone or combined with kelthane treatment caused significant increase in the relative spleen weight besides significant decrease in serum and liver alkaline phosphatase and serum cholinesterase. Exposure to gamma irradiation after orally administration of 100 mg or feeding dietary kelthane caused significant decrease in liver glucose-6-phosphatase. Non significant changes in aspartic and alanine transaminases could be recorded due to gamma-irradiation and/or kelthane treatment. Endogenous clearance of creatinine and phosphorous as well as tubular phosphorous reabsorption were determined to assess the glomerular filtration and tubular function. The data obtained revealed that exposure to gamma-irradiation either alone or after treatment with kelthane caused significant decrease in creatinine and phosphorous clearance while phosphorous reabsorption was not appreciably affected. 4 tabs

  11. Acetaldehyde Adducts in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Mashiko Setshedi

    2010-01-01

    Full Text Available Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD, with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC. Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15% versus cirrhosis (15–20% is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.

  12. Epoxidation of the methamphetamine pyrolysis product, trans-phenylpropene, to trans-phenylpropylene oxide by CYP enzymes and stereoselective glutathione adduct formation

    International Nuclear Information System (INIS)

    Sanga, Madhu; Younis, Islam R.; Tirumalai, Padma S.; Bland, Tina M.; Banaszewska, Monica; Konat, Gregory W.; Tracy, Timothy S.; Gannett, Peter M.; Callery, Patrick S.

    2006-01-01

    Pyrolytic products of smoked methamphetamine hydrochloride are well established. Among the various degradation products formed, trans-phenylpropene (trans-β-methylstyrene) is structurally similar to styrene analogues known to be bioactivated by CYP enzymes. In human liver microsomes, trans-phenylpropene was converted to the epoxide trans-phenylpropylene oxide (trans-2-methyl-3-phenyloxirane) and cinnamyl alcohol. Incubation of trans-phenylpropene with microsomes in the presence of enzyme-specific P450 enzyme inhibitors indicated the involvement of CYP2E1, CYP1A2, and CYP3A4 enzymes. Both (R,R)-phenylpropylene oxide and (S,S)-phenylpropylene oxide were formed in human liver microsomal preparations. Enantiomers of trans-phenylpropylene oxide were stereoselectively and regioselectively conjugated in a Phase II drug metabolism reaction catalyzed by human liver cytosolic enzymes consisting of conjugation with glutathione. The structure of the phenylpropylene oxide-glutathione adduct is consistent with nucleophilic ring-opening by attack at the benzylic carbon. Exposure of cultured C6 glial cells to (S,S)-phenylpropylene oxide produced a cytotoxic response in a concentration-dependent manner based on cell degeneration and death

  13. Deoxynucleoside salvage enzymes and tissue specific mitochondrial DNA depletion.

    Science.gov (United States)

    Wang, L

    2010-06-01

    Adequate mitochondrial DNA (mtDNA) copies are required for normal mitochondria function and reductions in mtDNA copy number due to genetic alterations cause tissue-specific mtDNA depletion syndrome (MDS). There are eight nuclear genes, directly or indirectly involved in mtDNA replication and mtDNA precursor synthesis, which have been identified as the cause of MDS. However, the tissue specific pathology of these nuclear gene mutations is not well understood. Here, mtDNA synthesis, mtDNA copy number control, and mtDNA turnover, as well as the synthesis of mtDNA precursors in relation to the levels of salvage enzymes are discussed. The question why MDS caused by TK2 and p53R2 mutations are predominantly muscle specific while dGK deficiency affected mainly liver will be addressed.

  14. Computer tomographic findings in portal hypertension due to cirrhosis of the liver. Pt. 2

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, P; Koester, O; Lackner, K; Kunz, R; Koischwitz, D

    1983-07-01

    The results of a discriminant analysis for the objective diagnosis of cirrhosis of the liver are reported. Eight quantitative parameters seen on CT which, by themselves, are not diagnostic, were studied, and three relationships found to be of discriminatory significance; they are the diameter of the superior mesenteric vein, the ratio of the diameter of the caudate lobe and the right lobe of the liver and a quotient derived from the splenic and hepatic index. Cirrhosis of the liver with portal hypertension could be distinguished with a specificity of 100%, an accuracy of 96% and a sensitivity of 94%.

  15. Computer tomographic findings in portal hypertension due to cirrhosis of the liver. Pt. 2

    International Nuclear Information System (INIS)

    Fischer, P.; Koester, O.; Lackner, K.; Kunz, R.; Koischwitz, D.

    1983-01-01

    The results of a discriminant analysis for the objective diagnosis of cirrhosis of the liver are reported. Eight quantitative parameters seen on CT which, by themselves, are not diagnostic, were studied, and three relationships found to be of discriminatory significance; they are the diameter of the superior mesenteric vein, the ratio of the diameter of the caudate lobe and the right lobe of the liver and a quotient derived from the splenic and hepatic index. Cirrhosis of the liver with portal hypertension could be distinguished with a specificity of 100%, an accuracy of 96% and a sensitivity of 94%. (orig.) [de

  16. Energy Metabolism in the Liver

    Science.gov (United States)

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic activity is tightly controlled by insulin and other metabolic hormones. Glucose is metabolized into pyruvate through glycolysis in the cytoplasm, and pyruvate is completely oxidized to generate ATP through the TCA cycle and oxidative phosphorylation in the mitochondria. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and cholesterol esters in hepatocytes, and these complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as VLDL particles. In the fasted state, the liver secretes glucose through both breakdown of glycogen (glycogenolysis) and de novo glucose synthesis (gluconeogenesis). During pronged fasting, hepatic gluconeogenesis is the primary source of endogenous glucose production. Fasting also promotes lipolysis in adipose tissue to release nonesterified fatty acids which are converted into ketone bodies in the liver though mitochondrial β oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver metabolic processes are tightly regulated by neuronal and hormonal systems. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis, but suppresses gluconeogenesis; glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze the rate-limiting steps of liver metabolic processes, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD). PMID:24692138

  17. When the heart kills the liver: acute liver failure in congestive heart failure

    Directory of Open Access Journals (Sweden)

    Saner FH

    2009-12-01

    Full Text Available Abstract Congestive heart failure as a cause of acute liver failure is rarely documented with only a few cases. Although the pathophysiology is poorly understood, there is rising evidence, that low cardiac output with consecutive reduction in hepatic blood flow is a main causing factor, rather than hypotension. In the setting of acute liver failure due to congestive heart failure, clinical signs of the latter can be absent, which requires an appropriate diagnostic approach. As a reference center for acute liver failure and liver transplantation we recorded from May 2003 to December 2007 202 admissions with the primary diagnoses acute liver failure. 13/202 was due to congestive heart failure, which was associated with a mortality rate of 54%. Leading cause of death was the underlying heart failure. Asparagine transaminase (AST, bilirubin, and international normalized ratio (INR did not differ significantly in surviving and deceased patients at admission. Despite both groups had signs of cardiogenic shock, the cardiac index (CI was significantly higher in the survival group on admission as compared with non-survivors (2.1 L/min/m2 vs. 1.6 L/min/m2, p = 0.04. Central venous - and pulmonary wedge pressure did not differ significantly. Remarkable improvement of liver function was recorded in the group, who recovered from cardiogenic shock. In conclusion, patients with acute liver failure require an appropriate diagnostic approach. Congestive heart failure should always be considered as a possible cause of acute liver failure.

  18. Effect of oral D-tagatose on liver volume and hepatic glycogen accumulation in healthy male volunteers.

    Science.gov (United States)

    Boesch, C; Ith, M; Jung, B; Bruegger, K; Erban, S; Diamantis, I; Kreis, R; Bär, A

    2001-04-01

    Standard toxicity tests with high levels of D-tagatose showed a reversible enlargement of the liver in Sprague-Dawley rats without increase of liver enzymes. The present study tests the hypotheses that partial substitution of dietary sucrose by D-tagatose for 28 days increases the volume of human liver and the concentration of liver glycogen. Twelve healthy, male volunteers were studied in a double-blind crossover study with ingestion of D-tagatose (3x15 g daily) and placebo (sucrose, 3x15 g daily) for periods of 28 days each. Liver volume and glycogen concentration have been determined by magnetic resonance (MR) imaging and spectroscopy, which were accompanied by routine medical examinations. MR examinations before and after the treatments revealed no effects (P>0.05) of treatment, period, or subject for changes in liver volume or glycogen concentration. A steady increase of liver volumes, independent of the D-tagatose or placebo intake, has been observed over the study in parallel with a slight increase in body weight. The treatment with D-tagatose was not associated with clinically relevant changes of the examined clinico-chemical and hematological parameters, including liver enzymes and uric acid. Copyright 2001 Academic Press.

  19. The long-term hemodynamic changes of liver and spleen after partial splenic embolization for portal hypertension due to cirrhosis

    International Nuclear Information System (INIS)

    Zhang Xinyuan; Geng Huijie; Wang Baocai; Zhang Xinfang; Du Ruiqing; Wang Lijing; Yin Shumei

    2009-01-01

    Objective: To observe the long-term hemodynamic changes of liver and spleen after partial splenic embolization (PSE) in patients with portal hypertension due to cirrhosis. Methods: PSE was performed in 1720 patients with portal hypertension and hypersplenism due to cirrhosis. The survival rate of 1 - 5 years and the cause of death were observed. The preoperative and postoperative hemodynamics of both the liver and spleen, the blood picture, splenic size and the complications in 600 patients who survived over five years and had integrated document were retrospectively analyzed and compared. Results Obvious changes in hemodynamics at different time after PSE were seen. The frequency and the volume of gastrointestinal bleeding were obviously decreased, while the leucocyte and platelet count was markedly increased. The spleen size began to reduce two months after PSE, which became very obvious in three months. The difference in above items between pre-PSE and post-PSE was statistically significant (P < 0.01). Conclusion: PSE can definitely improve hepatic and splenic hemodynamics, reduce the pressure of portal vein, alleviate hypersplenism and reduce the occurrence of gastrointestinal bleeding, elongate the life span and improve the living quality. With obvious and reliable long-term efficacy and fewer complications, PSE is a minimallyinvasive, safe and effective therapy. (authors)

  20. Delayed liver regeneration after partial hepatectomy in adiponectin knockout mice

    International Nuclear Information System (INIS)

    Ezaki, Hisao; Yoshida, Yuichi; Saji, Yukiko; Takemura, Takayo; Fukushima, Juichi; Matsumoto, Hitoshi; Kamada, Yoshihiro; Wada, Akira; Igura, Takumi; Kihara, Shinji; Funahashi, Tohru; Shimomura, Iichiro; Tamura, Shinji; Kiso, Shinichi; Hayashi, Norio

    2009-01-01

    We previously demonstrated that adiponectin has anti-fibrogenic and anti-inflammatory effects in the liver of mouse models of various liver diseases. However, its role in liver regeneration remains unclear. The aim of this study was to determine the role of adiponectin in liver regeneration. We assessed liver regeneration after partial hepatectomy in wild-type (WT) and adiponectin knockout (KO) mice. We analyzed DNA replication and various signaling pathways involved in cell proliferation and metabolism. Adiponectin KO mice exhibited delayed DNA replication and increased lipid accumulation in the regenerating liver. The expression levels of peroxisome proliferator-activated receptor (PPAR) α and carnitine palmitoyltransferase-1 (CPT-1), a key enzyme in mitochondrial fatty acid oxidation, were decreased in adiponectin KO mice, suggesting possible contribution of altered fat metabolism to these phenomena. Collectively, the present results highlight a new role for adiponectin in the process of liver regeneration.

  1. Human liver segments: role of cryptic liver lobes and vascular physiology in the development of liver veins and left-right asymmetry

    NARCIS (Netherlands)

    Hikspoors, Jill P. J. M.; Peeters, Mathijs M. J. P.; Kruepunga, Nutmethee; Mekonen, Hayelom K.; Mommen, Greet M. C.; Köhler, S. Eleonore; Lamers, Wouter H.

    2017-01-01

    Couinaud based his well-known subdivision of the liver into (surgical) segments on the branching order of portal veins and the location of hepatic veins. However, both segment boundaries and number remain controversial due to an incomplete understanding of the role of liver lobes and vascular

  2. Polyphenols of Salix aegyptiaca modulate the activities of drug metabolizing and antioxidant enzymes, and level of lipid peroxidation.

    Science.gov (United States)

    Nauman, Mohd; Kale, R K; Singh, Rana P

    2018-03-07

    Salix aegyptiaca is known for its medicinal properties mainly due to the presence of salicylate compounds. However, it also contains other beneficial phytochemicals such as gallic acid, quercetin, rutin and vanillin. The aim of the study was to examine the redox potential, antioxidant and anti-inflammatory activity of these phytochemicals along with acetylsalicylic acid. The redox potential and antioxidant activity of gallic acid, quercetin, rutin, vanillin and acetylsalicylic acid were determined by oxidation-reduction potential electrode method and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, respectively. In ex vivo studies, antioxidant activity of these phytochemicals was determined by lipid peroxidation and carbonyl content assay in the liver of mice. Anti-inflammatory activity was determined by protein denaturation method. Six-week old C57BL/6 mice treated with gallic acid (100 mg/kg body weight) and acetylsalicylic acid (25 and 50 mg/kg body weight) to investigate their in vivo modulatory effects on the specific activities of drug metabolizing phase I and phase II enzymes, antioxidant enzymes and level of lipid peroxidation in liver. The order of ability to donate electron and antioxidant activity was found to be: gallic acid > quercetin > rutin > vanillin > acetylsalicylic acid. In ex vivo studies, the similar pattern and magnitude of inhibitory effects of these phytochemicals against peroxidative damage in microsomes and protein carbonyl in cytosolic fraction were observed. In in vivo studies, gallic acid and acetylsalicylic acid alone or in combination, enhanced the specific activities of drug metabolizing phase I and phase II enzymes as well as antioxidant enzymes and also inhibited lipid peroxidation in liver. These findings show a close link between the electron donation and antioxidation potential of these phytochemicals, and in turn their biological activity. Gallic acid, quercetin, rutin and vanillin were found to be better electron donors and

  3. Possible gasoline-induced chronic liver injury due to occupational malpractice in a motor mechanic: a case report

    OpenAIRE

    Gunathilaka, Mahesh Lakmal; Niriella, Madunil Anuk; Luke, Nathasha Vihangi; Piyarathna, Chathura Lakmal; Siriwardena, Rohan Chaminda; De Silva, Arjuna Priyadarshin; de Silva, Hithanadura Janaka

    2017-01-01

    Background Hydrocarbon-induced occupational liver injury is a well-known clinical entity among petroleum industry workers. There are many types of hydrocarbon exposure, with inhalation being the most common. Hydrocarbon-induced occupational liver injury is a rarely suspected and commonly missed etiological agent for liver injury. We report a case of a non-petroleum industry worker with chronic liver disease secondary to hydrocarbon-induced occupational liver injury caused by chronic low-grade...

  4. MicroRNAs as Biomarkers for Liver Disease and Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    C. Nelson Hayes

    2016-02-01

    Full Text Available Serum levels of liver enzymes, such as alanine transaminase, aspartate transaminase, and α-fetoprotein, provide insight into liver function and are used during treatment of liver disease, but such information is limited. In the case of hepatocellular carcinoma (HCC, which is often not detected until an advanced stage, more sensitive biomarkers may help to achieve earlier detection. Serum also contains microRNAs, a class of small non-coding RNAs that play an important role in regulating gene expression. miR-122 is specific to the liver and correlates strongly with liver enzyme levels and necroinflammatory activity, and other microRNAs are correlated with the degree of fibrosis. miR-122 has also been found to be required for hepatitis C virus (HCV infection, whereas other microRNAs have been shown to play antiviral roles. miR-125a-5p and miR-1231 have been shown to directly target hepatitis B virus (HBV transcripts, and others are up- or down-regulated in infected individuals. MicroRNA profiles also differ in the case of HBV and HCV infection as well as between HBeAg-positive and negative patients, and in patients with occult versus active HBV infection. In such patients, monitoring of changes in microRNA profiles might provide earlier warning of neoplastic changes preceding HCC.

  5. Ultrastructural Changes in the Liver of Intravenous Heroin Addicts

    Directory of Open Access Journals (Sweden)

    Goran Ilić

    2010-02-01

    Full Text Available The ultrastructural research has a decisive role in gathering the knowledge on the liver’s response to the influence of some drugs. The aim of the study was to perform an ultrastructurai analysis of the liver in chronic intravenous heroin addicts.The study involved the autopsy conducted on 40 bodies of intravenous heroin addicts and 10 control autopsies. The liver tissue was fixed in glutaraldehyde and moulded with epon for investigation purposes of ultrastructural changes. The analysis was performed using the method of transmission electron microscopy.In the group of intravenous heroin addicts, the liver autopsy samples showed degenerative vesicular and fat changes, chronic active and persistent hepatitis, cirrhosis, reduction in the amount of glycogen in hepatocytes, as well as the Kupffer cell’s dominant hypertrophy. Various changes occur in organelles, plasma membrane of hepatocytes and biliary channels as well as in the nucleus.The most important ultrastructural findings include: hyperplasia and hypertrophy of the smooth endoplasmic reticulum, which is histologically proven vesicular degeneration of hepatocyte occurring as a result of the increased synthesis of enzymes of smooth endoplasmic reticulum due to chronic intravenous heroin intake, and the presence of continuous basal membrane followed by transformation of the sinusoids into capillaries (in the cases of chronic active hepatitis and cirrhosis which leads to a disorder of microcirculation and further progress of cirrhosis.

  6. In vitro biotransformation of tris(2-butoxyethyl) phosphate (TBOEP) in human liver and serum

    Energy Technology Data Exchange (ETDEWEB)

    Van den Eede, Nele, E-mail: nele.vandeneede@uantwerpen.be [Toxicological Center, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp (Belgium); Erratico, Claudio [Toxicological Center, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp (Belgium); Exarchou, Vassiliki [Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp (Belgium); Maho, Walid; Neels, Hugo [Toxicological Center, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp (Belgium); Covaci, Adrian, E-mail: adrian.covaci@uantwerpen.be [Toxicological Center, Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp (Belgium)

    2015-04-15

    Tris(2-butoxyethyl) phosphate (TBOEP) is a plasticizer present in indoor dust, reaching levels of several micrograms per gram. Such levels could lead to significant daily exposure of adults and children. Currently, no toxicokinetic data are available to estimate TBOEP clearance in humans after uptake and therefore, one objective of this study was to investigate intrinsic clearance of TBOEP by human liver microsome (HLM) and serum enzymes. Another objective was to generate information to identify and prioritize several metabolites of TBOEP for investigation of human exposure by biomonitoring. 1D and 2D-NMR methodologies were successfully applied on a mixture of the metabolites to confirm the structure of 3-HO-TBOEP (bis(2-butoxyethyl) 3-hydroxyl-2-butoxyethyl phosphate) and to tentatively assign structures to 1-HO-TBOEP and 2-HO-TBOEP. HO-TBOEP isomers and bis(2-butoxyethyl) phosphate (BBOEP), bis(2-butoxyethyl) hydroxyethyl phosphate (BBOEHEP) were further monitored by liquid chromatography–tandem mass spectrometry. Rates of formation of BBOEHEP and HO-TBOEP metabolites by liver enzymes were best described by the Michaelis–Menten model. Apparent K{sub m} values for BBOEHEP, 3-HO-TBOEP, and sum of 1- and 2-HO-TBOEP isomer formation were 152, 197 and 148 μM, respectively. Apparent V{sub max} values for the formation of BBOEHEP, 3-HO-TBOEP, and the sum of 1- and 2-HO-TBOEP isomers were 2560, 643, and 254 pmol/min/mg protein, respectively. No detectable formation of BBOEP occurred with liver or serum enzymes. Our findings indicate that intrinsic clearance of TBOEP is mainly catalyzed by oxidative enzymes in the liver and that its major in vitro metabolite is BBOEHEP. These findings can be applied in human biomonitoring studies and risk assessment. - Highlights: • First steps in the elucidation of TBOEP toxicokinetics • Quantification of TBOEP metabolites in human serum and liver microsomes • No detectable formation of BBOEP occurred with liver or serum

  7. Radiation-induced liver damage

    International Nuclear Information System (INIS)

    Marcial, V.A.; Santiago-Delpin, E.A.; Lanaro, A.E.; Castro-Vita, H.; Arroyo, G.; Moscol, J.A.; Gomez, C.; Velazquez, J.; Prado, K.

