Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During L. donovani infection in golden hamsters, tremendous hepatic damage was observed as apparent from increased activities of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, succinate dehydrogenase, glucose-6-phosphatase and acid ribonuclease. The levels of cytochrome P-450 and related monooxygenases, viz. aniline hydroxylase and aminopyrine-N-demethylase registered significant decrease in infected animals. Sodium stibogluconate, a standard antileishmanial drug, though caused the removal of parasites from infected tissues, but did not help in the recovery of deranged hepatic markers. The results explain the higher mortality of stibanate treated infected animals as compared to untreated animals infected with L. donovani.
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PMID:Effect of sodium stibogluconate on hepatic mixed function oxidase system and marker enzymes of golden hamsters during Leishmania donovani infection. 931 42

Preliminary short-term toxicity studies of sucrose acetate isobutyrate (SAIB) in the dog demonstrated that addition of this additive to the diet was associated with an increase in liver size and elevated serum alkaline phosphatase activity with no evidence of pathological change by light microscopy. To determine the basis for these changes, a 12-week oral toxicity study of SAIB was conducted in the dog and a similar study was performed in the rat. SAIB was fed in the diet to groups of six beagle dogs of each sex at 0, 0.5, 1.0, 2.0 and 4.0%. SAIB was also fed to groups of 40 Sprague-Dawley rats of each sex at levels of 0, 2.5, 5.0 and 10.0%. In the rat study, in addition to routine toxicology parameters, hepatic microsomal enzyme induction was determined using a zoxazolamine hypnotic test, urinary ascorbic acid excretion and determination of hepatic carboxylesterase activity. Sodium phenobarbital was fed to groups of 20 rats of each sex at a dose of 100 mg/kg body weight/day by gavage as a positive control for hepatic microsomal enzyme induction. In the dog study, routine toxicological tests were supplemented by tests for bromsulfophthalein (BSP) retention, histochemical staining of liver sections for glycogen, phosphorylase, succinate dehydrogenase, and acid and alkaline phosphatases. Levels of liver lipid, protein, glycogen and carboxylesterase activity were also determined. Electron microscopic examinations were made on liver sections from the dog study at the end of the 12-week SAIB feeding period and after a 2-week withdrawal period. Administration of SAIB to rats did not reveal evidence of any effect on hepatobiliary function, and there was no indication of microsomal enzyme induction. Body weight gain of male rats fed SAIB was decreased, probably as the result of decreased palatability of the diet; SAIB did not affect body weight gain in females. The changes observed in the dogs fed SAIB included increased serum alkaline phosphatase activity with no change in serum alanine aminotransferase, aspartate aminotransferase or lactic dehydrogenase activity and no change in serum electrolyte, serum protein, glucose or bilirubin levels. No haematological changes were observed. BSP retention was observed at all SAIB dose levels. There were no SAIB-related pathological changes in any organ when examined by light microscopy. Examination by electron microscope revealed dilatation of bile canaliculi and an increase in smooth endoplasmic reticulum compared with controls. Histochemical studies also indicated increased enzyme activity of the bile canaliculi. The electron-microscope-revealed changes were completely reversed during a 2-week treatment withdrawal period. The dog study did not establish a no-effect level for changes in hepatobiliary function induced by feeding SAIB.
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PMID:Subchronic toxicity studies of sucrose acetate isobutyrate (SAIB) in the rat and dog. 951 48

