Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 2-n-propyl (pr) and 2-n-butyl (bu) methylenedioxyindenes (MDIs) developed in our laboratories are intracellular calcium antagonists with coronary dilating and antiarrhythmic actions. Acute toxicity studies resulted, in mice, in an iv LD50 of 40 and 32 mg/kg for pr-MDI and bu-MDI, respectively, and an ip LD50 of 185 mg/kg for both MDIs. In rats, the ip LD50 was 175 and 240 mg/kg for pr-MDI and bu-MDI, respectively. An iv dose of 16 mg/kg decreased motor activity and prolonged barbiturate sleeping time in mice, but did not affect conditioned avoidance behavior or motor coordination tests. In sub-acute toxicity studies, rats received daily for 4 weeks 26.25 or 52.5 mg/kg ip of either MDIs, while mice received 23.13 or 46.25 mg/kg ip of either MDIs. No alterations were observed in serum alkaline phosphatase, glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, creatine phosphokinase, bilirubin, chloride, cholesterol, uric acid, prothrombin time, and bromsulphalein retention. Blood glucose was slightly lowered. Serum calcium was slightly lowered in male mice. The higher dose of pr-MDI elevated serum lactate dehydrogenase in rats. Both MDIs elevated serum isocitric dehydrogenase in male rats. Light microscopic examination of brain, kidney, liver, spleen, intestine, stomach, and myocardium showed no anomalies resulting from the 4-week MDI treatment, and electron microscopic examination of hepatocytes revealed no deleterious effects of either MDIs.
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PMID:Toxicological evaluation of new calcium antagonists: 2-substituted 3-dimethylamino-5,6-methylenedioxyindenes. 51 12

Serum biochemical parameters were studied in 42 healthy wild-caught adult tamarins (S. mystax), males and females, to determine the normal values. Blood samples were drawn repeatedly, and the serum was tested for aspartate aminotransferase, alanine aminotransferase, isocitric dehydrogenase, serum glucose, serum urea, triglyceride, cholesterol, albumin, and total protein. The results indicated that serum chemistry values were similar to those reported as normal for both humans and other Callitrichidae species. The study of serum biochemical parameters in tamarins with experimental hepatitis A indicated that serum enzyme activities alone reflected the hepatic damage, while other biochemical parameters were of no real clinical importance. The experimental results showed the levels of serum urea to be indicative of the pathological involvement of the kidneys in experimental hepatitis A in some cases.
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PMID:[The biochemical indices of the blood serum in experimental hepatitis A in tamarins]. 132 56

The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), acid phosphatase (ACP), lactate dehydrogenase (LDH) and isocitric dehydrogenase (ICD) in the serum of 60 healthy dromedary camels of either sex and different ages (one to 25 years) were determined. The results were analysed with respect to time of year (December-January and May-June), sex and age groups (below four years; four to 10 years; and over 10 years). The overall mean activities of AST, ALT, ALP, ACP, LDH and ICD were 36.1 +/- 0.35, 4.65 +/- 0.35, 27.21 +/- 0.43, 7.18 +/- 0.21, 479.0 +/- 7.33 and 7.74 +/- 0.17 iu litre-1, respectively. Activities of AST, ALT, ALP and ACP were significantly higher during extremely hot conditions (May-June) than in extreme cold (December-January) while the activity of LDH was higher in extremely cold conditions. Analysis of data based on sex revealed that AST, ALT and ALP activities in the serum of male animals were significantly higher than in female animals. The activities of all the enzymes were highest in animals under four years and then gradually decreased with age being lowest in the animals over 10 years.
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PMID:Activity of some enzymes in the serum of dromedary camels. 166 69

The effect of differences in sympathoadrenomedullary and pituitary-adrenocortical responses of individual animals to 35% hemorrhage on severity of shock induction has been studied in unanesthetized unrestrained rats by measuring plasma concentrations of adrenaline (A), noradrenaline (NA), corticosterone (CS) and adrenocorticotropin (ACTH). The responses of A, CS and ACTH were related to the decrease of blood volume and mean arterial pressure (MAP), whereas plasma NA remained unchanged. Higher susceptibility to blood loss was characterized by more pronounced hemorrhage-induced increase in blood lactate concentration and plasma enzyme activities as well as lethal outcome of hemorrhagic shock. In animals with irreversible hemorrhagic shock, enhanced catecholamine secretion and reduced ACTH release was observed. Furthermore, a revealed direct correlation between A and blood lactate concentration and plasma enzyme activities (aspartate aminotransferase, isocitric dehydrogenase, creatine kinase, lipase and glutathione-S-transferase) may indicate its possible participation in the mechanism of shock induction. In contrast, an inverse relationship of plasma CS to the indicators of shock severity was demonstrated. In conclusion, non-optimal neuroendocrine regulation of cardiovascular adjustments to hemorrhage in shock-prone animals might cause an exaggerated compensatory activation of adrenomedullary catecholamine secretion, which in turn has been shown to exert deleterious vascular and metabolic effects. The mechanisms responsible for reduced ACTH secretion in shock-prone animals remain to be established.
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PMID:Hormonal responses to hemorrhage and their relationship to individual hemorrhagic shock susceptibility. 216 2