    1977-01-01

    Due to the recent increase in the use of radiation therapy in the treatment of cancer with or without chemotherapy, the risk of liver radiation damage has become a significant concern for the radiotherapist when the treated tumour is located in the upper abdomen or lower thorax. Clinically evident radiation liver damage may result in significant mortality, but at times patients recover without sequelae. The dose of 3000 rads in 3 weeks to the entire liver with 5 fractions per week of 200 rads each, seems to be tolerated well clinically by adult humans. Lower doses may lead to damage when used in children, when chemotherapy is added, as in recent hepatectomy cases, and in the presence of pre-existent liver damage. Reduced fractionation may lead to increased damage. Increased fractionation, limitation of the dose delivered to the entire liver, and restriction of the high dose irradiation volume may afford protection. With the aim of studying the problems of hepatic radiation injury in humans, a project of liver irradiation in the dog is being conducted. Mongrel dogs are being conditioned, submitted to pre-irradiation studies (haemogram, blood chemistry, liver scan and biopsy), irradiated under conditions resembling human cancer therapy, and submitted to post-irradiation evaluation of the liver. Twenty-two dogs have been entered in the study but only four qualify for the evaluation of all the study parameters. It has been found that dogs are susceptible to liver irradiation damage similar to humans. The initial mortality has been high mainly due to non-radiation factors which are being kept under control at the present phase of the study. After the initial experiences, the study will involve variations in total dose and fractionation, and the addition of anticoagulant therapy for possible prevention of radiation liver injury. (author)

  8. Sex-specific metabolic interactions between liver and adipose tissue in MCD diet-induced non-alcoholic fatty liver disease.

    Science.gov (United States)

    Lee, Yun-Hee; Kim, Sou Hyun; Kim, Sang-Nam; Kwon, Hyun-Jung; Kim, Jeong-Dong; Oh, Ji Youn; Jung, Young-Suk

    2016-07-26

    Higher susceptibility to metabolic disease in male exemplifies the importance of sexual dimorphism in pathogenesis. We hypothesized that the higher incidence of non-alcoholic fatty liver disease in males involves sex-specific metabolic interactions between liver and adipose tissue. In the present study, we used a methionine-choline deficient (MCD) diet-induced fatty liver mouse model to investigate sex differences in the metabolic response of the liver and adipose tissue. After 2 weeks on an MCD-diet, fatty liver was induced in a sex-specific manner, affecting male mice more severely than females. The MCD-diet increased lipolytic enzymes in the gonadal white adipose tissue (gWAT) of male mice, whereas it increased expression of uncoupling protein 1 and other brown adipocyte markers in the gWAT of female mice. Moreover, gWAT from female mice demonstrated higher levels of oxygen consumption and mitochondrial content compared to gWAT from male mice. FGF21 expression was increased in liver tissue by the MCD diet, and the degree of upregulation was significantly higher in the livers of female mice. The endocrine effect of FGF21 was responsible, in part, for the sex-specific browning of gonadal white adipose tissue. Collectively, these data demonstrated that distinctively female-specific browning of white adipose tissue aids in protecting female mice against MCD diet-induced fatty liver disease.

  9. -Characterization of pyruvate kinase from the anoxia tolerant turtle, Trachemys scripta elegans: a potential role for enzyme methylation during metabolic rate depression.

    Science.gov (United States)

    Mattice, Amanda M S; MacLean, Isabelle A; Childers, Christine L; Storey, Kenneth B

    2018-01-01

    Pyruvate kinase (PK) is responsible for the final reaction in glycolysis. As PK is a glycolytic control point, the analysis of PK posttranslational modifications (PTM) and kinetic changes reveals a key piece of the reorganization of energy metabolism in an anoxia tolerant vertebrate. To explore PK regulation, the enzyme was isolated from red skeletal muscle and liver of aerobic and 20-hr anoxia-exposed red eared-slider turtles ( Trachemys scripta elegans ). Kinetic analysis and immunoblotting were used to assess enzyme function and the corresponding covalent modifications to the enzymes structure during anoxia. Both muscle and liver isoforms showed decreased affinity for phosphoenolpyruvate substrate during anoxia, and muscle PK also had a lower affinity for ADP. I 50 values for the inhibitors ATP and lactate were lower for PK from both tissues after anoxic exposure while I 50 L-alanine was only reduced in the liver. Both isozymes showed significant increases in threonine phosphorylation (by 42% in muscle and 60% in liver) and lysine methylation (by 43% in muscle and 70% in liver) during anoxia which have been linked to suppression of PK activity in other organisms. Liver PK also showed a 26% decrease in tyrosine phosphorylation under anoxia. Anoxia responsive changes in turtle muscle and liver PK coordinate with an overall reduced activity state. This reduced affinity for the forward glycolytic reaction is likely a key component of the overall metabolic rate depression that supports long term survival in anoxia tolerant turtles. The coinciding methyl- and phospho- PTM alterations present the mechanism for tissue specific enzyme modification during anoxia.

  10. Review of liver injury associated with dietary supplements.

    Science.gov (United States)

    Stickel, Felix; Kessebohm, Kerstin; Weimann, Rosemarie; Seitz, Helmut K

    2011-05-01

    Dietary supplements (DS) are easily available and increasingly used, and adverse hepatic reactions have been reported following their intake. To critically review the literature on liver injury because of DSs, delineating patterns and mechanisms of injury and to increase the awareness towards this cause of acute and chronic liver damage. Studies and case reports on liver injury specifically because of DSs published between 1990 and 2010 were searched in the PubMed and EMBASE data bases using the terms 'dietary/nutritional supplements', 'adverse hepatic reactions', 'liver injury'; 'hepatitis', 'liver failure', 'vitamin A' and 'retinoids', and reviewed for yet unidentified publications. Significant liver injury was reported after intake of Herbalife and Hydroxycut products, tea extracts from Camellia sinensis, products containing usnic acid and high contents of vitamin A, anabolic steroids and others. No uniform pattern of hepatotoxicity has been identified and severity may range from asymptomatic elevations of serum liver enzymes to hepatic failure and death. Exact estimates on how frequent adverse hepatic reactions occur as a result of DSs cannot be provided. Liver injury from DSs mimicking other liver diseases is increasingly recognized. Measures to reduce risk include tighter regulation of their production and distribution and increased awareness of users and professionals of the potential risks. © 2011 John Wiley & Sons A/S.

  11. Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes.

    Science.gov (United States)

    Wei, Hui; Wang, Erkang

    2013-07-21

    Over the past few decades, researchers have established artificial enzymes as highly stable and low-cost alternatives to natural enzymes in a wide range of applications. A variety of materials including cyclodextrins, metal complexes, porphyrins, polymers, dendrimers and biomolecules have been extensively explored to mimic the structures and functions of naturally occurring enzymes. Recently, some nanomaterials have been found to exhibit unexpected enzyme-like activities, and great advances have been made in this area due to the tremendous progress in nano-research and the unique characteristics of nanomaterials. To highlight the progress in the field of nanomaterial-based artificial enzymes (nanozymes), this review discusses various nanomaterials that have been explored to mimic different kinds of enzymes. We cover their kinetics, mechanisms and applications in numerous fields, from biosensing and immunoassays, to stem cell growth and pollutant removal. We also summarize several approaches to tune the activities of nanozymes. Finally, we make comparisons between nanozymes and other catalytic materials (other artificial enzymes, natural enzymes, organic catalysts and nanomaterial-based catalysts) and address the current challenges and future directions (302 references).

  12. Characterisation of the cytochrome P450 enzymes involved in the in vitro metabolism of granisetron.

    Science.gov (United States)

    Bloomer, J C; Baldwin, S J; Smith, G J; Ayrton, A D; Clarke, S E; Chenery, R J

    1994-01-01

    1. The metabolism of granisetron was investigated in human liver microsomes to identify the specific forms of cytochrome P450 responsible. 2. 7-hydroxy and 9'-desmethyl granisetron were identified as the major products of metabolism following incubation of granisetron with human liver microsomes. At low, clinically relevant, concentrations of granisetron the 7-hydroxy metabolite predominated. Rates of granisetron 7-hydroxylation varied over 100-fold in the human livers investigated. 3. Enzyme kinetics demonstrated the involvement of at least two enzymes contributing to the 7-hydroxylation of granisetron, one of which was a high affinity component with a Km of 4 microM. A single, low affinity, enzyme was responsible for the 9'-desmethylation of granisetron. 4. Granisetron caused no inhibition of any of the cytochrome P450 activities investigated (CYP1A2, CYP2A6, CYP2B6, CYP2C9/8, CYP2C19, CYP2D6, CYP2E1 and CYP3A), at concentrations up to 250 microM. 5. Studies using chemical inhibitors selective for individual P450 enzymes indicated the involvement of cytochrome P450 3A (CYP3A), both pathways of granisetron metabolism being very sensitive to ketoconazole inhibition. Correlation data were consistent with the role of CYP3A3/4 in granisetron 9'-desmethylation but indicated that a different enzyme was involved in the 7-hydroxylation. PMID:7888294

  13. A disposition kinetic study of Tramadol in bile duct ligated rats in perfused rat liver model.

    Science.gov (United States)

    Esmaeili, Zohre; Mohammadi, Saeid; Nezami, Alireza; Rouini, Mohammad Reza; Ardakani, Yalda Hosseinzadeh; Lavasani, Hoda; Ghazi-Khansari, Mahmoud

    2017-07-01

    Tramadol hydrochloride is a centrally acting synthetic opioid analgesic drug and is used to treat chronic pain. In this study, the effects of Bile Duct Ligation (BDL) on the pharmacokinetics of tramadol in a liver recirculating perfusion system of male rats were used. Twenty-four Wistar male rats were randomly divided into four groups: control, sham and two weeks BDL and four weeks BDL. Serum levels of liver enzymes were measured before perfusion and the pharmacokinetics of tramadol was evaluated by using liver recirculating perfusion system. Tramadol and metabolites concentrations were determined by HPLC-FL. The sharp increase in liver enzymes level in both BDL groups was observed and significant changes were also observed in liver weight and volume. Tramadol metabolites concentration significantly decreased compared with the control and sham group (Pbile duct diseases and the dose of tramadol should be accordingly adjusted. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Hypothalamic-pituitary-gonadal function in men with liver cirrhosis before and after liver transplantation

    Directory of Open Access Journals (Sweden)

    Bruno T. Zacharias

    2014-12-01

    Full Text Available Objective: To evaluate the influence of end-stage liver disease and orthotopic liver transplantation in the pituitary function and hormone metabolism before and after liver transplantation.Methods: In a prospective study, serum levels of follicle stimulating hormone (FSH, luteinizing hormone (LH, estradiol (E2 and prolactin (PRL of 30 male patients with cirrhosis were determined two to four hours before and six months after liver transplantation. The results were compared according to the Model for End-stage Liver Disease (MELD.Results: male patients with liver cirrhosis have hypogonadism. FSH was normal, but inappropriately low due to androgen failure; E2 and PRL, on their turn, were high. After liver transplantation, FSH and LH levels increased (p 18. The severity of cirrhosis had no influence on FSH, PRL and LH.

  15. Alcoholic Liver Disease and Malnutrition

    OpenAIRE

    McClain, Craig J.; Barve, Shirish S.; Barve, Ashutosh; Marsano, Luis

    2011-01-01

    Malnutrition, both protein energy malnutrition (PEM) and deficiencies in individual nutrients, is a frequent complication of alcoholic liver disease (ALD). Severity of malnutrition correlates with severity of ALD. Malnutrition also occurs in patients with cirrhosis due to etiologies other than alcohol. The mechanisms for malnutrition are multifactorial, and malnutrition frequently worsens in the hospital due to fasting for procedures and metabolic complications of liver disease, such as hepat...

  16. Lifestyle Modification through Dietary Intervention: Health Promotion of Patients with Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Manoochehr Khoshbaten

    2011-12-01

    Full Text Available Background: Prevalence of non-alcoholic fatty liver disease (NAFLD is more common worldwide and no certain treatment apart from lifestyle modification has been established yet. Available data consistently show that energy intake is significantly higher in patients with NAFLD than in individuals with no evidence of fatty liver. Changing nutritional behaviors seems to be the primary approach for treatment, simultaneously addressing all the clinical and biochemical defects. This study was aimed to examine the effects of two different composition of low energy diet (diet I vs. diet II on non-alcoholic fatty liver disease patients.Methods: In this double-blind randomized controlled trial, 44 ultrasonography-proven overweight non-alcoholic fatty liver disease patients were divided into two groups and received two low-energy diets (-500 kcal less than energy requirement individually inc. diet I (Carbohydrate: Fat: Protein: 55:25:20 and diet II (Carbohydrate: Fat: Protein: 40:40:20 for six weeks. Anthropometric and biochemical measures as well as liver enzymes were assessed after 12 hours fasting.Results: After diet I and diet II, weight decreased significantly (%1.82 and %2.45, respectively. Liver enzymes and echogenicity decreased significantly by both diet I and diet II. Mean of triglyceride concentration decreased (%18.09 after diet II (P=0.023, while there was no significant change after diet I. Significant correlations were found between changes in aspartate aminotransferase with triglyceride and LDL-C diet I.Conclusion: Low energy diets can decrease liver enzymes regardless of their composition, while diet II seems to be more effective than diet I in reduction of weight and triglyceride level.

  17. Inheritance patterns of enzymes and serum proteins of mallard-black duck hybrids

    Science.gov (United States)

    Morgan, R.P.; Meritt, D.W.; Block, S.B.; Cole, M.A.; Sulkin, S.T.; Lee, F.B.; Henny, C.J.

    1984-01-01

    From 1974 to 1976, a breeding program was used to produce hybrids of black ducks and mallards for the evaluation of inheritance patterns of serum proteins and serum, liver and muscle enzymes. In addition to the crosses designed to produce hybrids, a series of matings in 1975 and 1976 were designed to evaluate inheritance patterns of a hybrid with either a black duck or mallard. At the F1 level, hybrids were easily distinguished using serum proteins. However, once a hybrid was crossed back to either a mallard or black duck, only 12?23% of the progeny were distinguishable from black ducks or mallards using serum proteins and 23?39% using esterases. Muscle, serum and liver enzymes were similar between the two species.

  18. Effects of Delta-tocotrienol Supplementation on Liver Enzymes, Inflammation, Oxidative stress and Hepatic Steatosis in Patients with Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Pervez, Muhammad Amjad; Khan, Dishad Ahmet; Ijaz, Aamir; Khan, Shamrez

    2018-03-01

    Non-alcoholic fatty liver disease (NAFLD) is a growing public health problem worldwide and is associated with increased morbidity and mortality. Currently, there is no definitive treatment for this disease. δ-Tocotrienol has potent anti-inflammatory and antioxidant properties and may reduce liver injury in NAFLD. The present study aims to evaluate the efficacy and safety of δ-tocotrienol in the treatment of NAFLD. The present study was a randomized, double-blind, placebo-controlled pilot study conducted in patients aged > 20 years, belonging to both sexes, having ultrasound-proven fatty liver disease, having a fatty liver index (FLI) of ≥ 60, and persistent elevation of alanine transaminase. A total of 71 patients were assigned to receive either oral δ-tocotrienol (n=35, 300 mg twice daily) or placebo (n=36) for 12 weeks. At the baseline and at the end of the study, clinical and biochemical parameters, including lipid profile, liver function tests, high-sensitivity C-reactive protein (hs-CRP), and malondialdehyde (MDA) were measured. Body mass index and FLI were calculated, and ultrasound grading of hepatic steatosis was performed. Out of 71 enrolled patients, 64 patients, 31 in the δ-tocotrienol group and 33 in the placebo group, completed the study. After 12 weeks of supplementation, δ-tocotrienol showed greater efficacy than placebo by decreasing serum aminotransferases, hs-CRP, MDA, and FLI score (phepatic steatosis on ultrasound examination. No adverse effects were reported. δ-Tocotrienol was safe, and it effectively improved aminotransferase levels and inflammatory and oxidative stress markers in patients with NAFLD. Large-scale randomized clinical trials are warranted to further support these findings.

  19. PULMONARY AND LIVER DAMAGE DURING TREATMENT WITH ACETAMINOPHEN (PARACETAMOL

    Directory of Open Access Journals (Sweden)

    L. I. Dvoretski

    2016-01-01

    Full Text Available This is a case report of pulmonary damage in the form of intestinal pneumonitis with severe respiratory failure during administration of acetaminophen (paracetamol. In addition, significant increase of ALT and AST levels without clinical signs of liver damage was observed in this patient. After glucocorticoids administration regression of radiological abnormal findings in the lungs along with normalization of liver enzymes values were registered. The rarity of interstitial pneumonitis induced by acetaminophen (paracetamol, especially in combination with liver damage, is emphasized. The presented patient history is the first case report of drug-induced hepatopulmonary syndrome during acetaminophen (paracetamol administration.

  20. Purification and characterization of rat liver minoxidil sulphotransferase.

    Science.gov (United States)

    Hirshey, S J; Falany, C N

    1990-01-01

    Minoxidil (Mx), a pyrimidine N-oxide, is used therapeutically as an antihypertensive agent and to induce hair growth in patients with male pattern baldness. Mx NO-sulphate has been implicated as the agent active in producing these effects. This paper describes the purification of a unique sulphotransferase (ST) from rat liver cytosol that is capable of catalysing the sulphation of Mx. By using DEAE-Sepharose CL-6B chromatography, hydroxyapatite chromatography and ATP-agarose affinity chromatography, Mx-ST activity was purified 240-fold compared with the activity in cytosol. The purified enzyme was also capable of sulphating p-nitrophenol (PNP) at low concentrations (less than 10 microM). Mx-ST was purified to homogeneity, as evaluated by SDS/PAGE and reverse-phase h.p.l.c. The active form of the enzyme had a molecular mass of 66,000-68,000 Da as estimated by gel exclusion chromatography and a subunit molecular mass of 35,000 Da. The apparent Km values for Mx, 3'-phosphoadenosine 5'-phosphosulphate and PNP were 625 microM, 5.0 microM and 0.5 microM respectively. However, PNP displayed potent substrate inhibition at concentrations above 1.2 microM. Antibodies raised in rabbits to the pure enzyme detected a single band in rat liver cytosol with a subunit molecular mass of 35,000 Da, as determined by immunoblotting. The anti-(rat Mx-ST) antibodies also reacted with the phenol-sulphating form of human liver phenol sulphotransferase, suggesting some structural similarity between these proteins. Images Fig. 5. Fig. 6. Fig. 7. PMID:2241904

  1. Effect of airplane transport of donor livers on post-liver transplantation survival.

    Science.gov (United States)

    Huang, Yi; MacQuillan, Gerry; Adams, Leon A; Garas, George; Collins, Megan; Nwaba, Albert; Mou, Linjun; Bulsara, Max K; Delriviere, Luc; Jeffrey, Gary P

    2016-11-07

    To evaluate the effect of long haul airplane transport of donor livers on post-transplant outcomes. A retrospective cohort study of patients who received a liver transplantation was performed in Perth, Australia from 1992 to 2012. Donor and recipient characteristics information were extracted from Western Australian liver transplantation service database. Patients were followed up for a mean of six years. Patient and graft survival were evaluated and compared between patients who received a local donor liver and those who received an airplane transported donor liver. Predictors of survival were determined by univariate and multivariate analysis using cox regression. One hundred and ninety-three patients received a local donor liver and 93 patients received an airplane transported donor liver. Airplane transported livers had a significantly lower alanine transaminase (mean: 45 U/L vs 84 U/L, P = 0.035), higher donor risk index (mean: 1.88 vs 1.42, P airplane transport retained significance for graft loss (HR = 1.92, 95%CI: 1.16-3.17). One year graft survival was 0.88 for those with a local liver and was 0.71 for those with an airplane transported liver. One year graft loss was due to primary graft non-function or associated with preservation injury in 20.8% of recipients of an airplane transported liver compared with 4.6% in those with a local liver ( P = 0.027). Airplane transport of donor livers was independently associated with reduced graft survival following liver transplantation.

