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Effects of vanadate and insulin on the activities of selected enzymes of amino acid metabolism in alloxan diabetic rat kidney.

The effects of insulin and the insulin mimetic agent "vanadate" were studied on the activities of alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase and arginase in the cytosolic and the mitochondrial fractions of the kidney in control and alloxan induced diabetic rats. An enhancement in the activities of these enzymes were noted in both the fractions of diabetic kidney. Vanadate treatment (0.6 mg/ml in drinking water) of alloxan induced diabetic rats restored the activities of these enzymes almost completely in the cytosolic and partially in the mitochondrial fractions. Vanadate treatment also normalized hyperglycaemia without altering the depressed levels of insulin secretion in diabetic rats. The effect of insulin treatment was found to be the same as that of vanadate in diabetic rats.

Alanine Transaminase↗

Toxic and sub-lethal effects of oleandrin on biochemical parameters of fresh water air breathing murrel, Channa punctatus (Bloch.).

Active compound oleandrin extracted from Nerium indicum (Lal Kaner) leaf has potent piscicidal activity. The piscicidal activity of oleandrin on freshwater fish C. punctatus was both time and dose dependent. Exposure to sub-lethal doses of oleandrin for 24hr and 96hr to fish caused significant alteration in the level of total protein, total free amino acid, nucleic acid, glycogen, pyruvate, lactate and enzyme protease, phosphatases, alanine aminotransferase, aspartate aminotransferase and acetylcholinesterase activity in liver and muscle tissues. The alterations in all the above biochemical parameters were also significantly time and dose dependent. The results show a significant recovery in all the above biochemical parameters, in both liver and muscle tissues of fish after the 7th day of the withdrawal of treatment. Toxicity persistence test of oleandrin on juvenile Labeo rohita shows that fish seed of common culturing carp can be released into rearing ponds after three days of oleandrin treatment. It supports the view that the oleandrin is safer and may be useful substitute of other piscicides for removing the unwanted freshwater fishes from aquaculture ponds.

Acetylcholinesterase↗

Organism reaction to cryodestruction of the prostatic gland in dogs.

The aim of the investigation was to determine the effect of cryodestruction of the healthy prostate on general condition of dogs. The research was performed on 18 dogs divided into two groups: control and experimental. In the dogs from the experimental group after the laparotomy procedure the prostate was frozen in the repeated cycle using the flat cryoapplicator. The observations were carried out for 6 months. General condition of dogs was controlled, blood was examined and urine analysed. The performed determinations included the activity of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, acid phosphatase and prostatic isoenzyme of acid phosphatase. It has been observed that the cryodestruction procedures of the prostatic gland are well tolerated by dogs. During 3 weeks after the surgery the number of leucocytes in blood increased. An increased drop of the blood cells was observed for 2 weeks after the procedure. Characteristic behaviour was observed in case of the prostatic isoenzyme of acid phosphatase. Immediately after the procedure the increased activity of that enzyme was observed and 24h later its decrease which remained for about 2 weeks. Then the isoenzyme activity increased again and that increase lasted for the period of 2 months.

Acid Phosphatase↗

Stability and storage characteristics of enzymes in cattle blood.

The stability and storage characteristics were studied of 11 bovine enzymes of potential clinical significance, namely, aldolase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, acetylcholinesterase, creatine kinase, gamma glutamyltransferase, glutathione peroxidase (GSH-Px), alpha-hydroxybutyrate dehydrogenase, lactate dehydrogenase and superoxide dismutase (SOD). Enzyme activities in fresh serum were compared with those in plasma containing various anticoagulants including lithium heparin, EDTA and oxalate/fluoride. The same preservatives were assessed for their effects on the whole blood activities of GSH-Px and SOD. Stabilities of enzymes in plasma and serum stored at room (+20 degrees C), refrigerator (4 degrees C) or deep freeze (-20 degrees C) temperatures were also compared. In addition, SOD and GSH-Px activities in samples stored, at the same temperatures, as whole blood or aqueous lysates were monitored.

Acetylcholinesterase↗

[Effects of esmolol- and sodium nitroprusside-induced controlled hypotension on hepatocellular integrity in patients undergoing endonasal sinus surgery].