There were significant changes in enzyme activities and concentrations of metabolites in the blood and liver of cows with fatty livers when compared to normal cows. Blood and liver samples were taken from cows at the abattoir immediately after slaughter. The liver was checked for pathological signs and the samples were divided according to the degree of fatty changes. Three groups were studied: controls showing no gross pathological signs, mild fatty infiltration and severe infiltration. In cows with fatty liver, there were significant increases in the serum activities of isocitric dehydrogenase (ICDH), glucose-6-phosphate dehydrogenase (G6PDH), glutamic dehydrogenase (GLDH), lactic dehydrogenase (LDH), malic dehydrogenase (MDH), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and acid phosphatase (ACP). In the fatty liver, the activities of the enzymes, ICDH, G6PDH, LDH, MDH, ALP and malic enzyme (ME) were significantly higher, while sorbitol dehydrogenase (SDH) was significantly lower. While serum total lipid decreased, the opposite was seen in the liver with higher lipid content, mainly due to triglycerides and cholesterol esters. The significant increases in the NADPH generating enzymes ME, ICDH, G6PDH and MDH, which are required for fatty acid synthesis, suggest that the lipids accumulated in the liver are not only of extrahepatic origin, mobilized into the liver, but also arise from increased lipid synthesis in the liver which is induced during the laying down of fat in the liver. Measurement of the serum NADPH generating enzymes may serve as a useful biochemical test specific for fatty liver in cows.
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PMID:Biochemical changes associated with the fatty liver syndrome in cows. 339 48

Common bile duct ligation (CBDL) in rats was used to induce liver disease and secondary kidney damage. The biochemical changes in the liver, kidney and plasma were studied at 3, 6, 10 and 21 days post CBDL. The observed alterations climaxed at the 6th day following ligation. Renal, activities of aldolase (ALD), lactic dehydrogenase (LDH), isocitric dehydrogenase (ICDH), sorbitol dehydrogenase (SDH), and alkaline phosphatase (ALP), were lowered in CBDL rats. Further, microsomal Na,K-ATPase and Mg-ATPase and mitochondrial oxidative-phosphorylation were inhibited. In the liver from CBDL rats the activities of aspartate aminotransferase (AST), Mg-ATPase and ALP were elevated, while SDH, ALD, malic dehydrogenase (MDH), LDH, malic enzyme (ME) and Na,K-ATPase were lowered. Plasma enzymes, AST, ALP, MDH, LDH, ALD, acid phosphatase (ACP) and ICDH and the metabolites bile acids, bilirubin, creatinine and urea were elevated. Addition of bile acids or bilirubin at concentrations comparable to those found in the plasma of CBDL rats, to the reaction mixture of the various enzymes strongly inhibited most, particularly mitochondrial oxidative phosphorylation. High concentrations of these substances in the blood may explain the development of renal failure during liver disease and its reversibility when liver function returns to normal.
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PMID:Biochemical changes in liver, kidney and blood associated with common bile duct ligation. 378 11

The effect of sodium salicylate (SS) pretreatment on acetaminophen (APAP) metabolism and hepatotoxicity in mice was studied. Mice were given a single oral dose of SS (100 mg/kg) 1 hr before graded doses of APAP (150-500 mg/kg). Liver histology, serum hepatic enzymes (serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase and isocitric dehydrogenase) and APAP metabolites in urine were examined 24 hr after APAP treatment. Free plasma APAP and liver glutathione were determined over 24 hr after treatment with 400 mg/kg of APAP alone or after SS pretreatment. At 500 mg of APAP per kg, mortality rate was 38% in SS + APAP group; no mortality was seen among animals treated with APAP alone. Centrilobular hepatic hemorrhagic necrosis and/or vacuolation were observed in both treatments. Mitosis of hepatocytes was increased in all APAP-treated mice. Incidence of hepatic necrosis and mean lesion grades at 300- and 500-mg/kg doses increased in mice pretreated with SS. Mice that received SS + APAP had significantly higher levels of serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase and isocitric dehydrogenase at all doses compared to mice treated with APAP alone. APAP glucuronide and sulfate conjugates decreased and APAP mercapturate conjugate increased in urine of mice receiving SS + APAP treatment. Free plasma APAP was significantly higher 2 hr after APAP treatment in SS + APAP-treated mice as compared to mice that received APAP alone. Hepatic glutathione levels were similarly decreased over 24 hr in both groups. These data demonstrate that SS pretreatment alters APAP biotransformation profile and potentiates the hepatotoxic effect of APAP in mice.
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PMID:Potentiation of the hepatotoxic effect of acetaminophen by prior administration of salicylate. 398 58