  2. The levels of liver enzymes and atypical lymphocytes are higher in youth patients with infectious mononucleosis than in preschool children.

    Science.gov (United States)

    Wang, Yan; Li, Jun; Ren, Yuan-Yuan; Zhao, Hong

    2013-12-01

    Infectious mononucleosis (IM) is the clinical presentation of primary infection with Epstein-Barr virus. Although the literature contains a massive amount of information on IM, most of this is related specifically to only children or adults separately. In order to distinguish any differences between preschool children and youth patients, we retrospectively analyzed their demographic and clinical features. Records of patients hospitalized from December 2001 to September 2011 with a diagnosis of IM were retrieved from Peking University First Hospital, which is a tertiary teaching hospital in Beijing. The demographic data and clinical characteristics were collected. IM was diagnosed in 287 patients during this 10-year period, with incidence peaks among preschool children (≤7 years old, 130/287, 45.3%) and youth patients (>15 and <24 years old, 101/287, 35.2%). Although the complaints at admission did not differ between these two patient groups, the incidence of clinical signs (tonsillopharyngitis, lymphadenopathy, hepatomegaly, and edema of the eyelids) was much higher in preschool children. The incidence of liver lesion and percentage of atypical lymphocytes were significantly higher in the youth group (P<0.001), and the average hospital stay was longer in this group. Pneumonia was the most common complication, and there was no case of mortality. The incidence of IM peaks among preschool children and youth patients in Beijing, China. The levels of liver enzymes and atypical lymphocytes increase with age.

  3. The levels of liver enzymes and atypical lymphocytes are higher in youth patients with infectious mononucleosis than in preschool children

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2013-12-01

    Full Text Available Background/AimsInfectious mononucleosis (IM is the clinical presentation of primary infection with Epstein-Barr virus. Although the literature contains a massive amount of information on IM, most of this is related specifically to only children or adults separately. In order to distinguish any differences between preschool children and youth patients, we retrospectively analyzed their demographic and clinical features.MethodsRecords of patients hospitalized from December 2001 to September 2011 with a diagnosis of IM were retrieved from Peking University First Hospital, which is a tertiary teaching hospital in Beijing. The demographic data and clinical characteristics were collected.ResultsIM was diagnosed in 287 patients during this 10-year period, with incidence peaks among preschool children (≤7 years old, 130/287, 45.3% and youth patients (>15 and <24 years old, 101/287, 35.2%. Although the complaints at admission did not differ between these two patient groups, the incidence of clinical signs (tonsillopharyngitis, lymphadenopathy, hepatomegaly, and edema of the eyelids was much higher in preschool children. The incidence of liver lesion and percentage of atypical lymphocytes were significantly higher in the youth group (P<0.001, and the average hospital stay was longer in this group. Pneumonia was the most common complication, and there was no case of mortality.ConclusionsThe incidence of IM peaks among preschool children and youth patients in Beijing, China. The levels of liver enzymes and atypical lymphocytes increase with age.

  4. Characterisation of the cytochrome P450 enzymes involved in the in vitro metabolism of granisetron.

    OpenAIRE

    Bloomer, J C; Baldwin, S J; Smith, G J; Ayrton, A D; Clarke, S E; Chenery, R J

    1994-01-01

    1. The metabolism of granisetron was investigated in human liver microsomes to identify the specific forms of cytochrome P450 responsible. 2. 7-hydroxy and 9'-desmethyl granisetron were identified as the major products of metabolism following incubation of granisetron with human liver microsomes. At low, clinically relevant, concentrations of granisetron the 7-hydroxy metabolite predominated. Rates of granisetron 7-hydroxylation varied over 100-fold in the human livers investigated. 3. Enzyme...

  5. Nonalcoholic fatty liver disease: Update on pathogenesis, diagnosis, treatment and the role of S-adenosylmethionine

    Science.gov (United States)

    Mato, José M; Lu, Shelly C

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is currently the most common liver disease worldwide affecting over one-third of the population in the U.S. It has been associated with obesity, type 2 diabetes, hyperlipidemia, and insulin resistance and is initiated by the accumulation of triglycerides in hepatocytes. Isolated hepatic steatosis (IHS) remains a benign process, while a subset develops superimposed inflammatory activity and progression to nonalcoholic steatohepatitis (NASH) with or without fibrosis. However, the molecular mechanisms underlying NAFLD progression are not completely understood. Liver biopsy is still required to differentiate IHS from NASH as easily accessible noninvasive biomarkers are lacking. In terms of treatments for NASH, pioglitazone, vitamin E, and obeticholic acid have shown some benefit. All of these agents have potential complications associated with long-term use. Nowadays, a complex hypothesis suggests that multiple parallel hits are involved in NASH development. However, the ‘key switch’ between IHS and NASH remains to be discovered. We have recently shown that knocking out enzymes involved in S-adenosylmethionine (SAMe) metabolism, the main biological methyl donor in humans that is abundant in the liver, will lead to NASH development in mice. This could be due to the fact that a normal SAMe level is required to establish the proper ratio of phosphatidylethanolamine to phosphatidylcholine that has been found to be important in NAFLD progression. New data from humans have also suggested that these enzymes play a role in the pathogenesis of NAFLD and that some of SAMe cycle metabolites may serve as noninvasive biomarkers of NASH. In this review, we discuss the evidence of the role of SAMe in animal models and humans with NAFLD and how studying this area may lead to the discovery of new noninvasive biomarkers and possibly personalized treatment for NASH. PMID:25873078

  6. Heme synthesis in normal mouse liver and mouse liver tumors

    International Nuclear Information System (INIS)

    Stout, D.L.; Becker, F.F.

    1990-01-01

    Hepatic cancers from mice and rats demonstrate decreased levels of delta-aminolevulinic acid synthase, the rate-limiting enzyme in the heme synthetic pathway, and increased heme oxygenase, the heme-catabolizing enzyme. These findings suggest that diminution of P-450, b5, and catalase in these lesions may result from a heme supply that is limited by decreased heme synthesis and increased heme catabolism. Heme synthesis was measured in mouse liver tumors (MLT) and adjacent tumor-free lobes (BKG) by administering the radiolabeled heme precursors 55 FeCl3 and [2- 14 C]glycine and subsequently extracting the heme for determination of specific activity. Despite reduced delta-aminolevulinic acid synthase activity in MLT, both tissues incorporated [2-14C]glycine into heme at similar rates. At early time points, heme extracted from MLT contained less 55Fe than that from BKG. This was attributed to the findings that MLT took up 55Fe at a slower rate than BKG and had larger iron stores than BKG. The amount of heme per milligram of protein was also similar in both tissues. These findings militate against the hypothesis that diminished hemoprotein levels in MLT result from limited availability of heme. It is probable, therefore, that decreased hemoprotein levels in hepatic tumors are linked to a general program of dedifferentiation associated with the cancer phenotype. Diminution of hemoprotein in MLT may result in a relatively increased intracellular heme pool. delta-Aminolevulinic acid synthase and heme oxygenase are, respectively, negatively and positively regulated by heme. Thus, their alteration in MLT may be due to the regulatory influences of the heme pool

  7. Threonine phosphorylation of rat liver glycogen synthase

    International Nuclear Information System (INIS)

    Arino, J.; Arro, M.; Guinovart, J.J.

    1985-01-01

    32 P-labeled glycogen synthase specifically immunoprecipitated from 32 P-phosphate incubated rat hepatocytes contains, in addition to [ 32 P] phosphoserine, significant levels of [ 32 P] phosphothreonine. When the 32 P-immunoprecipitate was cleaved with CNBr, the [ 32 P] phosphothreonine was recovered in the large CNBr fragment (CB-2, Mapp 28 Kd). Homogeneous rat liver glycogen synthase was phosphorylated by all the protein kinases able to phosphorylate CB-2 in vitro. After analysis of the immunoprecipitated enzyme for phosphoaminoacids, it was observed that only casein kinase II was able to phosphorylate on threonine and 32 P-phosphate was only found in CB-2. These results demonstrate that rat liver glycogen synthase is phosphorylated at threonine site(s) contained in CB-2 and strongly indicate that casein kinase II may play a role in the ''in vivo'' phosphorylation of liver glycogen synthase. This is the first protein kinase reported to phosphorylate threonine residues in liver glycogen synthase

  8. Extended interval between enzyme therapy infusions for adult patients with Gaucher′s disease type 1.

    Directory of Open Access Journals (Sweden)

    Pérez-Calvo J

    2003-01-01

    Full Text Available BACKGROUND: Enzyme replacement therapy (ERT for Gaucher′s disease with alglucerase or imiglucerase is efficacious, well-tolerated and safe. However, cost considerations, visits to medical facilities, potentially duration of theray for life, are issues of major concern to a proportion of treated patients and has, in some cases, led to the withdrawal of therapy. AIMS: To elucidate whether an extension of the interval between enzyme infusions to once every three weeks is as effective in maintaining the clinical responses achieved with the bi-monthly regimen. MATERIALS AND METHODS: Four patients with an optimal response to ERT (at 30 units/kg every two weeks for an average of 27 months, were subjected to enzyme dose/frequency changes that essentially constituted a reduction in cumulative dose over the treatment period. Patients were assessed every 6 months for alterations in haematological parameters, plasma chitotriosidase levels, liver and spleen size, and bone symptoms. RESULTS: All patients had to resume the previous infusion schedule of once every two weeks; one because of new bone marrow infiltrates, two because of visceral enlargement, and the fourth due to progressive anaemia. CONCLUSIONS: This limited experience suggests that a reduction in enzyme dose associated with an extended interval between infusions may lead to variable disease control, and underscores the need for individualization of enzyme therapy.

  9. Protective Effect of Free and Bound Polyphenol Extracts from Ginger (Zingiber officinale Roscoe on the Hepatic Antioxidant and Some Carbohydrate Metabolizing Enzymes of Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Mutiu Idowu Kazeem

    2013-01-01

    Full Text Available This study investigated the hepatoprotective effects of polyphenols from Zingiber officinale on streptozotocin-induced diabetic rats by assessing liver antioxidant enzymes, carbohydrate-metabolizing enzymes and liver function indices. Initial oral glucose tolerance test was conducted using 125 mg/kg, 250 mg/kg, and 500 mg/kg body weight of both free and bound polyphenols from Z. officinale. 28 day daily oral administration of 500 mg/kg body weight of free and bound polyphenols from Z. officinale to streptozotocin-induced (50 mg/kg diabetic rats significantly reduced (P<0.05 the fasting blood glucose compared to control groups. There was significant increase (P<0.05 in the antioxidant enzymes activities in the animals treated with both polyphenols. Similarly, the polyphenols normalised the activities of some carbohydrate metabolic enzymes (hexokinase and phosphofructokinase in the liver of the rats treated with it and significantly reduced (P<0.05 the activities of liver function enzymes. The results from the present study have shown that both free and bound polyphenols from Z. officinale especially the free polyphenol could ameliorate liver disorders caused by diabetes mellitus in rats. This further validates the use of this species as medicinal herb and spice by the larger population of Nigerians.

  10. Increased carboxyhemoglobin level during liver resection with inflow occlusion.

    Science.gov (United States)

    Godai, Kohei; Hasegawa-Moriyama, Maiko; Kuniyoshi, Tamotsu; Matsunaga, Akira; Kanmura, Yuichi

    2013-04-01

    Controlling stress responses associated with ischemic changes due to bleeding and ischemia/reperfusion injury is essential for anesthetic management. Endogenous carboxyhemoglobin (COHb) is produced in the oxidative degradation of heme proteins by the stress-response enzyme heme oxygenase. Although the COHb level is elevated in critically ill patients, changes in endogenous COHb during anesthesia have not been well investigated. Therefore, we evaluated changes in endogenous COHb levels in patients undergoing liver resections with inflow occlusion. Levels of COHb were significantly increased after the Pringle maneuver. The inflow occlusion time in patients with increased COHb after the Pringle maneuver (∆COHb > 0.3 %) was significantly longer than in patients without increased COHb (∆COHb < 0.3 %) (P = 0.01). In addition, COHb changes were correlated with inflow occlusion time (P = 0.005, R(2) = 0.21). Neither total blood loss, transfusion volume of packed red blood cells, operation time, nor anesthetic time differed between patients with and without increased COHb. The results indicated that endogenous COHb levels were increased by inflow occlusion in patients undergoing liver resections, which suggests that changes in COHb may correlate with hepatic ischemia/reperfusion injury induced by inflow occlusion.

  11. A three-dimensional in vitro HepG2 cells liver spheroid model for genotoxicity studies.

    Science.gov (United States)

    Shah, Ume-Kulsoom; Mallia, Jefferson de Oliveira; Singh, Neenu; Chapman, Katherine E; Doak, Shareen H; Jenkins, Gareth J S

    2018-01-01

    The liver's role in metabolism of chemicals makes it an appropriate tissue for toxicity testing. Current testing protocols, such as animal testing and two-dimensional liver cell systems, offer limited resemblance to in vivo liver cell behaviour, in terms of gene expression profiles and metabolic competence; thus, they do not always accurately predict human toxicology. In vitro three-dimensional liver cell models offer an attractive alternative. This study reports on the development of a 3D liver model, using HepG2 cells, by a hanging-drop technique, with a focus on evaluating spheroid growth characteristics and suitability for genotoxicity testing. The cytokinesis-blocked micronucleus assay protocol was adapted to enable micronucleus (MN) detection in the 3D spheroid models. This involved evaluating the difference between hanging vs non-hanging drop positions for dosing of the test agents and comparison of automated Metafer scoring with manual scoring for MN detection in HepG2 spheroids. The initial seeding density, used for all experiments, was 5000 cells/20 μl drop hanging spheroids, harvested on day 4, with >75% cell viability. Albumin secretion (7.8 g/l) and both CYP1A1 and CYP1A2 gene expression were highest in the 3D environment at day 4. Exposure to metabolically activated genotoxicants for 24 h resulted in a 6-fold increase in CYP1A1 enzyme activity (3 μM B[a]P) and a 30-fold increase in CYP1A2 enzyme activity (5 μM PhIP) in 3D hanging spheroids. MN inductions in response to B[a]P or PhIP were 2-fold and 3-fold, respectively, and were greater in 3D hanging spheroids than in 2D format, showing that hanging spheroids are more sensitive to genotoxic agents. HepG2 hanging-drop spheroids are an exciting new alternative system for genotoxicity studies, due to their improved structural and physiological properties, relative to 2D cultures. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Angiotensin converting enzyme (ACE D/I) polymorphism and its ...

    African Journals Online (AJOL)

    Hepatitis C virus (HCV) infection is a global health problem in Egypt and causes different liver disease spectrum. Evidence indicates that angiotensin I converting enzyme (ACE) gene polymorphism may play a role in determining disease progression. We aimed to determine the association of ACE gene I/D polymorphism ...

  13. Growth hormone increases and maturation decreases glutamine synthetase turnover rate in rat liver

    International Nuclear Information System (INIS)

    Lin, C.K.

    1985-01-01

    An investigation was made of the effect of hypophysectomy and growth hormone (GH) replacement regimen (1 mg/100 g twice daily for 30 days); and maturation (from 25 up to 90 days) on the liver and brain glutamine synthetase (GS) mass and turnover rates in rats. The first order decay rate of enzyme 14 C radioactivity was determined between 1 and 4 days to obtain the half-life (T/sub 1/2/) of GS. The hepatic GS mass was determined by immunoassay. GS turnover (GS/sub s/) was calculated from T/sub 1/2/ and the GS mass (i.e., K = 0.693/T/sub 1/2/; GS/sub s/ = K x GS mass). It was concluded that: (1) GS specific activity is not decreased by hypophysectomy or increased by GH. These results suggested that observed endocrine induced changes in GS are due to changes in GS mass. (2) The liver GS turnover rate is significantly reduced by hypophysectomy and increased by GH replacement. It was proposed that GH specifically enhances synthesis of GS in the liver. (3) Maturation (25, 40, 60, and 90 days) decreases GS turnover rate in both liver and brain of normal rats. This similar effect of maturation suggests that the observed age induced decline in GS turnover rate is not related to GH in all tissues

  14. Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, P

    1983-01-01

    in patients with alcoholic cirrhosis. This decrease seems to be due to decreased liver function, decreasing hepatic blood flow, and increased portosystemic shunting. Oral testosterone loading may therefore be of prognostic significance in patients with alcoholic liver cirrhosis.......The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.......8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely...

  15. Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

    Science.gov (United States)

    Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

    2018-02-09

    Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

  16. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial.

    Science.gov (United States)

    Loguercio, Carmela; Andreone, Pietro; Brisc, Ciprian; Brisc, Michaela Cristina; Bugianesi, Elisabetta; Chiaramonte, Maria; Cursaro, Carmela; Danila, Mirela; de Sio, Ilario; Floreani, Annarosa; Freni, Maria Antonietta; Grieco, Antonio; Groppo, Marzia; Lazzari, Roberta; Lobello, Salvatore; Lorefice, Elisabetta; Margotti, Marzia; Miele, Luca; Milani, Stefano; Okolicsanyi, Lajos; Palasciano, Giuseppe; Portincasa, Piero; Saltarelli, Patrizia; Smedile, Antonina; Somalvico, Francesco; Spadaro, Aldo; Sporea, Ioan; Sorrentino, Paolo; Vecchione, Raffaela; Tuccillo, Concetta; Del Vecchio Blanco, Camillo; Federico, Alessandro

    2012-05-01

    The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Chimeric mice with humanized liver: Application in drug metabolism and pharmacokinetics studies for drug discovery.

    Science.gov (United States)

    Naritomi, Yoichi; Sanoh, Seigo; Ohta, Shigeru

    2018-02-01

    Predicting human drug metabolism and pharmacokinetics (PK) is key to drug discovery. In particular, it is important to predict human PK, metabolite profiles and drug-drug interactions (DDIs). Various methods have been used for such predictions, including in vitro metabolic studies using human biological samples, such as hepatic microsomes and hepatocytes, and in vivo studies using experimental animals. However, prediction studies using these methods are often inconclusive due to discrepancies between in vitro and in vivo results, and interspecies differences in drug metabolism. Further, the prediction methods have changed from qualitative to quantitative to solve these issues. Chimeric mice with humanized liver have been developed, in which mouse liver cells are mostly replaced with human hepatocytes. Since human drug metabolizing enzymes are expressed in the liver of these mice, they are regarded as suitable models for mimicking the drug metabolism and PK observed in humans; therefore, these mice are useful for predicting human drug metabolism and PK. In this review, we discuss the current state, issues, and future directions of predicting human drug metabolism and PK using chimeric mice with humanized liver in drug discovery. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  18. Two enzymes catalyze vitamin K 2,3-epoxide reductase activity in mouse: VKORC1 is highly expressed in exocrine tissues while VKORC1L1 is highly expressed in brain.

    Science.gov (United States)

    Caspers, Michael; Czogalla, Katrin J; Liphardt, Kerstin; Müller, Jens; Westhofen, Philipp; Watzka, Matthias; Oldenburg, Johannes

    2015-05-01

    VKORC1 and VKORC1L1 are enzymes that both catalyze the reduction of vitamin K2,3-epoxide via vitamin K quinone to vitamin K hydroquinone. VKORC1 is the key enzyme of the classical vitamin K cycle by which vitamin K-dependent (VKD) proteins are γ-carboxylated by the hepatic γ-glutamyl carboxylase (GGCX). In contrast, the VKORC1 paralog enzyme, VKORC1L1, is chiefly responsible for antioxidative function by reduction of vitamin K to prevent damage by intracellular reactive oxygen species. To investigate tissue-specific vitamin K 2,3-epoxide reductase (VKOR) function of both enzymes, we quantified mRNA levels for VKORC1, VKORC1L1, GGCX, and NQO1 and measured VKOR enzymatic activities in 29 different mouse tissues. VKORC1 and GGCX are highly expressed in liver, lung and exocrine tissues including mammary gland, salivary gland and prostate suggesting important extrahepatic roles for the vitamin K cycle. Interestingly, VKORC1L1 showed highest transcription levels in brain. Due to the absence of detectable NQO1 transcription in liver, we assume this enzyme has no bypass function with respect to activation of VKD coagulation proteins. Our data strongly suggest diverse functions for the vitamin K cycle in extrahepatic biological pathways. Copyright © 2015. Published by Elsevier Ltd.