BACKGROUND: Controlled hypotension (CH) is an established method to reduce intraoperative bleeding. The aim of the study was to investigate the influence of CH induced by sodium nitroprusside (SN) or esmolol on hepatocellular integrity. METHODS: Prospective, randomized, controlled study. 45 patients scheduled for elective endonasal sinus surgery were allocated to one of the following three groups: 1. SN-group (n = 15): CH induced by SN. 2. Esmolol-group: CH induced by esmolol. In both groups mean arterial pressure was kept between 50-55 mmHg. 3. Control group (n = 15): no hypotension was performed (MAP > 70 mmHg). The cytosolic liver enzyme alpha-glutathione S-transferase (alpha-GST) and standard liver enzymes (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase) were measured at the following timepoints: preoperative (T0), at the end of surgery (T1), 2 h (T2), 24 h (T3) and 48 h (T4) postoperatively. RESULTS: alpha-GST concentrations were significantly higher in patients receiving CH (SN: 5.9 +/- 3.4; Esmolol: 6.5 +/- 2.8 microg/L) in comparison with controls (2.5 +/- 1.4 microg/L) at T1. Already at T2 there were no significant differences between the three groups. Standard liver enzymes showed a similar course in all groups. CONCLUSION: The small but significant increase of alpha-GST in both hypotension groups suggests that hypotension induces a mild damage of hepatocellular integrity.

Adrenergic beta-Antagonists↗

Effects of ursodeoxycholic acid (ursodiol) treatment on chronic viral hepatitis in heart transplant patients: results of a prospective, double-blind, placebo-randomized study.

BACKGROUND: Chronic viral hepatitis averages 15% to 20% in heart transplant patients. Several studies have shown that ursodiol may improve liver biochemistry in patients with chronic hepatitis. We used a double-blind randomized controlled trial to evaluate the effect of ursodiol in heart transplant patients with chronic viral hepatitis. METHODS: Thirty heart patients with chronic viral hepatitis B, C, or non-A-G received ursodiol, 800 mg per day (group 1), and 30 received placebo (group 2) for 12 months. Endpoints were improvement in liver biochemical tests and in total Knodell score. Intent-to-treat and per-protocol analyses were performed. RESULTS: At entry, both groups were comparable for all of the studied parameters. During the study period, serum alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase variations were not different between group 1 and group 2 patients. Knodell score improved in 20% of group 1 patients and in 43% of group 2 patients (NS). Adverse events or mortality were not different in the two groups during the study period. Similar results were observed by intent-to-treat and per-protocol analyses. CONCLUSIONS: A 12-month course of ursodiol therapy had no effect on liver enzymes or liver histology in heart transplant patients with chronic hepatitis.

Adult↗

Antiapoptotic and protective effects of roscovitine on ischemia-reperfusion injury of the rat liver.

OBJECTIVE: This study was designed to investigate the role of apoptosis on liver IR injury and to determine the effects of roscovitine on this process. MATERIALS AND METHODS: Rat livers pretreated with roscovitine received 60 min right lobe ischemia followed by 4 h (n=8) and 24 h (n=8) reperfusion. Tissue injury was evaluated by serum alanine aminotransferase, aspartate aminotransferase, tissue malondialdehyde, myeloperoxidase measurements and histological examination. Dead (apoptotic and necrotic) hepatocytes were determined by trypan blue dye and apoptosis was evaluated with M30 monoclonal antibody. RESULTS: Administration of roscovitine significantly decreased both apoptotic and dead hepatocyte counts compared to controls (P<0.01). Liver transaminase levels were decreased significantly in the roscovitine-pretreated groups (P<0.05). In the groups evaluated 24 h after reperfusion, MPO levels (P<0.02) and leukocyte infiltration on histologic sections were decreased significantly in the roscovitine-administered group compared to its control. CONCLUSIONS: This study indicates that hepatocyte apoptosis may play a role in the development of IR injury of the liver. Administration of roscovitine may be beneficial in preventing this injury.

Alanine Transaminase↗

NOAEL and LOAEL determinations of acute hepatotoxicity for chloroform and bromodichloromethane delivered in an aqueous vehicle to F344 rats.