Continuous warm blood cardioplegia was widely used, as an effective means of myocardial preservation, in open heart surgery. The comparisons of myocardial protective effects between traditional cold crystalloid and warm blood cardioplegia, however, have been based mainly on hemodynamics, cardiac function and myocardial metabolism, other than clinical outcome. The present study was designed to examine myocardial protective effects by assessing clinical outcome, enzyme levels and myocardial cytochemistry. Twenty patients undergoing heart valve replacement were divided randomly into two groups: Group I was given intermittent perfusion of cold crystalloid (St. Thomas Hospital solution) with hypothermic cardiopulmonary bypass (CPB) and Group II was given continuous administration of warm blood cardioplegia with normothermic CPB. The groups were similar with respect to sex, age, body surface area and preoperative ventricular function. Blood samples were obtained from an indwelling radial arterial catheter or from the arterial end of the oxygenator. Biopsy specimens from the right atrium were obtained immediately before aortic declamping (ischemic period) and 30 minutes after crossclamp removal (reperfusion period). Serum enzymes, including alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and its isoenzymes and creatine phosphokinase (CK) and its isoenzyme, were determined. Myocardial cytochemistry were chiefly assessed by grey-scale image processing of adenosine triphosphatase (ATPase), succinate dehydrogenase (SDH) and cytochrome oxidase (CCO) examinations. Relations among the results were discussed. Reperfusion time was reduced and ventilation support time decreased in Group II (33.50 +/- 3.78 min vs. 25.00 +/- 4.46 min, p < 0.05; 38.98 +/- 16.55 h vs. 19.84 +/- 1.11 h, p < 0.05). Rates of atrial beating during aortic crossclamp and spontaneous recovery to normal sinus rhythm were much higher in Group II than in Group I (80% vs. 20%, p < 0.05; 70% vs. 10%, p < 0.05). Differences in hospital morbidity and mortality between groups were nonsignificant. Serum AST, ALT, LDH and LDH1 + LDH2 all showed no significant intergroup differences. There was a higher serum CK-MB level with a delayed peak in Group II. The cytochemistry activities of ATPase was not different between groups and periods and SDH was the highest during reperfusion period in Group I and of CCO significantly much promoted in Group II in both periods. Continuous warm blood cardioplegia resulted in higher spontaneous recovery to sinus rhythm, shorter reperfusion and ventilation support time. Damage to the myocardium, skeletal muscle and liver always occur in warm blood cardioplegic patients. However, warm blood cardioplegia is still a practical method for myocardial preservation in open heart surgery.
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PMID:A generalized consideration of myocardial preservation with cold crystalloid versus warm blood cardioplegia in heart valve replacement. 961 11

Activated sludge is a rich source of nitrogenous matter and has been recommended as cheap supplement in animal feed. It has been incorporated into cattle and poultry feed. It is well known that sewage of purely domestic origin is also contaminated with heavy metals, pesticides, and other organic pollutants. A study was undertaken to determine the toxic effects of heavy metal-contaminated domestic sewage sludge on young male Wistar rats by supplementing dehydrated activated sludge in their diet at concentrations of 5, 10, 15 and 20%. The sludge was found to be contaminated with 1.820 (zinc), 0.273 (nickel), 0.017 (lead), 0.053 (copper), 0.006 (chromium), and 0.005 (cadmium)mg/g of dry sludge, by analysis by atomic absorption spectroscopy. The toxic effects of sludge-supplemented diets on individual groups of rats were assessed by assaying various enzyme activities in serum, liver, muscle, and brain. Levels of serum and liver alanine aminotransferase and succinate dehydrogenase (SDH) were significantly low in all the sludge-supplemented diet-fed (SSDF) rats. Similarly, serum lactate dehydrogenase (LDH) and muscle SDH activity were also significantly reduced in the SSDF rats. On the other hand, liver and muscle LDH, serum and liver aspartate aminotransferase, and serum and muscle alkaline phosphatase activities were significantly higher in all the SSDF animals. Brain and muscle acetylcholinesterase activity was significantly high in all the SSDF groups. This study indicates that even though the sludge is a rich source of nitrogenous matter, its supplementation in poultry and animals feed should be done with caution. Otherwise, the contaminants found in the sludge will biomagnify in the food chain and lead to various toxicological hazards.
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PMID:A study of toxic effects of heavy metal contaminants from sludge-supplemented diets on male Wistar rats. 1005 66

The effect of various metabolic inhibitors on the rate of oxygen consumption by procyclic culture forms of Trypanosoma congolense utilizing proline as substrate was investigated. Cyanide inhibited the rate of oxygen consumption by 81.0 +/- 6.7%, malonate inhibited the rate by 51.6 +/- 1.6% and Antimycin A by 73.1 +/- 5.9%. A combination of cyanide and malonate inhibited the rate of oxygen consumption by 84.9 +/- 6.7% while a combination of antimycin A and malonate inhibited the rate by 81.6 +/- 7.6%. Rotenone had no effect on the rate of respiration except when the intact cells were first permeabilized by digitonin after which rotenone decreased the rate of respiration by 20-30%. Salicylhydroxamate (SHAM) did not have any effect on the rate of oxygen consumption. Enzymes involved in the catabolism of proline with high activities were: proline dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase, NADP-linked malic enzyme, alanine aminotransferase and malate dehydrogenase. Activities of 1-pyrroline-5 carboxylate dehydrogenase, glutamate dehydrogenase, aspartate aminotransferase and NAD-linked malic enzyme were detectable but lower. The end products of proline catabolism were alanine and glutamate. Unlike the case in Trypanosoma brucei brucei aspartate was not detected. Possible pathways of proline catabolism in procyclic culture forms of T. congolense and of electron transfer are proposed.
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PMID:Catabolism of proline by procyclic culture forms of Trypanosoma congolense. 1042 13