  19. Isolation and purification of rat liver morphine UDP-glucuronosyltransferase

    International Nuclear Information System (INIS)

    Puig, J.F.; Tephly, T.R.

    1986-01-01

    The enhancement of rat liver microsomal morphine (M) and 4-hydroxybiphenyl (4-HBP) UDP-glucuronyltransferase (UDPGT) activities by phenobarbital treatment has been proposed to represent increased activity of a single enzyme form, GT-2. They have separated M and 4-HBP UDPGT activities from Emulgen 911-solubilized microsomes obtained from livers of phenobarbital-treated Wistar rats. A sensitive assay procedure was developed to quantify M-UDPGT and 4-HBP-UDPGT activities using 14 C-UDP-glucuronic acid (UDPGA) and reversed phase C-18 minicolumns whereby the radioactive glucuronides were differentially eluted from labeled UDPGA. Trisacryl DEAE, and chromatofocusing procedures were employed to separate M-UDPGT and 4-HBP-UDPGT in the presence of exogenous phosphatidylcholine (PC). The PC is necessary to stabilize UDPGT activities. M-UDPGT was isolated to apparent homogeneity and displayed a monomeric molecular weight of 56,000 daltons on SDS-PAGE. It reacted with M but not with 4-HBP, bilirubin, p-nitrophenol, testosterone, androsterone, estrone, 4-aminobiphenyl or α-naphthylamine. 4-HBP-UDPGT did not react with M. Therefore, M and 4-HBP glucuronidations are catalyzed by separate enzymes in rat liver microsomes

  20. Effect of high dietary copper on growth, antioxidant and lipid metabolism enzymes of juvenile larger yellow croaker Larimichthys croceus

    Directory of Open Access Journals (Sweden)

    Fanxing Meng

    2016-05-01

    Full Text Available A study was carried out to test the responses of juvenile larger yellow croaker Larimichthys croceus to high Cu intake. Experimental diets were formulated containing three levels of Cu: low Cu (3.67 mg/kg, middle Cu (13.65 mg/kg and high Cu (25.78 mg/kg, and each diet were fed to large yellow croaker in triplicate for 10 weeks. Final body weight, weight gain and feed intake were the lowest in high Cu group, but hepatosomatic index was the highest; Cu concentrations in the whole-body, muscle and liver of fish fed low Cu diet was the lowest; Liver superoxide dismutase, catalase and glutathione peroxidase activities in fish fed high Cu diet were lower than those in fish fed other diets; The higher content of liver thiobarbituric acid reactive substance content was found in high Cu group, followed by middle Cu group, and the lowest in low Cu group; Liver 6-phosphogluconate dehydrogenase, glucose-6-phosphate dehydrogenase, malic enzyme, isocitrate dehydrogenase and fatty acid synthase activities were the lowest in high Cu group, but lipoprotein lipase activity was the highest. This study indicated that high copper intake reduced growth of juvenile larger yellow croaker, inhibited activities of antioxidant enzymes and lipid synthetases, and led to energy mobilization. Keywords: Larger yellow croaker, Copper, Antioxidant enzyme, Lipid metabolism enzyme

  1. Mathematical modeling of liver metastases tumour growth and control with radiotherapy

    International Nuclear Information System (INIS)

    Campbell, Adrienne; Sivakumaran, Thiru; Wong, Eugene; Davidson, Melanie; Lock, Michael

    2008-01-01

    Generating an optimized radiation treatment plan requires understanding the factors affecting tumour control. Mathematical models of tumour dynamics may help in future studies of factors predicting tumour sensitivity to radiotherapy. In this study, a time-dependent differential model, incorporating biological cancer markers, is presented to describe pre-treatment tumour growth, response to radiation, and recurrence. The model uses Gompertzian-Exponential growth to model pre-treatment tumour growth. The effect of radiotherapy is handled by a realistic cell-kill term that includes a volume-dependent change in tumour sensitivity. Post-treatment, a Gompertzian, accelerated, delayed repopulation is employed. As proof of concept, we examined the fit of the model's prediction using various liver enzyme levels as markers of metastatic liver tumour growth in a liver cancer patient. A tumour clonogen population model was formulated. Each enzyme was coupled to the same tumour population, and served as surrogates of the tumour. This dynamical model was solved numerically and compared to the measured enzyme levels. By minimizing the mean-squared error of the model enzyme predictions, we determined the following tumour model parameters: growth rate prior to treatment was 0.52% per day; the fractional radiation cell kill for the prescribed dose (60 Gy in 15 fractions) was 42% per day, and the tumour repopulation rate was 2.9% per day. These preliminary results provided the basis to test the model in a larger series of patients, to apply biological markers for improving the efficacy of radiotherapy by determining the underlying tumour dynamics.

  2. Histochemical study of the distribution of a few enzymes in the digestive system of Indian parrot.

    Science.gov (United States)

    Mohan, K; Agrawal, V P; Goel, K A

    1977-01-01

    Acid-and alkaline phosphatase, 5-nucleotidase and lipase have been localized histochemically in the gizzard, intestine liver and pancreas of Indian parrot, Psittacula krameri. In the gizzard and intestine, the mucosal epithelial cells are the main sites for the enzyme production. The tubular glands of the gizzard show intense reaction for all the enzymes tested. The hepatic sinusoid cells of the liver and the acinii of pancreas give positive reaction. Like pancreas, the intestine has also been found responsible for the production and secretion of lipase. Functional significance of phosphatases in the tissues tested has been discussed.

  3. Enzyme hydration, activity and flexibility : A neutron scattering approach

    International Nuclear Information System (INIS)

    Kurkal-Siebert, V.; Finney, J.L.; Daniel, R.M.; Smith, Jeremy C.

    2006-01-01

    Recent measurements have demonstrated enzyme activity at hydrations as low as 3%. The question of whether the hydration-induced enzyme flexibility is important for activity is addressed by performing picosecond dynamic neutron scattering experiments on pig liver esterase powders at various temperatures as well as solutions. At all temperatures and hydrations investigated here, significant quasielastic scattering intensity is found in the protein, indicating the presence of anharmonic, diffusive motion. As the hydration increases a temperature-dependent dynamical transition appears and strengthens involving additional diffusive motion. At low temperature, increasing hydration resulted in lower flexibility of the enzyme. At higher temperatures, systems containing sufficient number of water molecules interacting with the protein exhibit increased flexibility. The implication of these results is that, although the additional hydration-induced diffusive motion and flexibility at high temperatures in the enzyme detected here may be related to increased activity, they are not required for the enzyme to function

  4. Hepatoprotective effects of setarud against carbon tetrachloride-induced liver injury in rats.

    Science.gov (United States)

    Khorshid, Hamid Reza Khorram; Azonov, Jahan A; Novitsky, Yury A; Farzamfar, Bardia; Shahhosseiny, Mohammad Hassan

    2008-01-01

    To assess the hepatoprotective activity of a new herbal drug "setarud" in experimental liver fibrosis, 48 male Wistar rats were divided into four groups: controls, carbon tetrachloride (CCl4) group, and two treatment groups that received CCl4 and setarud at doses of 0.02 or 0.04 g/Kg/day for 30 days. Body weight gain, biochemical liver tests, bile flow rate and composition, and changes in liver morphology in the four groups were studied. CCl4 administration led to morphological and biochemical evidence of liver injury as compared to untreated controls. Setarud administration led to significant protection against CCl4-induced changes in body weight gain, liver morphology, bile flow and concentration. It was also associated with significantly lower serum liver enzyme levels (pliver disease are warranted.

  5. [A case of liver abscess due to Streptococcus anginosus infection secondary to a dental extraction].

    Science.gov (United States)

    Iwashita, Hideyuki; Matsui, Noriaki; Tsukamoto, Shinji; Funakoshi, Sadahiro; Yamaguchi, Masashi; Kabemura, Teppei; Sohda, Tetsuro; Sakisaka, Shotaro

    2015-08-01

    A 74-year-old man was referred to our hospital because of a high fever. He had undergone a dental extraction about 1 month prior to admission because of apical periodontitis. Imaging study revealed liver abscess lesions. Infection with Streptococcus anginosus was confirmed using both stab and blood culture. An adequate selection of antibiotics was administered, and a good outcome was obtained. There have been no case reports of liver abscess caused by intraoral commensal flora related to dental extraction in healthy adults. This case shows that liver abscesses can occur secondary to dental extractions, even in healthy adults.

  6. Struktuur en interaktie analyse van NAD+ en NAD+ analoga in horse liver alcohol dehydrogenase

    NARCIS (Netherlands)

    Beijer, N.A.

    1988-01-01

    Dit verslag beschrijft een studie naar de relatie tussen struktuur en funktie voor het co-enzym NAn+ en zijn analoga in de aktieve holte van het enzym Horse Liver Alcohol Dehydrogenase (LADH). De rol van NAD+ in enzymgekatalyseerde oxidatie-reduktie reakties is die van het bewerkstelligen van een

  7. Safety and Yield of Diagnostic ERCP in Liver Transplant Patients with Abnormal Liver Function Tests

    Directory of Open Access Journals (Sweden)

    Jayapal Ramesh

    2014-01-01

    Full Text Available Background. Abnormal liver enzymes postorthotopic liver transplant (OLT may indicate significant biliary pathology or organ rejection. There is very little known in the literature regarding the current role of diagnostic ERCP in this scenario. Aim. To review the utility of diagnostic ERCP in patients presenting with abnormal liver function tests in the setting of OLT. Methods. A retrospective review of diagnostic ERCPs in patients with OLT from 2002 to 2013 from a prospectively maintained, IRB approved database. Results. Of the 474 ERCPs performed in OLT patients, 210 (44.3%; 95% CI 39.8–48.8 were performed for abnormal liver function tests during the study period. Majority of patients were Caucasian (83.8%, male (62.4% with median age of 55 years (IQR 48–62 years. Biliary cannulation was successful in 99.6% of cases and findings included stricture in 45 (21.4 %; biliary stones/sludge in 23 (11%; biliary dilation alone in 31 (14.8%; and normal in 91 (43.3%. Three (1.4% patients developed mild, self-limiting pancreatitis; one patient (0.5% developed cholangitis and two (1% had postsphincterotomy bleeding. Multivariate analyses showed significant association between dilated ducts on imaging with a therapeutic outcome. Conclusion. Diagnostic ERCP in OLT patients presenting with liver function test abnormalities is safe and frequently therapeutic.

  8. Aminotransferaza asparaginianowa – kluczowy enzym w metabolizmie ogólnoustrojowym człowieka

    Directory of Open Access Journals (Sweden)

    Dagmara Otto-Ślusarczyk

    2016-03-01

    Full Text Available Aspartate aminotransferase is an organ - nonspecific enzyme located in many tissues of the human body where it catalyzes reversible reaction of transamination. There are two aspartate aminotransferase isoforms - cytoplasmic (AST1 and mitochondrial (AST2, that usually occur together and interact with each other metabolically. Both isoforms are homodimers containing highly conservative regions responsible for catalytic properties of enzyme. The common feature of all aspartate aminotransfeses is Lys – 259 residue covalent binding with prosthetic group - pyridoxal phosphate. The differences in the primary structure of AST isoforms determine their physico-chemical, kinetic and immunological properties. Because of the low concentration of L-aspartate (L-Asp in the blood, AST is the only enzyme, which supply of this amino acid as a substrate for many metabolic processes, such as urea cycle or purine and pyrimidine nucleotides in the liver, synthesis of L-arginine in the kidney and purine nucleotide cycle in the brain and the skeletal muscle. AST is also involved in D-aspartate production that regulates the metabolic activity at the auto-, para- and endocrine level. Aspartate aminotransferase is a part of the malate-aspartate shuttle in the myocardium, is involved in gluconeogenesis in the liver and kidney, glyceroneogenesis in the adipose tissue, and synthesis of neurotransmitters and neuro-glial pathway in the brain. Recently, the significant role of AST in glutaminolysis - normal metabolic pathway in tumor cells, was demonstrated. The article is devoted the role of AST, known primarily as a diagnostic liver enzyme, in metabolism of various human tissues and organs.

  9. Tocilizumab-Induced Acute Liver Injury in Adult Onset Still’s Disease

    Directory of Open Access Journals (Sweden)

    Michael Drepper

    2013-01-01

    Full Text Available Background. Tocilizumab, a monoclonal humanized anti-IL-6 receptor antibody, is used in treatment of refractory adult onset Still’s disease (AOSD. Mild to moderate liver enzyme elevation is a well-known side effect, but severe liver injury has only been reported in 3 cases in the literature. Case. A young female suffering from corticoid and methotrexate refractory AOSD was treated by tocilizumab. After 19 months of consecutive treatment, she developed acute severe liver injury. Liver biopsy showed extensive hepatocellular necrosis with ballooned hepatocytes, highly suggestive of drug-induced liver injury. No other relevant drug exposure beside tocilizumab was recorded. She recovered totally after treatment discontinuation and an initial 3-day course of intravenous N-acetylcysteine with normalization of liver function tests after 6 weeks. Conclusion. Acute severe hepatitis can be associated with tocilizumab as documented in this case. Careful monitoring of liver function tests is warranted during tocilizumab treatment.

  10. How Do Enzymes 'Meet' Nanoparticles and Nanomaterials?

    Science.gov (United States)

    Chen, Ming; Zeng, Guangming; Xu, Piao; Lai, Cui; Tang, Lin

    2017-11-01

    Enzymes are fundamental biological catalysts responsible for biological regulation and metabolism. The opportunity for enzymes to 'meet' nanoparticles and nanomaterials is rapidly increasing due to growing demands for applications in nanomaterial design, environmental monitoring, biochemical engineering, and biomedicine. Therefore, understanding the nature of nanomaterial-enzyme interactions is becoming important. Since 2014, enzymes have been used to modify, degrade, or make nanoparticles/nanomaterials, while numerous nanoparticles/nanomaterials have been used as materials for enzymatic immobilization and biosensors and as enzyme mimicry. Among the various nanoparticles and nanomaterials, metal nanoparticles and carbon nanomaterials have received extensive attention due to their fascinating properties. This review provides an overview about how enzymes meet nanoparticles and nanomaterials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. COMPLICATIONS OF ALCOHOLIC LIVER DISEASE AND DIAGNOSTIC MARKERS

    Directory of Open Access Journals (Sweden)

    Milena Ilić

    2011-12-01

    Full Text Available Alcoholism is one of the leading diseases affecting people’s health and immunity worldwide. Nearly 30 thousand people in the USA die from chronic liver damage. The liver is the central organ in the metabolism of alcohol. Alcohol is primarily a hepatotoxic agent. Hepatotoxicity of alcohol is clinically manifested by the development of alcoholic fatty liver, alcoholic hepatitis and alcoholic cirrhosis. It is characterized by appropriate symptomatology, depending on the degree of liver damage. Excessive use of alcohol for a long period of time, along with malnutrition, genetic and ethnic predisposition, leads to alcoholic cirrhosis and the development of its complications. Portal hypertension damages other organs and organ systems, causing hepatopulmonary syndrome, hepatorenal syndrome, hepatic encephalopathy, spontaneous bacterial peritonitis, etc. For these reasons, alcoholism reduction is given priority, as well as reduction of morbidity and mortality of people with alcoholic chronic liver damage. Therefore, early diagnosis of alcohol abuse is necessary, as well as timely diagnosis of different degrees of alcoholic liver damage. The diagnosis of chronic alcoholic liver damage is set on the basis of confirmed data of alcohol consumption; liver function test (serum markers aminotransferase, gammaglutamyl transferase, prothrombin time, serum bilirubin and albumin level; serum markers of liver fibrosis. Fibrosis markers are directly involved in sedimentation and dissolution of extracellular matrix, i.e. in the process of fibrogenesis and fibrinolysis of liver tissues. They include markers and enzymes of metabolism, as well as cytokines and chemokines.

  12. Effects of orally applied butyrate bolus on histone acetylation and cytochrome P450 enzyme activity in the liver of chicken – a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Mátis Gábor

    2013-01-01

    Full Text Available Abstract Background Butyrate is known as histone deacetylase inhibitor, inducing histone hyperacetylation in vitro and playing a predominant role in the epigenetic regulation of gene expression and cell function. We hypothesized that butyrate, endogenously produced by intestinal microbial fermentation or applied as a nutritional supplement, might cause similar in vivo modifications in the chromatin structure of the hepatocytes, influencing the expression of certain genes and therefore modifying the activity of hepatic microsomal drug-metabolizing cytochrome P450 (CYP enzymes. Methods An animal study was carried out in chicken as a model to investigate the molecular mechanisms of butyrate’s epigenetic actions in the liver. Broiler chicks in the early post-hatch period were treated once daily with orally administered bolus of butyrate following overnight starvation with two different doses (0.25 or 1.25 g/kg body weight per day for five days. After slaughtering, cell nucleus and microsomal fractions were separated by differential centrifugation from the livers. Histones were isolated from cell nuclei and acetylation of hepatic core histones was screened by western blotting. The activity of CYP2H and CYP3A37, enzymes involved in biotransformation in chicken, was detected by aminopyrine N-demethylation and aniline-hydroxylation assays from the microsomal suspensions. Results Orally added butyrate, applied in bolus, had a remarkable impact on nucleosome structure of hepatocytes: independently of the dose, butyrate caused hyperacetylation of histone H2A, but no changes were monitored in the acetylation state of H2B. Intensive hyperacetylation of H3 was induced by the higher administered dose, while the lower dose tended to increase acetylation ratio of H4. In spite of the observed modification in histone acetylation, no significant changes were observed in the hepatic microsomal CYP2H and CYP3A37 activity. Conclusion Orally added butyrate in bolus

  13. Liver insulinase and insulin-like activity of the blood plasma in irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhikhareva, A I; Dokshina, G A [Tomskij Gosudarstvennyj Univ. (USSR)

    1975-05-01

    Comparative quantitative analysis of the functional effect of radiation on the activity of liver insulinase of irradiated rats has shown that the insulinase activity of the blood plasma decreases (21-45%) one to three days after the exposure at betatron. Insulinase activity of the liver extracts is also inhibited (16-22%) as compared to intact liver extracts. Twelve days after the exposure and later, insulin-like activity of the plasma and the enzyme activity increase up to 37 per cent.

  14. Liver enzyme abnormalities in taking traditional herbal medicine in Korea: A retrospective large sample cohort study of musculoskeletal disorder patients.

    Science.gov (United States)

    Lee, Jinho; Shin, Joon-Shik; Kim, Me-Riong; Byun, Jang-Hoon; Lee, Seung-Yeol; Shin, Ye-Sle; Kim, Hyejin; Byung Park, Ki; Shin, Byung-Cheul; Lee, Myeong Soo; Ha, In-Hyuk

    2015-07-01

    The objective of this study is to report the incidence of liver injury from herbal medicine in musculoskeletal disease patients as large-scale studies are scarce. Considering that herbal medicine is frequently used in patients irrespective of liver function in Korea, we investigated the prevalence of liver injury by liver function test results in musculoskeletal disease patients. Of 32675 inpatients taking herbal medicine at 7 locations of a Korean medicine hospital between 2005 and 2013, we screened for liver injury in 6894 patients with liver function tests (LFTs) at admission and discharge. LFTs included t-bilirubin, AST, ALT, and ALP. Liver injury at discharge was assessed by LFT result classifications at admission (liver injury, liver function abnormality, and normal liver function). In analyses for risk factors of liver injury at discharge, we adjusted for age, sex, length of stay, conventional medicine intake, HBs antigen/antibody, and liver function at admission. A total 354 patients (prevalence 5.1%) had liver injury at admission, and 217 (3.1%) at discharge. Of the 354 patients with liver injury at admission, only 9 showed a clinically significant increase after herbal medicine intake, and 225 returned to within normal range or showed significant liver function recovery. Out of 4769 patients with normal liver function at admission, 27 (0.6%) had liver injury at discharge. In multivariate analyses for risk factors, younger age, liver function abnormality at admission, and HBs antigen positive were associated with injury at discharge. The prevalence of liver injury in patients with normal liver function taking herbal medicine for musculoskeletal disease was low, and herbal medicine did not exacerbate liver injury in most patients with injury prior to intake. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. ­Characterization of pyruvate kinase from the anoxia tolerant turtle, Trachemys scripta elegans: a potential role for enzyme methylation during metabolic rate depression

    Directory of Open Access Journals (Sweden)

    Amanda M.S. Mattice

    2018-06-01

    Full Text Available Background Pyruvate kinase (PK is responsible for the final reaction in glycolysis. As PK is a glycolytic control point, the analysis of PK posttranslational modifications (PTM and kinetic changes reveals a key piece of the reorganization of energy metabolism in an anoxia tolerant vertebrate. Methods To explore PK regulation, the enzyme was isolated from red skeletal muscle and liver of aerobic and 20-hr anoxia-exposed red eared-slider turtles (Trachemys scripta elegans. Kinetic analysis and immunoblotting were used to assess enzyme function and the corresponding covalent modifications to the enzymes structure during anoxia. Results Both muscle and liver isoforms showed decreased affinity for phosphoenolpyruvate substrate during anoxia, and muscle PK also had a lower affinity for ADP. I50 values for the inhibitors ATP and lactate were lower for PK from both tissues after anoxic exposure while I50 L-alanine was only reduced in the liver. Both isozymes showed significant increases in threonine phosphorylation (by 42% in muscle and 60% in liver and lysine methylation (by 43% in muscle and 70% in liver during anoxia which have been linked to suppression of PK activity in other organisms. Liver PK also showed a 26% decrease in tyrosine phosphorylation under anoxia. Discussion Anoxia responsive changes in turtle muscle and liver PK coordinate with an overall reduced activity state. This reduced affinity for the forward glycolytic reaction is likely a key component of the overall metabolic rate depression that supports long term survival in anoxia tolerant turtles. The coinciding methyl- and phospho- PTM alterations present the mechanism for tissue specific enzyme modification during anoxia.