Chloroform (CHCl3) and bromodichloromethane (BDCM) are generally the two most prevalent disinfection by-products formed during chlorination of drinking water, and both have been shown to be hepatotoxic, nephrotoxic, and carcinogenic in rodents. As the toxicity of these trihalomethanes (THMs) has most often been studied with corn oil as the vehicle of administration, the objectives of this study were to assess hepatotoxicity after exposure to single, low dosages of CHCl3 and BDCM given orally in an aqueous vehicle to estimate a lowest-observed-adverse-effect level (LOAEL) and a no-observed-adverse-effect level (NOAEL) and to compare toxic potency. Ninety-day-old male Fischer 344 rats were gavaged with either 0.125, 0.1875, 0.25, 0.5, 0.75, 1.0, or 1.5 mmol CHCl3 or BDCM/kg body weight in 10% Alkamuls EL-620 (5 ml/kg body weight). At 24 h postgavage, serum was collected for analysis of clinical chemistry indicators of liver damage. Both CHCl3 and BDCM induced dose-dependent hepatotoxicity; serum alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase were elevated significantly over control at 1.5, 1.0, and 0.5 mmol/kg. At these dose levels after 24 h, the two THMs appeared to be equipotent hepatotoxicants. Additional assessments at later time points demonstrated that BDCM causes more persistent liver damage than CHCl3 (Lilly et al., 1997). At 0.25, 0. 1875, and 0. 125 mmol of either THM/kg, significant increases over control were not detected for any measured endpoint. Therefore, these data indicate that the acute, oral NOAELs and LOAELs for liver toxicity are 0.25 and 0.5 mmol/kg, respectively, for both CHCl3 and BDCM. These determinations should provide a basis to establish new exposure limits for One-Day Health Advisories for these prevalent THMs.

Alanine Transaminase↗

Stability and storage characteristics of enzymes in sheep blood.

The stability and storage characteristics were studied of 11 ovine enzymes of potential clinical significance, namely, aldolase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, acetylcholinesterase, creatine kinase, gamma glutamyltransferase, glutathione peroxidase (GSH-Px), alpha-hydroxybutyrate dehydrogenase, lactate dehydrogenase and superoxide dismutase (SOD). Enzyme activities in fresh serum were compared with those in plasma containing various anticoagulants including lithium heparin, EDTA and oxalate/fluoride. The same preservatives were assessed for their effects on the whole blood activities of GSH-Px and SOD. Stabilities of enzymes in plasma and serum stored at room (+20 degrees C), refrigerator (4 degrees C) or deep freeze (-20 degrees C) temperatures were also compared. In addition, SOD and GSH-Px activities in samples stored, at the same temperatures, as whole blood or aqueous lysates were monitored. The results are discussed with particular reference to the differences between sheep and cattle.

Acetylcholinesterase↗

Sequential clinical, haematological, biochemical, immunopathological and histopathological alterations in buffalo calves (Bubalus bubalis) intravenously infected with Absidia corymbifera.

Absidiosis was produced experimentally in 18 buffalo calves by intravenous inoculation of spores of Absidia corymbifera. Infected animals exhibited dullness, depression, partial anorexia and an initial pyrexia and coughing during the first week and two animals died on each of 9, 13 and 16 days post infection (DPI). The haemoglobin concentration and total erythrocyte count showed no appreciable change from their basal values at any stage of the experiment. However, the erythrocyte sedimentation rate and total leukocyte count increased significantly in the infected animals. The differential leukocyte count revealed a relative neutrophilia from 5 to 20 DPI. There was a significant increase in the serum total proteins, blood urea nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, serum alkaline phosphatase, total immunoglobulins and circulating immune complexes in the infected animals as compared to the controls. In the sera of the infected animals, specific Absidia corymbifera IgM and IgG antibodies were detected from 3 DPI to 6 DPI respectively by Dot-EIA. Type I and type III skin hypersensitivity were detected from 10 DPI and type IV hypersensitivity from 15 DPI onwards. The gross and microscopic pathological lesions were seen mainly in the lungs, in all except one of the affected animals. This animal died 9 DPI and mycotic granulomas were also seen in its heart and kidneys. The microscopic lesions in the lung took the form of well-developed granulomas.

Absidia↗

Review of exertional rhabdomyolysis and a case in a rhesus monkey (Macaca mulatta).

This is the first confirmed report of exertional rhabdomyolysis in a non-human primate. The monkey was singly housed and presented with anorexia and reluctance to move. There was no external evidence of trauma. Clinicopathologic findings included mild azotemia, marked elevation in serum creatine phosphokinase (CPK), alanine aminotransferase, aspartate aminotransferase, and myoglobinuria. Two days post-incident, the peripheral skeletal muscle had marked multifocal myonecrosis and fibrillar disruption without an inflammatory reaction. Treatment included diuresis and pain relief, and urinary output was monitored. The monkey recovered over the next two weeks. The major significance of skeletal muscle damage is the potential of released myoglobin to cause acute renal failure in the presence of other co-factors such as hypovolemia, acidosis, or ischemia. CPK levels can be highly variable and are inconsistent with the degree of muscle damage; however, CPK is thought to be the most sensitive enzyme marker for muscle necrosis. Because of the potential life-threatening sequelae, exertional rhabdomyolysis should be included as a differential diagnosis when similar clinical and pathological signs are observed.

Alanine Transaminase↗

Hepatic effects in beagle dogs administered atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, for 2 years.