Feeder pigs weighing 12 to 15 kg each were given a single oral dose of aflatoxin, 1.2 mg/kg of body weight. Liver-specific serum enzyme activities were compared with gross, microscopic, and ultrastructural hepatic changes in individual pigs euthanatized at 24, 48, and 72 hours after they were given aflatoxin. The greater the morphologic change in liver of the treated pigs, the greater the increase in liver-specific serum enzyme activities. Isocitric dehydrogenase, alkaline phosphatase, sorbitol dehydrogenase, and aspartate aminotransferase activities increased in 6 of 8 treated pigs by 24 hours. Increase in gamma-glutamyl transpeptidase activity was not significant. Microscopic and ultrastructural changes in centrilobular hepatocytes included glycogen deletion, mitochondrial and endoplasmic reticulum swelling, membrane disruption, and nuclear fragmentation at 24 hours. The centrilobular areas had marked extravasation of erythrocytes at 24 hours without basal lamina changes. At 72 hours, the centrilobular hepatocytes had increased lipid vacuoles and acceptable amounts of glycogen. Marked infiltrations of monocytes, plasma cells, and lymphocytes were also present at this time.
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PMID:Acute aflatoxicosis in swine: clinical pathology, histopathology, and electron microscopy. 612 94

The accumulations by axoplasmic transport of selected enzyme activities proximal and distal to a ligature placed on the sciatic nerve were monitored in rats exposed in utero to maternal antibodies to nerve growth factor (NGF) and in control rats. Littermates of the animals exposed to anti-NGF were shown elsewhere to have had a 70% reduction in the number of sensory neurons in dorsal root ganglia and a 90% reduction in number of neurons in superior cervical (sympathetic) ganglion. The accumulation of F(-)-sensitive acid phosphatase activity was depressed 75% both proximal and distal to the tie. Accumulation of F(-)-resistant acid phosphatase activity was depressed nearly 50% proximal to the tie. Distal accumulation of this activity did not occur in either group of rats. Accumulation of acetylcholinesterase activity was depressed 30%. Distal accumulation of the activities of beta-glucuronidase and hexokinase was depressed 50%. In the lumbar dorsal root ganglia, dry weight was reduced 40%, and the activities of peroxide-sensitive, F(-)-resistant acid phosphatase and of the mitochondrial enzymes hexokinase, glutamic dehydrogenase, glutamic-oxalacetic transaminase, and NAD-dependent isocitric dehydrogenase were all reduced a little more, 45--50% per ganglion. However, the activities of the lysosomal enzymes, F(-)-sensitive acid phosphatase and beta-glucuronidase, of the peroxide-resistant, F(-)-resistant acid phosphatase, and of the mitochondrial enzyme glutaminase were all reduced about 60% per ganglion. The results of these measurements were interpreted to suggest that much, and perhaps all, of the F(-)-sensitive acid phosphatase activity in motion in peripheral nerve in rat is confined to sensory axons.
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PMID:Transported enzymes in sciatic nerve and sensory ganglia of rats exposed to maternal antibodies against nerve growth factor. 616 7

Groups of 8 male crossbreed domestic goats were given 3 dosage levels of aflatoxin B1 [(AFB1) mg/kg of body weight/day] orally: 0.1 for 34 days; 0.2 for 18 days; or 0.4 for 10 days. Clinical condition, feed consumption, and selected blood values were determined. Clinical signs of toxicosis included decreased feed consumption, slight-to-moderate loss of body weight, mucopurulent nasal discharge, dyspnea, coughing, lethargy, icterus, diarrhea (4 goats), and subnormal body temperature 24 to 48 hours before death. Clinicopathologic changes included increases in total RBC count, PCV, hemoglobin concentration, serum bilirubin concentration, and serum activities of aspartate aminotransferase, isocitric dehydrogenase, and ornithine carbamyl transferase. Goats given the 2 smaller dosage levels of AFB1 had slight increases of serum total protein (TP) concentration compared with control goats, but goats given the larger dosage levels of AFB1 initially had a slight decrease in TP. Aflatoxin had little effect on total WBC count. Serum alanine aminotransferase (ALT) activities in goats given the 2 larger dosage levels of AFB1 were similar to those of control goats, but goats given the smallest dosage level of AFB1 had increased serum ALT activities. Aflatoxin did not produce consistent dose-related changes in serum alkaline phosphatase activities. Seemingly, goats are susceptible to aflatoxin. Onset of clinical signs was dose-related. Onset and magnitude of increases in PCV, hemoglobin concentration, serum bilirubin concentration, and activities of serum aspartate aminotransferase, ornithine carbamyl transferase, and isocitric dehydrogenase were dose-related. Changes in TP and activities of serum ALT and alkaline phosphatase were neither dose-related nor were they potentially useful indicators of toxicosis.
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PMID:Caprine aflatoxicosis: experimental disease and clinical pathologic changes. 643 Jan 34


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