  16. ­Characterization of pyruvate kinase from the anoxia tolerant turtle, Trachemys scripta elegans: a potential role for enzyme methylation during metabolic rate depression

    Science.gov (United States)

    2018-01-01

    Background Pyruvate kinase (PK) is responsible for the final reaction in glycolysis. As PK is a glycolytic control point, the analysis of PK posttranslational modifications (PTM) and kinetic changes reveals a key piece of the reorganization of energy metabolism in an anoxia tolerant vertebrate. Methods To explore PK regulation, the enzyme was isolated from red skeletal muscle and liver of aerobic and 20-hr anoxia-exposed red eared-slider turtles (Trachemys scripta elegans). Kinetic analysis and immunoblotting were used to assess enzyme function and the corresponding covalent modifications to the enzymes structure during anoxia. Results Both muscle and liver isoforms showed decreased affinity for phosphoenolpyruvate substrate during anoxia, and muscle PK also had a lower affinity for ADP. I50 values for the inhibitors ATP and lactate were lower for PK from both tissues after anoxic exposure while I50 L-alanine was only reduced in the liver. Both isozymes showed significant increases in threonine phosphorylation (by 42% in muscle and 60% in liver) and lysine methylation (by 43% in muscle and 70% in liver) during anoxia which have been linked to suppression of PK activity in other organisms. Liver PK also showed a 26% decrease in tyrosine phosphorylation under anoxia. Discussion Anoxia responsive changes in turtle muscle and liver PK coordinate with an overall reduced activity state. This reduced affinity for the forward glycolytic reaction is likely a key component of the overall metabolic rate depression that supports long term survival in anoxia tolerant turtles. The coinciding methyl- and phospho- PTM alterations present the mechanism for tissue specific enzyme modification during anoxia. PMID:29900073

  17. Hepatitis A infection in patients with chronic viral liver disease: a cross-sectional study in Jahrom, Iran.

    Science.gov (United States)

    Ahmadi Vasmehjani, A; Javeshghani, D; Baharlou, R; Shayestehpour, M; Mousavinasab, S D; Joharinia, N; Enderami, S E

    2015-02-01

    Infection with hepatitis A virus (HAV) in patient with chronic liver disease (CLD; due to hepatitis B or hepatitis C) may cause severe disease and fulminant liver failure. This study aimed to determine the seroprevalence of HAV antibodies in patients infected with HCV or HBV in Iran (Jahrom city). A total of 159 patients with underlying CLD were recruited between September 2012 and February 2013. Serum samples were collected from each patient and tested for anti-HAV using enzyme-linked immunosorbent assay (ELISA). The overall seroprevalence of total anti-HAV was 79·2%. Patients aged 20-30 years had the lowest (28·3%) anti-HAV seropositivity and those aged >50 years had the highest (95%) seropositivity. The overall prevalence of anti-HAV in patients with chronic HCV and HBV infection was 93·7% and 77·1%, respectively. The anti-HAV seropositivity in liver cirrhosis patients was 100% compared to CLD patients. Because of low HAV immunity in younger CLD patients, vaccination against HAV should be considered.

  18. Clinical heterogeneity in autoimmune acute liver failure

    Science.gov (United States)

    Chavez-Tapia, Norberto C; Martinez-Salgado, Julio; Granados, Julio; Uribe, Misael; Tellez-Avila, Felix I

    2007-01-01

    AIM: To describe the outcome and prognosis in a cohort of patients with acute liver failure due to autoimmune hepatitis without liver transplantation. METHODS: A retrospective trial was conducted in 11 patients with acute liver failure due to autoimmune hepatitis who attended the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran. Demographic, biochemical and severity indexes, and treatment and outcome were assessed. RESULTS: Among the 11 patients, with a median age of 31 years, 72% had inflammatory response syndrome, and six patients received corticosteroids. The mortality rate within four weeks was 56%, and the one-year survival was 27%. In the survivors, severity indexes were lower and 83% received corticosteroids. CONCLUSION: We observed a relatively high survival rate in patients with acute liver failure due to autoimmune hepatitis. This survival rate could be influenced by severity of the disease and/or use of corticosteroids. PMID:17465474

  19. Dietary fructose augments ethanol-induced liver pathology.

    Science.gov (United States)

    Thomes, Paul G; Benbow, Jennifer H; Brandon-Warner, Elizabeth; Thompson, Kyle J; Jacobs, Carl; Donohue, Terrence M; Schrum, Laura W

    2017-05-01

    Certain dietary components when combined with alcohol exacerbate alcohol-induced liver injury (ALI). Here, we tested whether fructose, a major ingredient of the western diet, enhances the severity of ALI. We fed mice ethanol for 8 weeks in the following Lieber-DeCarli diets: (a) Regular (contains olive oil); (b) corn oil (contains corn oil); (c) fructose (contains fructose and olive oil) and (d) corn+fructose (contains fructose and corn oil). We compared indices of metabolic function and liver pathology among the different groups. Mice fed fructose-free and fructose-containing ethanol diets exhibited similar levels of blood alcohol, blood glucose and signs of disrupted hepatic insulin signaling. However, only mice given fructose-ethanol diets showed lower insulin levels than their respective controls. Compared with their respective pair-fed controls, all ethanol-fed mice exhibited elevated levels of serum ALT; the inflammatory cytokines TNF-α, MCP-1 and MIP-2; hepatic lipid peroxides and triglycerides. All the latter parameters were significantly higher in mice given fructose-ethanol diets than those fed fructose-free ethanol diets. Mice given fructose-free or fructose-containing ethanol diets each had higher levels of hepatic lipogenic enzymes than controls. However, the level of the lipogenic enzyme fatty acid synthase (FAS) was significantly higher in livers of mice given fructose control and fructose-ethanol diets than in all other groups. Our findings indicate that dietary fructose exacerbates ethanol-induced steatosis, oxidant stress, inflammation and liver injury, irrespective of the dietary fat source, to suggest that inclusion of fructose in or along with alcoholic beverages increases the risk of more severe ALI in heavy drinkers. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme

    Directory of Open Access Journals (Sweden)

    V. Bertone

    2011-02-01

    most hepatocytes were devoid of AlkP activity with the exception of clusters of macrosteatotic hepatocytes in the mid-zone, where the reaction was intense in basolateral domains and in distorted canaliculi, a typical pattern of cholestasis. The interpretation of these data was hindered by the fact that the physiological role of AlkP is still under debate. In the present study, the various functions proposed for the role of the enzyme in bile canaliculi and in cholangiocytes are reviewed. Independently of the AlkP role, our data suggest that AlkP does not seem to be a reliable marker to study the initial step of bile production during OLT of fatty livers, but may still be used to investigate the behaviour of bile ductules and small bile ducts.

  1. Altered alkaline phosphatase activity in obese Zucker rats liver respect to lean Zucker and Wistar rats discussed in terms of all putative roles ascribed to the enzyme.

    Science.gov (United States)

    Bertone, V; Tarantola, E; Ferrigno, A; Gringeri, E; Barni, S; Vairetti, M; Freitas, I

    2011-02-08

    were devoid of AlkP activity with the exception of clusters of macrosteatotic hepatocytes in the mid-zone, where the reaction was intense in basolateral domains and in distorted canaliculi, a typical pattern of cholestasis. The interpretation of these data was hindered by the fact that the physiological role of AlkP is still under debate. In the present study, the various functions proposed for the role of the enzyme in bile canaliculi and in cholangiocytes are reviewed. Independently of the AlkP role, our data suggest that AlkP does not seem to be a reliable marker to study the initial step of bile production during OLT of fatty livers, but may still be used to investigate the behaviour of bile ductules and small bile ducts.

  2. Energy metabolism in the liver.

    Science.gov (United States)

    Rui, Liangyou

    2014-01-01

    The liver is an essential metabolic organ, and its metabolic function is controlled by insulin and other metabolic hormones. Glucose is converted into pyruvate through glycolysis in the cytoplasm, and pyruvate is subsequently oxidized in the mitochondria to generate ATP through the TCA cycle and oxidative phosphorylation. In the fed state, glycolytic products are used to synthesize fatty acids through de novo lipogenesis. Long-chain fatty acids are incorporated into triacylglycerol, phospholipids, and/or cholesterol esters in hepatocytes. These complex lipids are stored in lipid droplets and membrane structures, or secreted into the circulation as very low-density lipoprotein particles. In the fasted state, the liver secretes glucose through both glycogenolysis and gluconeogenesis. During pronged fasting, hepatic gluconeogenesis is the primary source for endogenous glucose production. Fasting also promotes lipolysis in adipose tissue, resulting in release of nonesterified fatty acids which are converted into ketone bodies in hepatic mitochondria though β-oxidation and ketogenesis. Ketone bodies provide a metabolic fuel for extrahepatic tissues. Liver energy metabolism is tightly regulated by neuronal and hormonal signals. The sympathetic system stimulates, whereas the parasympathetic system suppresses, hepatic gluconeogenesis. Insulin stimulates glycolysis and lipogenesis but suppresses gluconeogenesis, and glucagon counteracts insulin action. Numerous transcription factors and coactivators, including CREB, FOXO1, ChREBP, SREBP, PGC-1α, and CRTC2, control the expression of the enzymes which catalyze key steps of metabolic pathways, thus controlling liver energy metabolism. Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases. © 2014 American Physiological Society.

  3. Hyperdensity liver tumor on plain CT

    Energy Technology Data Exchange (ETDEWEB)

    Hirota, Shozo; Hanaguri, Katsuro [Kochi Municipal Central Hospital (Japan); Shimizu, Masahumi; Sako, Masao; Harada, Yasushi

    1984-12-01

    Most liver tumors on plain CT have been recognized as low density or iso-density masses. Sometimes calcified high density masses were shown on plain CT in case of cysts or metastatic liver tumors. However, hyperdensity mass of the liver on CT, of which the density was a little higher than surrounding tissues, was very rare. Recently 7 patients with hyperdensity liver masses on plain CT were experienced: 6 hepatocellular carcinomas and 1 hepatic cavernous hemangioma. A single hyperdensity mass was shown in 4 patients, a hyperdensity mass of multiple hepatic tumors was shown in 2 patients, and some hyperdensity masses of multiple hepatic tumors were shown in 1 patient. Lesions are classified in 3 types according to the appearance of hyperdensity masses: diffuse hyperdensity all over the mass, ring like hyperdensity, creascent like hyperdensity. Intravenous contrast enhancement was performed in 2 patients: one with a primary hepatocellular carcinoma, and another with a hepatic cavernous hemangioma. In the former case the tumor margin had changed unclear, in the latter case the tumor was markedly enhanced. Our results revealed that hyperdensity liver tumors were divided into 2 types: One type, shown in a cavernous hemangioma with fatty liver, demonstrated relative hyperdensity due to lower density of the surrounding tissue. Another type, shown in 6 hepatocellular carcinomas, showed hyperdensity since the density of the tumor was hyperdensity relative to the surrounding tissue of the liver. It was suggested that the tumor with the latter type had been strongly probable of malignant one, and been recommended to receive further examination. Cause of hyperdensity was thought to be due to hemorrhage, though microcalcification could not be denyed. In Japan, no hyperdensity liver tumor had been reported partly due to a wide window width with which CT photographs were taken.

  4. Acute metabolic decompensation due to influenza in a mouse model of ornithine transcarbamylase deficiency

    Directory of Open Access Journals (Sweden)

    Peter J. McGuire

    2014-02-01

    Full Text Available The urea cycle functions to incorporate ammonia, generated by normal metabolism, into urea. Urea cycle disorders (UCDs are caused by loss of function in any of the enzymes responsible for ureagenesis, and are characterized by life-threatening episodes of acute metabolic decompensation with hyperammonemia (HA. A prospective analysis of interim HA events in a cohort of individuals with ornithine transcarbamylase (OTC deficiency, the most common UCD, revealed that intercurrent infection was the most common precipitant of acute HA and was associated with markers of increased morbidity when compared with other precipitants. To further understand these clinical observations, we developed a model system of metabolic decompensation with HA triggered by viral infection (PR8 influenza using spf-ash mice, a model of OTC deficiency. Both wild-type (WT and spf-ash mice displayed similar cytokine profiles and lung viral titers in response to PR8 influenza infection. During infection, spf-ash mice displayed an increase in liver transaminases, suggesting a hepatic sensitivity to the inflammatory response and an altered hepatic immune response. Despite having no visible pathological changes by histology, WT and spf-ash mice had reduced CPS1 and OTC enzyme activities, and, unlike WT, spf-ash mice failed to increase ureagenesis. Depression of urea cycle function was seen in liver amino acid analysis, with reductions seen in aspartate, ornithine and arginine during infection. In conclusion, we developed a model system of acute metabolic decompensation due to infection in a mouse model of a UCD. In addition, we have identified metabolic perturbations during infection in the spf-ash mice, including a reduction of urea cycle intermediates. This model of acute metabolic decompensation with HA due to infection in UCD serves as a platform for exploring biochemical perturbations and the efficacy of treatments, and could be adapted to explore acute decompensation in other

  5. Modulation of nuclear T3 binding by T3 in a human hepatocyte cell-line (Chang-liver) - T3 stimulation of cell growth but not of malic enzyme, glucose-6-phosphatdehydrogenase or 6-phosphogluconate-dehydrogenase

    DEFF Research Database (Denmark)

    Matzen, L E; Kristensen, S R; Kvetny, J

    1991-01-01

    The T3 modulation of nuclear T3 binding (NBT3), the T3 effect on cell growth, and the T3 and insulin effects on malic enzyme (ME), glucose-6-phosphat-dehydrogenase (G6PD) and 6-phosphogluconat-dehydrogenase (G6PD) were studied in a human hepatocyte cell-line (Chang-liver). T3 was bound to a high ...

  6. Beneficial mechanisms of aerobic exercise on hepatic lipid metabolism in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Guo, Rui; Liong, Emily C; So, Kwok Fai; Fung, Man-Lung; Tipoe, George L

    2015-04-01

    Non-alcoholic fatty liver disease (NAFLD) refers to any fatty liver disease that is not due to excessive use of alcohol. NAFLD probably results from abnormal hepatic lipid metabolism and insulin resistance. Aerobic exercise is shown to improve NAFLD. This review aimed to evaluate the molecular mechanisms involved in the beneficial effects of aerobic exercise on NAFLD. We searched articles in English on the role of aerobic exercise in NAFLD therapy in PubMed. The mechanisms of chronic aerobic exercise in regulating the outcome of NAFLD include: (i) reducing intrahepatic fat content by down-regulating sterol regulatory element-binding protein-1c and up-regulating peroxisome proliferator-activated receptor gamma expression levels; (ii) decreasing hepatic oxidative stress through modulating the reactive oxygen species, and enhancing antioxidant enzymes such as catalase and glutathione peroxidase; (iii) ameliorating hepatic inflammation via the inhibition of pro-inflammatory mediators such as tumor necrosis factor-alpha and interleukin-1 beta; (iv) attenuating mitochondrial dependent apoptosis by reducing cytochrome C released from the mitochondria to the cytosol; and (v) inducing hepato-protective autophagy. Aerobic exercise, via different mechanisms, significantly decreases the fat content of the liver and improves the outcomes of patients with NAFLD.

  7. Roles of different forms of cytochrome P450 in the activation of the promutagen 6-aminochrysene to genotoxic metabolites in human liver microsomes.

    Science.gov (United States)

    Yamazaki, H; Mimura, M; Oda, Y; Inui, Y; Shiraga, T; Iwasaki, K; Guengerich, F P; Shimada, T

    1993-07-01

    We reported previously that the potent mutagen 6-aminochrysene is catalyzed principally by rat liver microsomal P4501A and P4502B enzymes to reactive metabolites that induce umu gene expression in O-acetyltransferase-over-expressing strain Salmonella typhimurium NM2009; the proposal was made that there are different mechanisms in the formation of reactive N-hydroxylated and diolepoxide metabolites by P450 enzymes (Yamazaki, H. and Shimada, T., Biochem. Pharmacol., 44, 913-920, 1992). Here we further examined the roles of human liver P450 enzymes and the mechanism of activation of 6-aminochrysene by rat and human P450 enzymes in the Salmonella tester strains. Liver microsomes from 18 different human samples catalyzed activation of 6-aminochrysene more efficiently in S. typhimurium NM2009 than in the original strain of S. typhimurium TA1535/pSK1002. The rates of 6-aminochrysene activation in 18 human liver samples showed good correlation to the contents of P4502B6 as well as contents of P4503A4 and the respective mono-oxygenase activities catalyzed by P4503A4. Among purified P450 enzymes examined, P4501A2 as well as P4503A4 were highly active in transforming 6-amino-chrysene to reactive metabolites, suggesting the involvement of different human P450 enzymes in the reaction. Four human samples that contained relatively high levels of particular P450 enzymes in their microsomes were selected and used for further characterization. Liver microsomes from human samples HL-13 and HL-4 that contained the highest levels of P4502B6 and P4503A4 respectively, were sensitive to the respective antibodies raised against monkey P4502B and human P4503A4; the activity in sample HL-16 having the highest level of P4501A2 was inhibited by anti-P4501A2 IgG. alpha-Naphthoflavone enhanced the activation of 6-aminochrysene very significantly in human liver microsomes enriched in P4503A4 and P4502B6 enzymes. Pentachlorophenol, an inhibitor of acetyltransferase activity, suppressed the

  8. Renoprotective effect of crocin following liver ischemia/ reperfusion injury in Wistar rats

    Directory of Open Access Journals (Sweden)

    Seyyed Ali Mard

    2017-10-01

    Full Text Available Objective(s: The objectives of the current study were to evaluate the effects of hepatic ‎ischemia/reperfusion (IR injury on the activity of antioxidant enzymes, biochemical factors, and ‎histopathological changes in rat kidney, and to investigate the effect of crocin on IR-‎related changes. Materials and Methods: Thirty-two male Wistar rats were randomly allocated into four groups (n=8. They were ‎sham-operated, IR, crocin pre-treatment, and crocin pretreatment+IR groups. Sham-operated ‎and Crocin pre-treatment groups received normal saline (N/S, 2 ml/day and crocin (200 mg/kg ‎for seven consecutive days intraperitoneally (IP, respectively, then rats underwent laparotomy, only. ‎IR and crocin pretreatment+IR groups received N/S and crocin with the same dose, time, and route, ‎respectively, then rats underwent partial (70% ischemia for 45 min that was followed by reperfusion ‎for 60 min. At the end of the experiment, kidney specimens were taken for histopathological and ‎antioxidant evaluations and also blood samples were obtained for biochemical analysis. Results: The results of the present study showed that crocin pre-treatment significantly increased ‎the activity of antioxidants, decreased the serum levels of liver enzymes and blood urea nitrogen ‎following IR-induced hepatic injury. Crocin also ameliorated kidney´s histopathological ‎disturbance beyond IR-induced hepatic injury. Conclusion: Crocin as an antioxidant agent protected renal insult following liver IR injury by ‎increasing the activity of antioxidant enzymes, reducing serum levels of liver enzymes, and ‎improving histopathological changes.‎

  9. Erythrocytes Membrane Alterations Reflecting Liver Damage in CCl₄-Induced Cirrhotic Rats: The Ameliorative Effect of Naltrexone

    Directory of Open Access Journals (Sweden)

    Fatemeh Sarhadi Kholari

    2016-11-01

    Full Text Available Cirrhosis is the consequence of chronic liver disease. Deleterious effects of oxidative stress on hepatocytes may be reflected in the erythrocyte membrane. Naltrexone (NTX has been shown to attenuate hepatocellular injury in fibrotic animal models. The aim of this study was to investigate the progressive effect of CCl4 on the liver and whether the improvement of liver cirrhosis can be monitored through alterations in the erythrocyte membrane. In this study, 84 male Wistar rats were divided into 4 groups and received reagents (i.p. as follows: 1- CCl₄, 2- NTX + CCl₄, 3- Mineral Oil (M, and 4- NTX + M. After 2, 6 and 8 weeks, the blood and liver tissue samples were collected. Plasma enzyme activities, the content of erythrocyte GSH and some membrane compositions, including protein carbonyl, protein sulfhydryl, and malondialdehyde were assessed. After 6 and 8 weeks, plasma enzyme activities and the content of protein carbonyl were higher in CCl4 group significantly, as compared to other groups (P<0.001. NTX significantly diminished protein carbonyl and plasma enzyme activities (P<0.001. GSH did not change until the 6th week. However, CCl4+NTX increased it significantly as compared to CCl₄ group (P<0.05. Protein sulfhydryl showed changes in NTX+CCl₄ group which indicated a significant increase in protein sulfhydryl content in a 6th week compared to CCl4 group (P<0.05. MDA did not show any significant alteration. CCl₄-induced cirrhosis is accompanied by increased content of oxidative stress markers, especially protein carbonyl of RBC membrane and plasma enzyme activities. This study shows that the progression of liver cirrhosis and the ameliorative effect of NTX can be followed through alterations of these markers.