The chronic toxicity of atorvastatin (AT), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was evaluated in beagle dogs. Dogs were treated with 0, 10, 40, or 120 mg/kg of AT daily. Treatment lengths were 52 wk, 52 wk followed by 12 wk without drug, or 104 wk. Decreases in cholesterol levels were dose related and stable throughout the treatment period. Increases in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase were transient and dose related in severity at > or = 40 mg/kg. Two dogs administered 120 mg/kg of AT daily were sacrificed moribund during the first 9 wk of treatment. Hepatic lesions were reversible with or without continued treatment and dose related in severity and distribution. Hepatic microgranulomas and hepatocellular degeneration were seen at the 120-mg/kg dose in dogs sacrificed before 53 wk. Before 53 wk, hepatocellular lipofuscin deposits were increased in dogs given > or = 40 mg/kg of AT daily but were similar to controls after 12 wk without drug and after 104 wk of continuous treatment. Bile stasis occurred in dogs given > or = 40 mg/kg of AT daily at all time points but was less severe after reversal and at week 104 compared with week 52.

Alanine Transaminase↗

The biochemistry of runners in a 1600 km ultramarathon.

OBJECTIVE: To investigate biochemical changes related to muscle breakdown, hepatic damage, hyponatraemia, and a number of other variables in the serum of participants in a 1600 km ultramarathon run. METHODS: Blood samples were obtained from nine participants (seven men, two women) in a 1600 km foot race before, after 4 and 11 days of running, and at the conclusion of the event. Samples were analysed by standard methods and results corrected, where appropriate, for changes in plasma volume. RESULTS: Significant (p < 0.05) increases in the following variables were found during or at the conclusion of the event: plasma volume, sodium, chloride, urea, alkaline phosphatase, gamma-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, creatine kinase, bilirubin, total protein, albumin, glucose, calcium, and phosphate. Significant (p < 0.05) decreases in the following variables were found during or at the conclusion of the event: globulin, uric acid, and cholesterol. No change occurred in serum potassium, bicarbonate, creatinine, and triglycerides. CONCLUSION: A wide range of biochemical perturbations occur during ultramarathon running but a number of variables remain within normal limits despite severe physical stress. Large increases in plasma volume occur, and hyponatraemia is rare in events of this duration. The time course of increases in enzymic indicators of muscle damage indicates that duration of running is not the sole determinant of such increases. This study provides indirect evidence of possible hepatic damage during prolonged exercise and an increase in serum calcium both of which warrant further investigation.

Adult↗

Normal serum activities of liver enzymes in Swedish paint industry workers with heavy exposure to organic solvents.

The serum activities of the liver enzymes alanine aminotransferase, aspartate aminotransferase, ornithine carbamyl transferase, and gamma-glutamyl transferase were examined in 47 paint industry workers and unexposed age matched referents. The workers were exposed to a mixture of industrial solvents, of which xylene was the main component in most cases. The median total exposure was about 50% of Swedish 1981 threshold limit values according to measurements of individual solvent exposure performed at the same time. No differences in enzyme activities were shown either when the whole exposed and referent groups were compared or when the five workers with outstanding solvent exposures of five times the TLV or more were compared with their referents. It is concluded that in most workers the liver seems to remain largely undamaged from inhalation exposure to a commonly used mixture of non-chlorinated solvents. In many workers this seems to hold true even for high exposures for limited periods.

Adult↗

[Biochemical characteristics of hepatic functions in different clinical forms of chronic opisthorchiasis].

The main biochemical indices of hepatic functions (the activities of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, alpha-amylase, choline esterase and the concentrations of total bilirubin, cholesterol, and glucose) were studied in the sera of 256 patients with chronic opisthorchiasis. It was found that with diseases manifested in different clinical forms (cholangitis, cholecystitis, cholangiocholecystitis, cholangiohepatitis, cholecystitis in combination with pancreatitis), most study indices are within the normal ranges, but significantly differ from the means in a group of apparently healthy individuals. The findings suggest that such clinical forms of opisthorchiais as cholangiocholecystitis and cholangiohepatitis are characterized by manifestations of cytolysis and cholestasis, as cholecystitis is manifested by cytolysis, as cholecystitis in combination with pancreatitis, by cholestasis, and as cholangitis, by cholestasis and hepatic cell insufficiency. It is possible that further studies will provide evidence for how to correct detected disorders during pathogenetic therapy.

Adult↗

Fluvastatin reduced liver injury in rat model of extrahepatic cholestasis.