Tamoxifen (TAM) is used in the treatment of breast cancer and decreases the incidence of breast cancer when given to healthy women for different therapeutic purposes. This expansion of its use calls for further studies of its own potential side effects and those in combination with other prescription drugs. Diazepam (DP) is one such drug normally administered to patients who are under cancer treatment and those who suffer from insomnia. The present study examines the effect of individual and simultaneous administration of TAM and DP at therapeutic dose level of 0.8 mg/Kg/day of TAM and 0.3 mg/Kg/day of DP to normal female Wistar rats for a period of 12 weeks. The drugs were administered orally by mixing it in pellet made by wheat dough. There was no significant change in the terminal body weight and liver weights of animals. The ovary weights in TAM + DP treated animals were significantly decreased. The serum succinate dehydrogenase (SDH) levels were significantly lower in TAM, DP and TAM + DP treated rats and comparatively were lowest in TAM and TAM + DP treated animal groups. Serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), acid and alkaline phosphatase (ACP & ALP) levels were significantly higher in the three treated groups, but comparatively lower in TAM + DP treated animals when compared to TAM or DP alone treated rats. There was marked increase in liver triglyceride and cholesterol levels in the three treated groups but remarkable decrease in liver glycogen. Total serum cholesterol levels were significantly high in DP and TAM + DP treated rats and total serum triglyceride levels were significantly high only in TAM treated rats. As a whole it can be concluded that DP does not enhance TAM toxicity on simultaneous administration, but on its own when administered individually brings about perturbation in lipid storage and metabolism.
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PMID:A toxicity study of simultaneous administration of Tamoxifen and Diazepam to female Wistar rats. 1066 14

Phthalate esters have been implicated as xenoestrogens. One among them is di-ethylphthalate (DEP), which is used as plasticizer, detergent base, and binder in incense sticks and after-shave lotions. DEP is one of the contaminants of freshwater and marine ecosystems. Incense stick workers are occupationally exposed to DEP and some workers are chronic alcoholics. Therefore, a study was undertaken to evaluate the interactive toxicity of DEP with ethyl alcohol (EtOH) in young male Sprague-Dawley rats. The rats were given 50 ppm DEP (w/v), 5% EtOH (v/v) and a combined dose of 50 ppm DEP (w/v)+EtOH (5% v/v) in water ad libitum for a period of 120 days and were maintained on normal diet. Control animals received normal diet and plain water. During the treatment rats were weighed every week and water consumption per day was measured. After the completion of treatment, liver weight/body weight, liver weight, body weight, serum enzymes and other biochemical parameters were assessed. It was found that there was no significant change observed in body weight, liver weight, liver weight/body weight and water consumption. It was observed that there was a significant decrease in liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in EtOH, DEP and EtOH+DEP treated rats in the order of EtOH>DEP>EtOH+DEP as compared with control. Serum AST, ALT, acid phosphatase (ACP), alkaline phosphatase (ALP), succinate dehydrogenase (SDH) and liver ACP showed significant increase in DEP and EtOH+DEP treated rats in the order of DEP>EtOH+DEP as compared with control and EtOH treated rats. On the contrary, there was no significant change in liver ALP levels in treated rats. There was significant increase in liver SDH, glycogen, total triglyceride, total cholesterol and lipid peroxidation in DEP and EtOH+DEP treated rats, but no significant changes in the serum SDH, glucose and total triglyceride levels. Serum total cholesterol levels in DEP and EtOH+DEP treated rats were significantly high as compared to control and EtOH treated rats. These results show that there is no interaction of DEP with EtOH but DEP alone leads to severe impairment of lipid metabolism coupled with toxic injury to the liver as evident from significantly altered lipid and enzyme levels in the liver and serum. Long term simultaneous exposure to DEP and EtOH may have severe implications for humans who are occupationally exposed to these two xenobiotics.
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PMID:Simultaneous administration of diethylphthalate and ethyl alcohol and its toxicity in male Sprague-Dawley rats. 1083 29