  10. Isolation and characterization of adult human liver progenitors from ischemic liver tissue derived from therapeutic hepatectomies.

    Science.gov (United States)

    Stachelscheid, Harald; Urbaniak, Thomas; Ring, Alexander; Spengler, Berlind; Gerlach, Jörg C; Zeilinger, Katrin

    2009-07-01

    Recent evidence suggests that progenitor cells in adult tissues and embryonic stem cells share a high resistance to hypoxia and ischemic stress. To study the ischemic resistance of adult liver progenitors, we characterized remaining viable cells in human liver tissue after cold ischemic treatment for 24-168 h, applied to the tissue before cell isolation. In vitro cultures of isolated cells showed a rapid decline of the number of different cell types with increasing ischemia length. After all ischemic periods, liver progenitor-like cells could be observed. The comparably small cells exhibited a low cytoplasm-to-nucleus ratio, formed densely packed colonies, and showed a hepatobiliary marker profile. The cells expressed epithelial cell adhesion molecule, epithelial-specific (CK8/18) and biliary-specific (CK7/19) cytokeratins, albumin, alpha-1-antitrypsin, cytochrome-P450 enzymes, as well as weak levels of hepatocyte nuclear factor-4 and gamma-glutamyl transferase, but not alpha-fetoprotein or Thy-1. In vitro survival and expansion was facilitated by coculture with mouse embryonic fibroblasts. Hepatic progenitor-like cells exhibit a high resistance to ischemic stress and can be isolated from human liver tissue after up to 7 days of ischemia. Ischemic liver tissue from various sources, thought to be unsuitable for cell isolation, may be considered as a prospective source of hepatic progenitor cells.

  11. Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy

    Directory of Open Access Journals (Sweden)

    Fuyang Zhang

    2016-11-01

    Full Text Available The Western meat-rich diet is both high in protein and fat. Although the hazardous effect of a high fat diet (HFD upon liver structure and function is well recognized, whether the co-presence of high protein intake contributes to, or protects against, HF-induced hepatic injury remains unclear. Increased intake of branched chain amino acids (BCAA, essential amino acids compromising 20% of total protein intake reduces body weight. However, elevated circulating BCAA is associated with non-alcoholic fatty liver disease and injury. The mechanisms responsible for this quandary remain unknown; the role of BCAA in HF-induced liver injury is unclear. Utilizing HFD or HFD + BCAA models, we demonstrated BCAA supplementation attenuated HFD-induced weight gain, decreased fat mass, activated mammalian target of rapamycin (mTOR, inhibited hepatic lipogenic enzymes, and reduced hepatic triglyceride content. However, BCAA caused significant hepatic damage in HFD mice, evidenced by exacerbated hepatic oxidative stress, increased hepatic apoptosis, and elevated circulation hepatic enzymes. Compared to solely HFD-fed animals, plasma levels of free fatty acids (FFA in the HFD + BCAA group are significantly further increased, due largely to AMPKα2-mediated adipocyte lipolysis. Lipolysis inhibition normalized plasma FFA levels, and improved insulin sensitivity. Surprisingly, blocking lipolysis failed to abolish BCAA-induced liver injury. Mechanistically, hepatic mTOR activation by BCAA inhibited lipid-induced hepatic autophagy, increased hepatic apoptosis, blocked hepatic FFA/triglyceride conversion, and increased hepatocyte susceptibility to FFA-mediated lipotoxicity. These data demonstrated that BCAA reduces HFD-induced body weight, at the expense of abnormal lipolysis and hyperlipidemia, causing hepatic lipotoxicity. Furthermore, BCAA directly exacerbate hepatic lipotoxicity by reducing lipogenesis and inhibiting autophagy in the hepatocyte.

  12. Liver Inflammation and Metabolic Signaling in ApcMin/+ Mice: The Role of Cachexia Progression

    Science.gov (United States)

    Narsale, Aditi A.; Enos, Reilly T.; Puppa, Melissa J.; Chatterjee, Saurabh; Murphy, E. Angela; Fayad, Raja; Pena, Majorette O’; Durstine, J. Larry; Carson, James A.

    2015-01-01

    The ApcMin/+ mouse exhibits an intestinal tumor associated loss of muscle and fat that is accompanied by chronic inflammation, insulin resistance and hyperlipidemia. Since the liver governs systemic energy demands through regulation of glucose and lipid metabolism, it is likely that the liver is a pathological target of cachexia progression in the ApcMin/+ mouse. The purpose of this study was to determine if cancer and the progression of cachexia affected liver endoplasmic reticulum (ER)-stress, inflammation, metabolism, and protein synthesis signaling. The effect of cancer (without cachexia) was examined in wild-type and weight-stable ApcMin/+ mice. Cachexia progression was examined in weight-stable, pre-cachectic, and severely-cachectic ApcMin/+ mice. Livers were analyzed for morphology, glycogen content, ER-stress, inflammation, and metabolic changes. Cancer induced hepatic expression of ER-stress markers BiP (binding immunoglobulin protein), IRE-1α (endoplasmic reticulum to nucleus signaling 1), and inflammatory intermediate STAT-3 (signal transducer and activator of transcription 3). While gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was suppressed by cancer, glycogen content or protein synthesis signaling remained unaffected. Cachexia progression depleted liver glycogen content and increased mRNA expression of glycolytic enzyme PFK (phosphofrucktokinase) and gluconeogenic enzyme PEPCK. Cachexia progression further increased pSTAT-3 but suppressed p-65 and JNK (c-Jun NH2-terminal kinase) activation. Interestingly, progression of cachexia suppressed upstream ER-stress markers BiP and IRE-1α, while inducing its downstream target CHOP (DNA-damage inducible transcript 3). Cachectic mice exhibited a dysregulation of protein synthesis signaling, with an induction of p-mTOR (mechanistic target of rapamycin), despite a suppression of Akt (thymoma viral proto-oncogene 1) and S6 (ribosomal protein S6) phosphorylation. Thus, cancer

  13. Liver inflammation and metabolic signaling in ApcMin/+ mice: the role of cachexia progression.

    Directory of Open Access Journals (Sweden)

    Aditi A Narsale

    Full Text Available The ApcMin/+ mouse exhibits an intestinal tumor associated loss of muscle and fat that is accompanied by chronic inflammation, insulin resistance and hyperlipidemia. Since the liver governs systemic energy demands through regulation of glucose and lipid metabolism, it is likely that the liver is a pathological target of cachexia progression in the ApcMin/+ mouse. The purpose of this study was to determine if cancer and the progression of cachexia affected liver endoplasmic reticulum (ER-stress, inflammation, metabolism, and protein synthesis signaling. The effect of cancer (without cachexia was examined in wild-type and weight-stable ApcMin/+ mice. Cachexia progression was examined in weight-stable, pre-cachectic, and severely-cachectic ApcMin/+ mice. Livers were analyzed for morphology, glycogen content, ER-stress, inflammation, and metabolic changes. Cancer induced hepatic expression of ER-stress markers BiP (binding immunoglobulin protein, IRE-1α (endoplasmic reticulum to nucleus signaling 1, and inflammatory intermediate STAT-3 (signal transducer and activator of transcription 3. While gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK mRNA expression was suppressed by cancer, glycogen content or protein synthesis signaling remained unaffected. Cachexia progression depleted liver glycogen content and increased mRNA expression of glycolytic enzyme PFK (phosphofrucktokinase and gluconeogenic enzyme PEPCK. Cachexia progression further increased pSTAT-3 but suppressed p-65 and JNK (c-Jun NH2-terminal kinase activation. Interestingly, progression of cachexia suppressed upstream ER-stress markers BiP and IRE-1α, while inducing its downstream target CHOP (DNA-damage inducible transcript 3. Cachectic mice exhibited a dysregulation of protein synthesis signaling, with an induction of p-mTOR (mechanistic target of rapamycin, despite a suppression of Akt (thymoma viral proto-oncogene 1 and S6 (ribosomal protein S6 phosphorylation. Thus

  14. Increased Nitroxidative Stress Promotes Mitochondrial Dysfunction in Alcoholic and Nonalcoholic Fatty Liver Disease

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    Byoung-Joon Song

    2013-01-01

    Full Text Available Increased nitroxidative stress causes mitochondrial dysfunctions through oxidative modifications of mitochondrial DNA, lipids, and proteins. Persistent mitochondrial dysfunction sensitizes the target cells/organs to other pathological risk factors and thus ultimately contributes to the development of more severe disease states in alcoholic and nonalcoholic fatty liver disease. The incidences of nonalcoholic fatty liver disease continuously increase due to high prevalence of metabolic syndrome including hyperlipidemia, hypercholesterolemia, obesity, insulin resistance, and diabetes. Many mitochondrial proteins including the enzymes involved in fat oxidation and energy supply could be oxidatively modified (including S-nitrosylation/nitration under increased nitroxidative stress and thus inactivated, leading to increased fat accumulation and ATP depletion. To demonstrate the underlying mechanism(s of mitochondrial dysfunction, we employed a redox proteomics approach using biotin-N-maleimide (biotin-NM as a sensitive biotin-switch probe to identify oxidized Cys residues of mitochondrial proteins in the experimental models of alcoholic and acute liver disease. The aims of this paper are to briefly describe the mechanisms, functional consequences, and detection methods of mitochondrial dysfunction. We also describe advantages and limitations of the Cys-targeted redox proteomics method with alternative approaches. Finally, we discuss various applications of this method in studying oxidatively modified mitochondrial proteins in extrahepatic tissues or different subcellular organelles and translational research.

  15. Liver tissue tolerance for irradiation : Experimental and clinical investigations

    NARCIS (Netherlands)

    Cromheecke, M; Konings, AWT; Szabo, BG; Hoekstra, HJ

    2000-01-01

    Radiation treatment of the liver for malignant disease has gained renewed interest due to newly developed treatment modalities. Still limited specific knowledge is available concerning liver damage following irradiation. Inconsistencies between reported animal experimental studies are largely due to

  16. Comparison of the relative contributions of intra-abdominal and liver fat to components of the metabolic syndrome

    DEFF Research Database (Denmark)

    Kotronen, Anna; Yki-Järvinen, Hannele; Sevastianova, Ksenia

    2011-01-01

    insulin sensitivity independent of age, gender, subcutaneous (SC) fat, and/or lean body mass (LBM). Including both liver and IA fat, liver and IA fat both explained variation in TG, HDL cholesterol, insulin and hepatic insulin sensitivity independent of each other and of age, gender, SC fat, and LBM....... Liver fat independently predicted glucose and liver enzymes. SC fat and age explained variation in blood pressure. In conclusion, both IA and liver fat independently of each other explain variation in serum TG, HDL cholesterol, insulin concentrations and hepatic insulin sensitivity, thus supporting...

  17. Hepatoprotective effect of collagen peptides from cod skin against liver oxidative damage in vitro and in vivo.

    Science.gov (United States)

    Han, Yantao; Xie, Jing; Gao, Hui; Xia, Yunqiu; Chen, Xuehong; Wang, Chunbo

    2015-03-01

    The objective of this study was to investigate the hepatoprotective effect of cod skin collagen peptides (CSCP), isolated from fishing industrial by-products, in vitro and in vivo. Effect of CSCP on cell proliferation of normal and H2O2-damaged Chang liver cells was determined by MTT assay in vitro. Two animal models, CCl4-induced and acetaminophenum-induced acute hepatotoxicity, were established to assess the hepatoprotective effect of CSCP. Liver weight index, serum ALT and AST, antioxidant enzymes, and lipid peroxidation product were used as the markers of liver toxicity. The cell viability in the H2O2-treated Chang liver cells was remarkably increased when pretreated with CSCP from 100 to 1,000 µg/ml in a dose-dependent manner. CSCP pretreatment also alleviated the CCL4-induced liver index loss, while no marked changes were found in acetaminophenum-treated mice. Furthermore, CSCP pulled down serum ALT and AST level, increased the activities of SOD and CAT, and decreased MDA in both murine models of acute liver toxicity. Pretreatment with CSCP protected liver tissue against oxidative injure in vivo and in vitro. The underlying mechanism might involve enhancement in the activities of antioxidant enzymes and reduction in the lipid peroxidation.

  18. Influence of dark chocolate administration on uric acid, liver ...

    African Journals Online (AJOL)

    Objective. To assess the influence of dark chocolate administration on uric acid, liver enzymes, glucose and lactate responses to summaximal exercise test in male swimmers. Subjects. Eleven competitive swimmers from the athletic club Academic, Sofia volunteered for the study. Design. A randomised study of two periods ...

  19. Humanizing π-class glutathione S-transferase regulation in a mouse model alters liver toxicity in response to acetaminophen overdose.

    Directory of Open Access Journals (Sweden)

    Matthew P Vaughn

    Full Text Available Glutathione S-transferases (GSTs metabolize drugs and xenobiotics. Yet despite high protein sequence homology, expression of π-class GSTs, the most abundant of the enzymes, varies significantly between species. In mouse liver, hepatocytes exhibit high mGstp expression, while in human liver, hepatocytes contain little or no hGSTP1 mRNA or hGSTP1 protein. π-class GSTs are known to be critical determinants of liver responses to drugs and toxins: when treated with high doses of acetaminophen, mGstp1/2+/+ mice suffer marked liver damage, while mGstp1/2-/- mice escape liver injury.To more faithfully model the contribution of π-class GSTs to human liver toxicology, we introduced hGSTP1, with its exons, introns, and flanking sequences, into the germline of mice carrying disrupted mGstp genes. In the resultant hGSTP1+mGstp1/2-/- strain, π-class GSTs were regulated differently than in wild-type mice. In the liver, enzyme expression was restricted to bile duct cells, Kupffer cells, macrophages, and endothelial cells, reminiscent of human liver, while in the prostate, enzyme production was limited to basal epithelial cells, reminiscent of human prostate. The human patterns of hGSTP1 transgene regulation were accompanied by human patterns of DNA methylation, with bisulfite genomic sequencing revealing establishment of an unmethylated CpG island sequence encompassing the gene promoter. Unlike wild-type or mGstp1/2-/- mice, when hGSTP1+mGstp1/2-/- mice were overdosed with acetaminophen, liver tissues showed limited centrilobular necrosis, suggesting that π-class GSTs may be critical determinants of toxin-induced hepatocyte injury even when not expressed by hepatocytes.By recapitulating human π-class GST expression, hGSTP1+mGstp1/2-/- mice may better model human drug and xenobiotic toxicology.

  20. Influence of Chloramphenicol and Amoxicillin on Rat Liver ...

    African Journals Online (AJOL)

    This study examined the effect of chloramphenicol and amoxicillin on liver microsomal enzymes Ca2+-ATPase and Glucose-6-Phosphatase (G-6-P) and lipid peroxidation in rats. Male Wistar strain rats weighing 120 – 195 g were divided into four groups. Group one, the control group, received physiological saline, group ...

  1. Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease.

    Science.gov (United States)

    Payne, Felicity; Lim, Koini; Girousse, Amandine; Brown, Rebecca J; Kory, Nora; Robbins, Ann; Xue, Yali; Sleigh, Alison; Cochran, Elaine; Adams, Claire; Dev Borman, Arundhati; Russel-Jones, David; Gorden, Phillip; Semple, Robert K; Saudek, Vladimir; O'Rahilly, Stephen; Walther, Tobias C; Barroso, Inês; Savage, David B

    2014-06-17

    Phosphatidylcholine (PC) is the major glycerophospholipid in eukaryotic cells and is an essential component in all cellular membranes. The biochemistry of de novo PC synthesis by the Kennedy pathway is well established, but less is known about the physiological functions of PC. We identified two unrelated patients with defects in the Kennedy pathway due to biallellic loss-of-function mutations in phosphate cytidylyltransferase 1 alpha (PCYT1A), the rate-limiting enzyme in this pathway. The mutations lead to a marked reduction in PCYT1A expression and PC synthesis. The phenotypic consequences include some features, such as severe fatty liver and low HDL cholesterol levels, that are predicted by the results of previously reported liver-specific deletion of murine Pcyt1a. Both patients also had lipodystrophy, severe insulin resistance, and diabetes, providing evidence for an additional and essential role for PCYT1A-generated PC in the normal function of white adipose tissue and insulin action.

  2. Enhanced Glucose Uptake in Human Liver Cells and Inhibition of Carbohydrate Hydrolyzing Enzymes by Nordic Berry Extracts

    Directory of Open Access Journals (Sweden)

    Giang Thanh Thi Ho

    2017-10-01

    Full Text Available A Western lifestyle with low physical activity and a diet rich in sugar, fat and processed food contribute to higher incidences of diabetes and obesity. Enhanced glucose uptake in human liver cells was observed after treatment with phenolic extracts from different Nordic berries. All berry extracts showed higher inhibition against α-amylase and α-glucosidase than the anti-diabetic agent acarbose. Total phenolic content and phenolic profiles in addition to antioxidant activities, were also investigated. The berries were extracted with 80% methanol on an accelerated solvent extraction system (ASE and then purified by C-18 solid phase extraction (SPE. Among the ASE methanol extracts, black chokeberry, crowberry and elderberry extracts showed high stimulation of glucose uptake in HepG2 cells and also considerable inhibitory effect towards carbohydrate hydrolyzing enzymes. SPE extracts with higher concentrations of phenolics, resulted in increased glucose uptake and enhanced inhibition of α-amylase and α-glucosidase compared to the ASE extracts. Crowberry and cloudberry were the most potent 15-lipoxygenase inhibitors, while bog whortleberry and lingonberry were the most active xanthine oxidase inhibitors. These results increase the value of these berries as a component of a healthy Nordic diet and have a potential benefit against diabetes.

  3. Effect of Various Diets on the Expression of Phase-I Drug Metabolizing Enzymes in Livers of Mice

    Science.gov (United States)

    Guo, Ying; Cui, Julia Yue; Lu, Hong; Klaassen, Curtis D.