Inhibitors of 3-hydroxy-3methylglutarly coenzyme A, reductase, namely statins, exert pleiotropic actions beyond lipid-lowering effects. In ex vivo and in vitro studies, statins have antioxidative and antiinflammatory effects. Herein, we sought to determine whether treatment with fluvastatin (FV) would be beneficial in a rat model of common bile duct ligation (BDL)-induced liver injury. Female rats were subjected to a sham (n=10) or BDL (n=20). Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Three days after operation, rats subjected to CBDL were randomized to receive treatment with either FV (10 mg/kg) or saline every day over a 10 days experimental period. High levels of alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase decreased significantly (P<0.05) in animals treated with FV with compared to saline-administrated BDL animals. Compared with sham-operated rats, CBDL rats showed significantly higher levels of total nitrite and nitrate, malondihaldehyde, tumor necrosis factor alpha, myeloperoxidase, and lower concentrations of glutathione, superoxide dismutase, and catalase in the liver tissue (P<0.001). All of these changes were significantly attenuated (P<0.05) by treatment with FV after CBDL. CBDL was associated with increased apoptosis and nuclear factor kappa beta expression in saline-treated rats. Treatment with FV also decreased these parameters. These data support the view that FV ameliorates hepatic inflammation, lipid peroxidation, and tissue injury in rats subjected to CDBL. FV warrants further evaluation as an adjunctive treatment to ameliorate liver injury from extrahepatic biliary obstruction.

Alanine Transaminase↗

Diethylnitrosamine-induced metastasizing hepatocellular carcinomas in New Zealand white rabbits. A tumor model for clinical investigations.

The aim of this study was to produce large liver tumors reliably, and to diagnose the tumors during development. Therefore, New Zealand white rabbits were treated with N-nitrosodiethylamine orally three times per week by gavage and were examined by clinical-chemical assay at regular intervals during the average treatment period of 14 months. The total cumulative dose was 1200 mg N-nitrosodiethylamine over 14 months. After a short treatment period the initial dose of 3 mg/kg had to be reduced to 1.5 mg/kg. In all 11 treated animals (100%) liver tumors were seen at the end of the study. Four control animals did not show any neoplastic changes. Clinical parameters investigated were for an assessment of liver function, total protein, urea, creatinine, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin and neuraminic acid as well as some serum electrolytes. The in vivo diagnosis of liver tumors based on changes in these parameters proved to be relatively unreliable. The liver enzyme tests and urea concentration only yielded significant changes when the liver tumors were very large. Changes in neuraminic acid levels were the most reliable indicator for the presence of a liver tumor in this animal model. In the 11 treated animals, serum values of this marker increased towards the end of the study by an average of 300 mg/dl. The induced tumors were mainly hepatocellular carcinomas. Only in 1 animal was a hepatocellular adenoma found. Further primary tumors diagnosed were six adenomas in the kidneys and two uterus adenomas, as well as nasal cavity tumors (two papillomas, one carcinoma, one adenoma and one adenocarcinoma). In 70% of the treated rabbits the hepatocellular carcinomas had metastasized to the lungs.

Alanine Transaminase↗

Serum levels of soluble tumor necrosis factor receptors and effects of interferon therapy in patients with chronic hepatitis C virus infection.

OBJECTIVE: The aim of this study was to understand the significance of the tumor necrosis factor receptor (TNFR)-mediated signaling pathway in the pathophysiology of chronic hepatitis C. METHODS: The serum levels of soluble TNFRs (sTNFRs; sTNFR p55 and sTNFR p75) were measured in 84 patients with chronic hepatitis C virus (HCV) infection (24 sustained responders and 25 nonresponders to interferon [IFN] therapy and 35 patients with persistent normal blood chemistries) and 20 healthy controls, then compared with clinical parameters. RESULTS: The serum levels of sTNFRs increased in proportion to the severity of liver disease. The levels of sTNFRs revealed significant correlations with the serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and gamma-globulin, but not with the serum levels of HCV-core protein. In the sustained responder group, the levels of sTNFR p75 showed a significant decrease (p < 0.0002) 1 yr after IFN therapy, although the levels of sTNFR p55 did not. The levels of sTNFR p75 were correlated with the serum levels of macrophage-colony stimulating factor both before and after IFN therapy. In the nonresponder group, the levels of both sTNFRs were unaltered after IFN therapy. CONCLUSIONS: The TNF alpha-TNFRs system, especially the TNFR p75-mediated pathway, is involved in the hepatic inflammation-fibrosis process in chronic hepatitis C. The serum levels of sTNFR p75, but not sTNFR p55, were correlated with the serum levels of macrophage colony stimulating factor in this process.

Adult↗