1) The oxygen consumption increases during Bufo bufo development in accordance with the two steps which border at the "heart beat" stage. 2) Cytochrome c oxidase activity is not proportional to the oxygen consumption: it is notable and constant in the first step, and it only increases in the second. 3) In the mitochondria of preneural embryos, citrate synthase, NADP+ dependent isocitrate dehydrogenase, and succinate dehydrogenase activities are very low in respect to malate dehydrogenase and glutamate oxaloacetate transaminase activities. The Krebs cycle results lowered at the condensing reaction level with acetyl accumulation when pyruvate is available. The same behavior has been observed in the Xenopus laevis oocytes and differentiated tissues. 4) The presence of a phosphagen system which is different from creatine phosphate and arginine phosphate, supporting ATP level, has been demonstrated in B. bufo embryos. 5) Mitochondria of postneural embryos are able to accomplish a complete Krebs cycle by increasing citrate synthase, and succinate dehydrogenase activities. 6) In all B. bufo development, malate dehydrogenase and glutamate oxaloacetate transaminase constitute a multienzymatic system by which the mitochondria accomplish a decarboxylic amino acid shunt required for the transformation of deutoplasm into protoplasm. This shunt is also operative in the X. laevis oocytes. 7) Through pyruvate production, by oxidative decarboxylation of malate, the NAD(P)+ dependent malic enzyme could carry out a fundamental anaplerotic function in the mitochondria which is specialized in the production of biosynthetic blocks belonging to the embryo in which the carbohydrates metabolism rather than the glycolytic activity is designed for pentose phosphate and glycerol phosphate synthesis for protein and cytomembrane production. 8) Consistent metabolic differences have been highlighted between B. bufo embryos and X. laevis embryos.
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PMID:Physiological differentiation of the mitochondria during Bufo bufo development. 1125 8

The efficacy of Tiron (4,5-dihydroxybenzene 1,3-disulfonic acid disodium salt) was examined in the treatment of beryllium-induced maternal and developmental toxicity in rats. Single administration of beryllium nitrate at a dose of 50 mg/kg (i.m.) on day 13 of gestation caused reductions in fetal and placental weights, the number of implantation sites and number of corpora lutea, as well as causing post-implantation loss, stunted growth, increase in the number of resorptions, and also a disturbed sex ratio. Maternal toxicity was demonstrated by reduction in body weight gain. Administration of beryllium also showed significant alteration in the hematological and biochemical indices of the mother as well as the fetus. Marked decreases were recorded in hemoglobin percentage, blood sugar levels, serum protein contents and serum alkaline phosphatase activity. By contrast, significant elevation was found in the activity of transaminases (aspartate aminotransferase and alanine aminotransferase). Tissue protein contents, glycogen contents, activities of alkaline phosphatase, adenosine triphosphatase and succinic dehydrogenase of kidney, lungs and uterus, and maternal and fetal liver all showed significantly decreased values after beryllium exposure, and remarkable elevation was observed in acid phosphatase, glucose-6-phosphatase and hepatic lipid peroxidation. These parameters were restored considerably with administration of 471 mg/kg i.m. Tiron from days 14 to 18 of gestation. Atomic absorption spectrophotometry also revealed a high concentration of beryllium in different organs of pregnant rats. Interestingly, a small amount of metal ion was also detected in the fetus and reduced accumulation of beryllium was noticed after Tiron treatment.
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PMID:Protective effect of Tiron (4,5-dihydroxybenzene-1,3-disulfonic acid disodium salt) against beryllium-induced maternal and fetal toxicity in rats. 1218 11

A 9-month-old male German Shepherd dog was referred for evaluation of progressive exercise intolerance. Clinical examination revealed a stiff, stilted gait and marked atrophy and hypotonia of skeletal muscle. The dog had raised creatine kinase (181 U/liter), lactate dehydrogenase (510 U/liter), and aspartate aminotransferase (123.6 U/liter) levels, suggesting a muscle disease. Histochemical evaluation of muscle biopsies revealed the presence of subsarcolemmal oxidative activity, reduced nicotinamide adenine dinucleotide, and succinate dehydrogenase, and the absence of cytochrome oxidase activity. Ragged red fibers were demonstrated with Gomori trichrome stain. Ultrastructural examination of the muscle confirmed the presence of subsarcolemmal accumulations of mitochondria and morphologically atypical mitochondria.
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PMID:Mitochondrial myopathy in a german shepherd dog. 1294 7


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