    2017-01-01

    Previous studies have shown that diets can alter the metabolism of drugs; however, it is difficult to compare the effects of multiple diets on drug metabolism among different experimental settings. Phase-I related genes play a major role in the biotransformation of pro-drugs and drugs.In the current study, effects of nine diets on the mRNA expression of phase-I drug-metabolizing enzymes in livers of mice were simultaneously investigated. Compared to the AIN-93M purified diet (control), 73 of the 132 critical phase-I drug metabolizing genes were differentially regulated by at least one diet. Diet restriction produced the most number of changed genes (51), followed by the atherogenic diet (27), high-fat diet (25), standard rodent chow (21), western diet (20), high-fructose diet (5), EFA deficient diet (3), and low n-3 FA diet (1). The mRNAs of the Fmo family changed most, followed by Cyp2b and 4a subfamilies, as well as Por (From 1121 to 21-fold increase of theses mRNAs). There were 59 genes not altered by any of these diets.The present results may improve the interpretation of studies with mice and aid in determining effective and safe doses for individuals with different nutritional diets. PMID:25733028

  4. Stabilization of enzymes in ionic liquids via modification of enzyme charge.

    Science.gov (United States)

    Nordwald, Erik M; Kaar, Joel L

    2013-09-01

    Due to the propensity of ionic liquids (ILs) to inactivate enzymes, the development of strategies to improve enzyme utility in these solvents is critical to fully exploit ILs for biocatalysis. We have developed a strategy to broadly improve enzyme utility in ILs based on elucidating the effect of charge modifications on the function of enzymes in IL environments. Results of stability studies in aqueous-IL mixtures indicated a clear connection between the ratio of enzyme-containing positive-to-negative sites and enzyme stability in ILs. Stability studies of the effect of [BMIM][Cl] and [EMIM][EtSO4 ] on chymotrypsin specifically found an optimum ratio of positively-charged amine-to-negatively-charged acid groups (0.39). At this ratio, the half-life of chymotrypsin was increased 1.6- and 4.3-fold relative to wild-type chymotrypsin in [BMIM][Cl] and [EMIM][EtSO4 ], respectively. The half-lives of lipase and papain were similarly increased as much as 4.0 and 2.4-fold, respectively, in [BMIM][Cl] by modifying the ratio of positive-to-negative sites of each enzyme. More generally, the results of stability studies found that modifications that reduce the ratio of enzyme-containing positive-to-negative sites improve enzyme stability in ILs. Understanding the impact of charge modification on enzyme stability in ILs may ultimately be exploited to rationally engineer enzymes for improved function in IL environments. Copyright © 2013 Wiley Periodicals, Inc.

  5. Radiation induced liver disease: A clinical update

    International Nuclear Information System (INIS)

    Benson, R.; Madan, R.; Chander, S.; Kilambi, R.

    2016-01-01

    Radiation-induced liver disease (RILD) or radiation hepatitis is a sub-acute form of liver injury due to radiation. It is one of the most dreaded complications of radiation which prevents radiation dose escalation and re irradiation for hepatobiliary or upper gastrointestinal malignancies. This complication should be kept in mind whenever a patient is planned for irradiation of these malignancies. Although, incidence of RILD is decreasing due to better knowledge of liver tolerance, improved investigation modalities and modern radiation delivery techniques, treatment options are still limited. In this review article, we have focussed on pathophysiology, risk factors, prevention and management of RILD

  6. Exercise-induced regulation of key factors in substrate choice and gluconeogenesis in mouse liver

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet; Biensø, Rasmus Sjørup; Hassing, Helle Adser

    2015-01-01

    As the demand for hepatic glucose production increases during exercise, regulation of liver substrate choice and gluconeogenic activity becomes essential. The aim of the present study was to investigate the effect of a single exercise bout on gluconeogenic protein content and regulation of enzymes...... involved in substrate utilization in the liver. Mice were subjected to 1 h of treadmill exercise, and livers were removed immediately, 4 or 10 h after exercise. Glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxylase (PEPCK) mRNA contents in the liver increased immediately after exercise, while...... phosphorylation decreased immediately after exercise may indicate that carbohydrates rather than fatty acids are utilized for oxidation in the liver during non-exhaustive exercise....

  7. Shanxi Aged Vinegar Protects against Alcohol-Induced Liver Injury via Activating Nrf2-Mediated Antioxidant and Inhibiting TLR4-Induced Inflammatory Response

    Directory of Open Access Journals (Sweden)

    Ting Xia

    2018-06-01

    Full Text Available Shanxi aged vinegar (SAV is a typical fermented and antioxidant food, which has various health-promoting effects. This work aimed to explore the effects of SAV on alcohol-induced liver injury. A mice model of alcoholic liver injury was established to illuminate its potential mechanisms. All mice pretreated with SAV and then received an ethanol solution (50% w/v, 4.8 g/kg b.w.. The results showed that SAV ameliorated alcohol-induced histological changes and elevation of liver enzymes. SAV attenuated alcohol-induced oxidative stress by declining levels of hepatic oxidants, and restoring depletion of antioxidant enzyme activities in mice livers. Moreover, SAV alleviated alcohol-induced oxidative damage by activating nuclear factor erythroid-2-related factor 2 (Nrf2-mediated signal pathway. In addition, SAV prevented alcohol-induced inflammation by suppressing lipopolysaccharide (LPS level and activities of pro-inflammatory enzymes, and regulating inflammatory cytokines. SAV inhibited alcohol-induced inflammation through down-regulating the expression of Toll-like receptor 4 (TLR4-mediated inflammatory response. The findings provide crucial evidence for elucidating the hepatoprotective mechanisms of SAV and encourage the future application of SAV as a functional food for liver protection.

  8. Characteristics and significance of D-tagatose-induced liver enlargement in rats: An interpretative review.

    Science.gov (United States)

    Bär, A

    1999-04-01

    This review addresses the issue of asymptomatic liver enlargement in rats. It was necessitated by the observation of significantly increased liver weights in rats fed diets with 10 to 20% D-tagatose, a potential new bulk sweetener, for between 28 and 90 days. Increases of liver size without accompanying histopathological changes or impairment of organ function have been observed in rats in response to the ingestion of various xenobiotic compounds (including some food additives), changes of dietary composition (e.g. , high doses of fructose and sucrose), metabolic aberrations (e.g., diabetes), as well as normal pregnancy and lactation. The underlying mechanism(s) are not yet understood in detail but peroxisome proliferation, microsomal enzyme induction, increased storage of glycogen or lipids, and hyperfunction due to an excessive workload are well-established causes of hepatomegaly in rats. In D-tagatose- and fructose-fed rats, a treatment-related increase of hepatic glycogen storage was identified as a likely cause of the liver enlargement. Dietary levels of 5% and about 15-20% were determined as no-effect levels (NOEL) for D-tagatose- and fructose-induced liver enlargement, respectively. At doses above the NOEL, D-tagatose is about four times more efficient than fructose in inducing liver enlargement. On the other hand, the estimated intake of D-tagatose from its intended uses in food is about four times lower than the actual fructose intake. Consequently, a similar safety margin would apply for both sugars. Considering the similarity of the liver effects in rats of fructose, a safe food ingredient, and D-tagatose, the absence of histopathological changes in rats fed a diet with 20% D-tagatose for 90 days, and the absence of adverse long-term consequences of glycogen-induced liver enlargement in rats, it is concluded that the observed liver enlargement in D-tagatose-fed rats has no relevance for the assessment of human safety of this substance. Copyright 1999

  9. Effect of perches on liver health of hens.

    Science.gov (United States)

    Jiang, S; Hester, P Y; Hu, J Y; Yan, F F; Dennis, R L; Cheng, H W

    2014-07-01

    Fatty liver is a common energy metabolic disorder in caged laying hens. Considering that the egg industry is shifting from conventional cages to alternative housing systems such as enriched cages, the objective of this study was to determine the effects of perches on fat deposition and liver health in laying hens. Three hundred twenty-four 17-wk-old White Leghorn hens were housed in 1 of 4 treatments with 9 hens per cage. Treatment 1 hens never had access to perches during their life cycle. Treatment 2 hens had access to perches during the pullet phase only. Treatment 3 hens had access to perches during the laying phase only. Treatment 4 hens always had access to perches. Liver weight, abdominal fat pad weight, BW, liver fat, and circulating alanine transaminase, aspartate transaminase, and adiponectin were determined. Provision of perches during either the rearing or laying phase did not affect liver health in 71-wk-old hens. However, perch access compared with no perch access during the egg laying phase reduced relative fat pad weight. These results suggest that providing perches as a means of stimulating activity reduced abdominal fat deposition in caged hens during the laying period. However, perch access in caged hens was ineffective in reducing fat deposition in the liver and altering enzyme activities related to improved liver function. © 2014 Poultry Science Association Inc.

  10. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    Directory of Open Access Journals (Sweden)

    Herxheimer Andrew

    2002-03-01

    Full Text Available Abstract Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis.

  11. Adrenal disorders and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Papanastasiou, Labrini; Fountoulakis, Stelios; Vatalas, Ioannis-Anastasios

    2017-06-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the developed world and its pathogenesis is complex and multifactorial. It is considered the hepatic manifestation of the metabolic syndrome and is the leading cause of hepatic cirrhosis. This review aims to present current knowledge on the involvement of the adrenal glands in the development of NAFLD. Clinical and animal studies have shown that excess glucocorticoids (GC) have been implicated in the pathogenesis of NAFLD. Patients with NAFLD seem to have a subtle chronic activation of the hypothalamic pituitary adrenal axis leading to a state of subclinical hypercortisolism. Regulators of GC such as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that regenerates cortisol from inactive cortisone, and 5α/5β-reductases, enzymes that increase cortisol clearance, are implicated in the development of NAFLD by amplifying local GC action. Adrenal androgen (dehydroepiandrosterone) abnormalities and increased aldosterone levels may also have a role in the development of NAFLD whereas the contribution of adrenergic signaling in NAFLD pathogenesis remains unclear.

  12. Effect of aspirin and prostaglandins on the carbohydrate metabolism in albino rats.: glucose oxidation through different pathways and glycolytic enzymes

    International Nuclear Information System (INIS)

    Balasubramanian, A.; Ramakrishnan, S.

    1980-01-01

    The effect of chronic and acute doses of aspirin and prostaglandins F2α and E2 individually on the oxidation of glucose through Embden Meyerhof-TCA cycle and pentose phosphate pathways and some key glycolytic enzymes of liver were studied in male albino rats. Studies were extended to find the combined effect of PGF2α and E2 with an acute dose of aspirin. There was increased utilisation of both 1- 14 C glucose and 6- 14 C glucose on aspirin treatment. However, the metabolism through the EM-TCA pathway was more pronounced as shown by a reduced ratio of 14 CO 2 from 1- 14 C and 6- 14 C glucose. Two hepatic key glycolytic enzymes viz. hexokinase and pyruvate kinase were increased due to aspirin treatment. Withdrawal of aspirin corrected the above impaired carbohydrate metabolism in liver. Prostaglandin F2α also caused a reduction in the utilisation of 1- 14 C glucose, while PGE2 recorded an increase in the utilisation of both 1- 14 C and 6- 14 C glucose when compared to controls, indicating that different members of prostaglandins could affect metabolisms and differently. Administration of the PGs and aspirin together showed an increase in the utilisation of 6- 14 C glucose. (auth.)

  13. Effects of dibutyl phthalate on lipid metabolism and drug metabolising enzyme system in rats

    International Nuclear Information System (INIS)

    Arakaki, Mitsuo; Ariyoshi, Toshihiko.

    1976-01-01

    Effects of dibutyl phthalate (DBP) on the liver constituents and the drug metabolizing enzyme system were investigated in rats. 1. In the experiments at a single oral dose of DBP (630 or 1260 mg/kg), the glycogen content was decreased only at the high dose, but no effects were observed on the contents of glycogen, triglyceride, microsomal protein and cytochromes, and on the activities of drug metabolizing enzymes. 2. In the repeated oral dose of DBP (630 or 1260 mg/kg/day) for 5 days, the ratio of liver weight to body weight was increased in both female and male rats, whereas the increases of cytochrome P-450 content and aniline hydroxylase activity were noted only in male rats. However, the contents of liver triglyceride, phospholipids, and cholesterol were unchanged. On the other hand, serum cholesterol content which showed the tendency to be decreased at the low dose was significantly decreased at the high dose. 3. In the incorporation of 1- 14 C-acetate into liver and serum lipids after repeated oral dose of DBP (630 mg/kg/day) for 5 days in male rats, the incorporation into triglyceride showed tendency to be increased, whereas the incorporation into cholesterol and cholesterol ester remained unchanged in vivo and in vitro. (auth.)

  14. Lipogenic potential of liver from morbidly obese patients with and without non-insulin-dependent diabetes

    International Nuclear Information System (INIS)

    Barakat, H.A.; McLendon, V.D.; Carpenter, J.W.; Marks, R.H.; Legett, N.; O'Brien, K.; Caro, J.F.

    1991-01-01

    Intra-abdominal liver biopsies were obtained during surgery from fasted obese patients with non-insulin-dependent diabetes mellitus (NIDDM), obese normoglycemic controls, and lean controls. Lipid synthesis was studied in freshly isolated hepatocytes and liver homogenates from the three groups of subjects. Incorporation of 3H2O into the lipids of hepatocytes was determined in the absence and presence of insulin (0.1 mumol/L). The activities of five enzymes involved in fatty acid synthesis, and the incorporation of 14C-glycerol-3-phosphate into lipids were determined in liver homogenates. Basal lipid synthesis by hepatocytes was not different in the three groups of patients. Insulin stimulated lipogenesis by 8% +/- 30% in the lean controls, 33% +/- 8% in the obese controls and 17% +/- 6% in the NIDDM patients. No significant differences in the activities of the five enzymes that are involved in de novo fatty acid synthesis among the three groups of patients were observed. Similarly, incorporation of 14C-glycerol-3-phosphate by liver homogenates, in the presence of saturating or submaximal concentrations of fatty acids, did not differ among the three groups. These results show that under the experimental conditions of this study, including the fasted state of the patients, the basal capacity of liver of NIDDM patients to synthesize fatty acids or glycerides is the same as that of liver from obese and lean controls. Thus, it is likely that an increase in fatty acid flux into a liver with normal lipogenic potential may contribute to the increased synthesis of triglycerides by the liver of these patients in vivo

  15. The effects of the continuous administration of N,N-dimethyl-4-phenylazoaniline (DAB) on the activities and the inducibilities of some drug-metabolizing enzymes in rat liver

    DEFF Research Database (Denmark)

    Autrup, Herman; Thurlow, Brenda J.; Warwick, Gerald P.

    1975-01-01

    of dye feeding on some of the enzyme activities in the two major liver lobes and differences were found. (3) The effect of phenobarbital (PB) pretreatment on the DAB-fed rats was studied at 4-week intervals. The activities of DAB-azoreductase and of nitroreductase increased throughout the whole period......-252-azoreductase was not induced by PB or MC, and CO did not inhibit its reduction. Its reduction depended only slightly on NADH. CO caused a greater relative decrease in the activity of DAB-azoreductase in dye-fed animals and also in animals following PB and MC pretreatment, implying a greater role of cytochrome...

  16. Bisphenol A sulfonation is impaired in metabolic and liver disease

    International Nuclear Information System (INIS)

    Yalcin, Emine B.; Kulkarni, Supriya R.; Slitt, Angela L.; King, Roberta

    2016-01-01

    Background: Bisphenol A (BPA) is a widely used industrial chemical and suspected endocrine disruptor to which humans are ubiquitously exposed. The liver metabolizes and facilitates BPA excretion through glucuronidation and sulfonation. The sulfotransferase enzymes contributing to BPA sulfonation (detected in human and rodents) is poorly understood. Objectives: To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers. Methods: The capacity for BPA sulfonation was determined in human liver samples that were categorized into different stages of metabolic and liver disease (including obesity, diabetes, steatosis, and cirrhosis) and in livers from ob/ob mice. Results: In human liver tissues, BPA sulfonation was substantially lower in livers from subjects with steatosis (23%), diabetes cirrhosis (16%), and cirrhosis (18%), relative to healthy individuals with non-fatty livers (100%). In livers of obese mice (ob/ob), BPA sulfonation was lower (23%) than in livers from lean wild-type controls (100%). In addition to BPA sulfonation activity, Sult1a1 protein expression decreased by 97% in obese mouse livers. Conclusion: Taken together these findings establish a profoundly reduced capacity of BPA elimination via sulfonation in obese or diabetic individuals and in those with fatty or cirrhotic livers versus individuals with healthy livers. - Highlights: • Present study demonstrates that hepatic SULT 1A1/1A3 are primarily sulfonate BPA in mouse and human. • Hepatic BPA sulfonation is profoundly reduced steatosis, diabetes and cirrhosis. • With BPA-S detectable in urine under low or common exposures, these findings are novel and important.

  17. Bisphenol A sulfonation is impaired in metabolic and liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Yalcin, Emine B.; Kulkarni, Supriya R.; Slitt, Angela L., E-mail: angela_slitt@uri.edu; King, Roberta, E-mail: rking@uri.edu

    2016-02-01

    Background: Bisphenol A (BPA) is a widely used industrial chemical and suspected endocrine disruptor to which humans are ubiquitously exposed. The liver metabolizes and facilitates BPA excretion through glucuronidation and sulfonation. The sulfotransferase enzymes contributing to BPA sulfonation (detected in human and rodents) is poorly understood. Objectives: To determine the impact of metabolic and liver disease on BPA sulfonation in human and mouse livers. Methods: The capacity for BPA sulfonation was determined in human liver samples that were categorized into different stages of metabolic and liver disease (including obesity, diabetes, steatosis, and cirrhosis) and in livers from ob/ob mice. Results: In human liver tissues, BPA sulfonation was substantially lower in livers from subjects with steatosis (23%), diabetes cirrhosis (16%), and cirrhosis (18%), relative to healthy individuals with non-fatty livers (100%). In livers of obese mice (ob/ob), BPA sulfonation was lower (23%) than in livers from lean wild-type controls (100%). In addition to BPA sulfonation activity, Sult1a1 protein expression decreased by 97% in obese mouse livers. Conclusion: Taken together these findings establish a profoundly reduced capacity of BPA elimination via sulfonation in obese or diabetic individuals and in those with fatty or cirrhotic livers versus individuals with healthy livers. - Highlights: • Present study demonstrates that hepatic SULT 1A1/1A3 are primarily sulfonate BPA in mouse and human. • Hepatic BPA sulfonation is profoundly reduced steatosis, diabetes and cirrhosis. • With BPA-S detectable in urine under low or common exposures, these findings are novel and important.

  18. [Non-invasive assessment of fatty liver].

    Science.gov (United States)

    Egresi, Anna; Lengyel, Gabriella; Hagymási, Krisztina

    2015-04-05

    As the result of various harmful effects (infectious agents, metabolic diseases, unhealthy diet, obesity, toxic agents, autoimmune processes) hepatic damage may develop, which can progress towards liver steatosis, and fibrosis as well. The most common etiological factors of liver damages are hepatitis B and C infection, alcohol consumption and non-alcoholic fatty liver disease. Liver biopsy is considered as the gold standard for the diagnosis of chronic liver diseases. Due to the dangers and complications of liver biopsy, studies are focused on non-invasive markers and radiological imaging for liver steatosis, progression of fatty liver, activity of the necroinflammation and the severity of the fibrosis. Authors review the possibilities of non-invasive assessment of liver steatosis. The statistical features of the probes (positive, negative predictive values, sensitivity, specificity) are reviewed. The role of radiological imaging is also discussed. Although the non-invasive methods discussed in this article are useful to assess liver steatosis, further studies are needed to validate to follow progression of the diseases and to control therapeutic response.

  19. Drug-induced liver injury due to antimicrobials, central nervous system agents, and nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Devarbhavi, Harshad; Andrade, Raúl J

    2014-05-01

    Antimicrobial agents including antituberculosis (anti-TB) agents are the most common cause of idiosyncratic drug-induced liver injury (DILI) and drug-induced liver failure across the world. Better molecular and genetic biomarkers are acutely needed to help identify those at risk of liver injury particularly for those needing antituberculosis therapy. Some antibiotics such as amoxicillin-clavulanate and isoniazid consistently top the lists of agents in retrospective and prospective DILI databases. Central nervous system agents, particularly antiepileptics, account for the second most common class of agents implicated in DILI registries. Hepatotoxicity from older antiepileptics such as carbamazepine, phenytoin, and phenobarbital are often associated with hypersensitivity features, whereas newer antiepileptic drugs have a more favorable safety profile. Antidepressants and nonsteroidal anti-inflammatory drugs carry very low risk of significant liver injury, but their prolific use make them important causes of DILI. Early diagnosis and withdrawal of the offending agent remain the mainstays of minimizing hepatotoxicity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  20. The effect of rutin on lipid profile and liver function enzymes on ...

    African Journals Online (AJOL)

    pc

    2017-06-01

    Jun 1, 2017 ... However, there was a significant (p<0.05) inc compared to diabetic control. Furthermore, serum liver .... orange, grapefruit, lemon and lime) and apple; berries such as mulberry, ash tree fruits and ... Glibenclamide and alloxan were purchased from. Sigma chemical Company St. Louis U.S.A. Rutin was.

  1. Computational Modeling in Liver Surgery

    Directory of Open Access Journals (Sweden)

    Bruno Christ

    2017-11-01

    Full Text Available The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant. However, size and function of the liver are not necessarily equivalent. Hence, determining the future liver volume might misestimate the future liver function, especially in cases of hepatic comorbidities such as hepatic steatosis. A systems medicine approach could be applied, including biological, medical, and surgical aspects, by integrating all available anatomical and functional information of the individual patient. Such an approach holds promise for better prediction of postoperative liver function and hence improved risk assessment. This review provides an overview of mathematical models related to the liver and its function and explores their potential relevance for computational liver surgery. We first summarize key facts of hepatic anatomy, physiology, and pathology relevant for hepatic surgery, followed by a description of the computational tools currently used in liver surgical planning. Then we present selected state-of-the-art computational liver models potentially useful to support liver surgery. Finally, we discuss the main challenges that will need to be addressed when developing advanced computational planning tools in the context of liver surgery.

  2. Cloning and characterization of human liver cytosolic beta-glycosidase

    NARCIS (Netherlands)

    De Graaf, M; Van Veen, IC; Van Der Meulen-Muileman, IH; Gerritsen, WR; Pinedo, HM; Haisma, HJ

    2001-01-01

    Cytosolic beta -glucosidase (EC 3.2.1.21) from mammalian liver is a member of the family 1 glycoside hydrolases and is known for its ability to hydrolyse a range of beta -D-glycosides. including beta -D-glucoside acid beta -D-galactoside. We therefore refer to this enzyme as cytosolic beta

  3. Developmental changes in rat liver branched-chain 2-oxo acid dehydrogenase.

    OpenAIRE

    May, E E; May, M E; Aftring, R P; Buse, M G

    1982-01-01

    Branched-chain 2-oxo acid dehydrogenase catalyses the first irreversible step in the degradation of the branched-chain amino acids leucine, isoleucine and valine. With specifically labelled 4-methyl-2-oxo[1-14C]pentanoate as substrate, the enzyme's activity was measured in rat liver homogenates. Activity (per g wet wL of liver or per mg of protein) increased most rapidly during the perinatal period (2 days before to 1 day after birth), reaching approximately adult values by the time of weanin...

  4. [L-arginine metabolism enzyme activities in rat liver subcellular fractions under condition of protein deprivation].

    Science.gov (United States)

    Kopyl'chuk, G P; Buchkovskaia, I M

    2014-01-01

    The features of arginase and NO-synthase pathways of arginine's metabolism have been studied in rat liver subcellular fractions under condition of protein deprivation. During the experimental period (28 days) albino male rats were kept on semi synthetic casein diet AIN-93. The protein deprivation conditions were designed as total absence of protein in the diet and consumption of the diet partially deprived with 1/2 of the casein amount compared to in the regular diet. Daily diet consumption was regulated according to the pair feeding approach. It has been shown that the changes of enzyme activities, involved in L-arginine metabolism, were characterized by 1.4-1.7 fold decrease in arginase activity, accompanied with unchanged NO-synthase activity in cytosol. In mitochondrial fraction the unchanged arginase activity was accompanied by 3-5 fold increase of NO-synthase activity. At the terminal stages of the experiment the monodirectional dynamics in the studied activities have been observed in the mitochondrial and cytosolfractions in both experimental groups. In the studied subcellular fractions arginase activity decreased (2.4-2.7 fold with no protein in the diet and 1.5 fold with partly supplied protein) and was accompanied by NO-synthase activity increase by 3.8 fold in cytosole fraction, by 7.2 fold in mitochondrial fraction in the group with no protein in the diet and by 2.2 and 3.5 fold in the group partialy supplied with protein respectively. The observed tendency is presumably caused by the switch of L-arginine metabolism from arginase into oxidizing NO-synthase parthway.

  5. Posttraumatic venous gas in the liver - a case report and review of the current literature.

    Science.gov (United States)

    Fahrner, René; Rauchfuss, Falk; Scheuerlein, Hubert; Settmacher, Utz

    2018-03-02

    There are numerous causes of hepatic gas formation that range from serious pathologies to incidental findings, including mesenteric infarction, liver abscess, inflammatory bowel disease or minimally invasive hepatic interventions. We report a case of a 50-year-old man who was admitted to the emergency room after a car accident. The clinical examination and further diagnostics revealed a craniocerebral injury with a fracture of the skull, concomitant soft tissue lesions and subarachnoidal bleeding. Furthermore, a blunt thoracic trauma with hemopneumothorax due to rib fractures was treated with a chest tube. No obvious abdominal pathology was seen. While in the operating theatre for the surgical revision of the cranial soft tissue lesions, a femoral venous catheter was inserted without any complications. A routine ultrasound of the abdomen six hours after the trauma revealed unclear hepatic gas formation. A contrast-enhanced computer tomography (CT) scan of the abdomen was performed, and the gas formation was found to be localized within the left hepatic vein. Afterwards, there was no specific treatment of the hepatic venous gas formation, as no alterations of liver function or liver enzymes were seen. The further course of the patient was uneventful regarding the gas formation in the liver, and another ultrasound two days later revealed no further gas in the liver. The placement of a femoral venous catheter is a risk factor for gas formation in liver veins. No further treatment is needed in cases with stable liver function. To rule out serious pathologies, diagnostic findings (e.g., ultrasound, CT), clinical history and underlying diseases need to be analyzed carefully after the detection of intrahepatic gas formation. With contrast-enhanced CT, the localization of the gas and its potential causes might be detectable.

  6. Paracetamol overdose: the liver unit perspective.

    LENUS (Irish Health Repository)

    Iqbal, M

    2012-09-01

    Liver failure resulting from deliberate or accidental paracetamol overdose continues to be an important reason for referral to liver transplant centres. Severe hepatic dysfunction often appears 72-96 h after overdose. Liver injury can be prevented by timely administration of the specific antidote, N-acetylcysteine. Unfortunately, administration of N-acetylcysteine is frequently delayed due to late presentation or late administration. While N-acetylcysteine works best if given within 8 h of overdose, it is beneficial at any time period and should always be given if there is concern about significant overdose, irrespective of interval from time of ingestion. Early discussion with liver transplant unit is suggested if there is any doubt or evidence of liver failure.

  7. Pharmacogenetic effects of angiotensin-converting enzyme inhibitors over age-related urea andcreatinine variations in patients with dementia due to Alzheimer disease

    OpenAIRE

    Ferreira de Oliveira, Fabricio; Berretta, Juliana Marília; Suchi Chen, Elizabeth; Cardoso Smith, Marilia; Ferreira Bertolucci, Paulo Henrique

    2016-01-01

    Background: Renal function declines according to age and vascular risk factors, whereas few data are available regarding geneticallymediated effects of anti-hypertensives over renal function. Objective: To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis). Methods: Consecutive outpatients older than 60 years-old with AD and no history of kid...

  8. Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure

    NARCIS (Netherlands)

    Lisman, T.; Bakhtiari, K.; Adelmeijer, J.; Meijers, J. C. M.; Porte, R. J.; Stravitz, R. T.

    2012-01-01

    . Background: It has been well established that hemostatic potential in patients with chronic liver disease is in a rebalanced status due to a concomitant decrease in pro- and antihemostatic drivers. The hemostatic changes in patients with acute liver injury/failure (ALI/ALF) are similar but not

  9. Intact thrombin generation and decreased fibrinolytic capacity in patients with acute liver injury or acute liver failure

    NARCIS (Netherlands)

    Lisman, T.; Bakhtiari, K.; Adelmeijer, J.; Meijers, J. C. M.; Porte, R. J.; Stravitz, R. T.

    . Background: It has been well established that hemostatic potential in patients with chronic liver disease is in a rebalanced status due to a concomitant decrease in pro- and antihemostatic drivers. The hemostatic changes in patients with acute liver injury/failure (ALI/ALF) are similar but not

  10. Chitosan nanoparticles from marine squid protect liver cells against N-diethylnitrosoamine-induced hepatocellular carcinoma.

    Science.gov (United States)

    Subhapradha, Namasivayam; Shanmugam, Vairamani; Shanmugam, Annaian

    2017-09-01

    Rationale of this study was framed to investigate the protective effect and anti-cancer property of nanoparticles based on chitosan isolated from squid, Sepioteuthis lessoniana, on hepatic cells in N-Nitrosodiethylamine-induced hepatocellular carcinoma in rats. The results conferred that the chitosan nanoparticle supplementation had a protective effect on liver cells by reducing the levels of marker enzymes and bilirubin and thus increasing the albumin levels. The level of reduced glutathione, ascorbic acid and α-tocopherol significantly increased in both post- and pre-treatment with chitosan nanoparticles. The levels of antioxidant enzymes were enhanced and lipid peroxidation products were diminished while treating nitrosodiethylamine-induced hepatocellular carcinoma with chitosan nanoparticles. Supplementation of chitosan nanoparticles had potent anti-hyperlipidemic property that was evidenced by monitoring the serum lipid levels and its components. Animals pre-treated with chitosan nanoparticles along with nitrosodiethylamine showed a significant reduction in the total cholesterol and triglycerides levels with increase in the levels of phospholipids and free fatty acids. Chitosan nanoparticles treated rats showed significant increment in high-density lipoprotein cholesterol and reduction in low-density lipoprotein and very low-density lipoprotein cholesterol when compared with levels in nitrosodiethylamine-induced hepatocellular carcinoma. Nitrosodiethylamine-induced carcinoma changes on circulation and hepatic antioxidant defense mechanism were regulated by chitosan nanoparticles, concluding that the chitosan nanoparticles have a potent protective effect on liver cells which might be due to its robust antioxidant and anti-lipidemic property. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Endocrine causes of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Marino, Laura; Jornayvaz, François R

    2015-10-21

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed.

  12. A brain-liver circuit regulates glucose homeostasis.

    Science.gov (United States)

    Pocai, Alessandro; Obici, Silvana; Schwartz, Gary J; Rossetti, Luciano

    2005-01-01

    Increased glucose production (GP) is the major determinant of fasting hyperglycemia in diabetes mellitus. Previous studies suggested that lipid metabolism within specific hypothalamic nuclei is a biochemical sensor for nutrient availability that exerts negative feedback on GP. Here we show that central inhibition of fat oxidation leads to selective activation of brainstem neurons within the nucleus of the solitary tract and the dorsal motor nucleus of the vagus and markedly decreases liver gluconeogenesis, expression of gluconeogenic enzymes, and GP. These effects require central activation of ATP-dependent potassium channels (K(ATP)) and descending fibers within the hepatic branch of the vagus nerve. Thus, hypothalamic lipid sensing potently modulates glucose metabolism via neural circuitry that requires the activation of K(ATP) and selective brainstem neurons and intact vagal input to the liver. This crosstalk between brain and liver couples central nutrient sensing to peripheral nutrient production and its disruption may lead to hyperglycemia.

  13. Heterogeneous expression of cholesterol 7α-hydroxylase and sterol 27- hydroxylase genes in the rat liver lobulus

    NARCIS (Netherlands)

    Twisk, J.; Hoekman, M.F.M.; Mager, W.H.; Moorman, A.F.M.; Boer, P.A.J. de; Scheja, L.; Princen, H.M.G.; Gebhardt, R.

    1995-01-01

    We investigated the lobular localization and molecular level of expression of cholesterol 7α-hydroxylase and sterol 27-hydroxylase, two key enzymes in bile acid synthesis, in isolated periportal and pericentral hepatocytes and by in situ hybridization of rat liver. Enzyme activity, mRNA, and gene

  14. Hemostatic mechanism underlying microbubble-enhanced non-focused ultrasound in the treatment of a rabbit liver trauma model

    Science.gov (United States)

    Zhao, Da-wei; Tian, Meng; Yang, Jian-zheng; Du, Peng; Bi, Jie; Zhu, Xinjian

    2016-01-01

    The aim of our study was to investigate the hemostatic mechanism underlying microbubble-enhanced non-focused ultrasound treatment of liver trauma. Thirty rabbits with liver trauma were randomly divided into three groups—the microbubble-enhanced ultrasound (MEUS; further subdivided based on exposure intensity into MEUS1 [0.11 W/cm2], MEUS2 [0.55 W/cm2], and MEUS3 [1.1 W/cm2]), ultrasound without microbubbles (US), and microbubbles without ultrasound (MB) groups. The pre- and post-treatment bleeding weight and visual bleeding scores were evaluated. The serum liver enzyme concentrations as well as the blood perfusion level represented by mean peak contrast intensity (PI) ratio in the treatment area were analyzed. The hemostatic mechanism was evaluated by histological and transmission electron microscopic examination of liver tissue samples. The MEUS subgroups 1–3 (grade 0–1, grade 0–2, and grade 1–2, respectively) exhibited significantly lower post-treatment visual bleeding scores than the US and MB groups (both, grade 3–4; all, P hepatic cells became edematous and compressed the hepatic sinus and associated blood vessels. However, the serum liver enzyme levels were not significantly altered. Microbubble-enhanced non-focused ultrasound does not significantly affect blood perfusion and liver function and can be used to induce rapid hemostasis in case of liver trauma. PMID:27633577

  15. Activity of peroxisomal enzymes and intracellular distribution of catalase in Zellweger syndrome

    NARCIS (Netherlands)

    Schrakamp, G.; Bosch, H. van den; Roest, B.; Kos, M.; Meijer, A.J.; Heymans, H.S.A.; Tegelaers, W.H.H.; Schutgens, R.B.H.; Tager, J.M.; Wanders, R.J.A.

    1984-01-01

    The activity of peroxisomal enzymes was studied in human liver and cultured human skin fibroblasts in relation to the finding (Goldfischer, S. et al. (1973) Science 182, 62–64) that morphologically distinct peroxisomes are not detectable in patients with the cerebro-hepato-renal (Zellweger)

  16. Activity of peroxisomal enzymes and intracellular distribution of catalase in Zellweger syndrome

    NARCIS (Netherlands)

    Wanders, R. J.; Kos, M.; Roest, B.; Meijer, A. J.; Schrakamp, G.; Heymans, H. S.; Tegelaers, W. H.; van den Bosch, H.; Schutgens, R. B.; Tager, J. M.

    1984-01-01

    The activity of peroxisomal enzymes was studied in human liver and cultured human skin fibroblasts in relation to the finding (Goldfischer, S. et al. (1973) Science 182, 62-64) that morphologically distinct peroxisomes are not detectable in patients with the cerebro-hepato-renal (Zellweger)

  17. An epidemiological study of the association of coffee with chronic liver disease.

    Science.gov (United States)

    Walton, H B; Masterton, G S; Hayes, P C

    2013-11-01

    Chronic liver disease affects 855 people per million in the UK. Previous studies have reported that coffee appears protective against the development of abnormal liver enzymes, hepatic fibrosis and cirrhosis. The aim of this study, the first in a Scottish population, was to compare coffee consumption in patients with liver disease and that of control populations to determine correlations between coffee intake and the incidence of non-cancerous liver disease and with Child's-Pugh and model for end-stage liver disease (MELD) scores. Two hundred and eighty-six patients attending the liver outpatient department at the Royal Infirmary of Edinburgh completed a questionnaire regarding coffee consumption and lifestyle factors. Control questionnaires were also completed by 100 orthopaedic outpatients and 120 medical students. Patients with cirrhosis (n = 95) drank significantly less coffee than those without cirrhosis (p = coffee consumption. Coffee drinking is associated with a reduced prevalence of cirrhosis in patients with chronic liver disease. However, there was no significant difference in the amount of coffee drunk by liver patients and the control groups. It is possible that by changing the amount of coffee drunk, the development of cirrhosis in liver disease could be postponed.

  18. Monkey liver cytochrome P450 2C9 is involved in caffeine 7-N-demethylation to form theophylline.

    Science.gov (United States)

    Utoh, Masahiro; Murayama, Norie; Uno, Yasuhiro; Onose, Yui; Hosaka, Shinya; Fujino, Hideki; Shimizu, Makiko; Iwasaki, Kazuhide; Yamazaki, Hiroshi

    2013-12-01

    Caffeine (1,3,7-trimethylxanthine) is a phenotyping substrate for human cytochrome P450 1A2. 3-N-Demethylation of caffeine is the main human metabolic pathway, whereas monkeys extensively mediate the 7-N-demethylation of caffeine to form pharmacological active theophylline. Roles of monkey P450 enzymes in theophylline formation from caffeine were investigated using individual monkey liver microsomes and 14 recombinantly expressed monkey P450 enzymes, and the results were compared with those for human P450 enzymes. Caffeine 7-N-demethylation activity in microsomes from 20 monkey livers was not strongly inhibited by α-naphthoflavone, quinidine or ketoconazole, and was roughly correlated with diclofenac 4'-hydroxylation activities. Monkey P450 2C9 had the highest activity for caffeine 7-N-demethylation. Kinetic analysis revealed that monkey P450 2C9 had a high Vmax/Km value for caffeine 7-N-demethylation, comparable to low Km value for monkey liver microsomes. Caffeine could dock favorably with monkey P450 2C9 modeled for 7-N-demethylation and with human P450 1A2 for 3-N-demethylation. The primary metabolite theophylline was oxidized to 8-hydroxytheophylline in similar ways by liver microsomes and by recombinant P450s in both humans and monkeys. These results collectively suggest a high activity for monkey liver P450 2C9 toward caffeine 7-N-demethylation, whereas, in humans, P450 1A2-mediated caffeine 3-N-demethylation is dominant.

  19. Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

    Science.gov (United States)

    Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

    2016-09-01

    Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. The dogfish shark (Squalus acanthias) increases both hepatic and extrahepatic ornithine urea cycle enzyme activities for nitrogen conservation after feeding.

    Science.gov (United States)

    Kajimura, Makiko; Walsh, Patrick J; Mommsen, Thomas P; Wood, Chris M

    2006-01-01

    Urea not only is utilized as a major osmolyte in marine elasmobranchs but also constitutes their main nitrogenous waste. This study investigated the effect of feeding, and thus elevated nitrogen intake, on nitrogen metabolism in the Pacific spiny dogfish Squalus acanthias. We determined the activities of ornithine urea cycle (O-UC) and related enzymes in liver and nonhepatic tissues. Carbamoyl phosphate synthetase III (the rate-limiting enzyme of the O-UC) activity in muscle is high compared with liver, and the activities in both tissues increased after feeding. The contribution of muscle to urea synthesis in the dogfish body appears to be much larger than that of liver when body mass is considered. Furthermore, enhanced activities of the O-UC and related enzymes (glutamine synthetase, ornithine transcarbamoylase, arginase) were seen after feeding in both liver and muscle and were accompanied by delayed increases in plasma urea, trimethylamine oxide, total free amino acids, alanine, and chloride concentrations, as well as in total osmolality. The O-UC and related enzymes also occurred in the intestine but showed little change after feeding. Feeding did not change the rate of urea excretion, indicating strong N retention after feeding. Ammonia excretion, which constituted only a small percentage of total N excretion, was raised in fed fish, while plasma ammonia did not change, suggesting that excess ammonia in plasma is quickly ushered into synthesis of urea or protein. In conclusion, we suggest that N conservation is a high priority in this elasmobranch and that feeding promotes ureogenesis and growth. Furthermore, exogenous nitrogen from food is converted into urea not only by the liver but also by the muscle and to a small extent by the intestine.