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:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cisplatin [cis-dichlorodiammineplatinum (II)] is a widely used chemotherapeutic drug that is toxic to the kidney. Concurrent administration of cysteine together with vitamin E, Crocus sativus and Nigella sativa reduced the toxicity of cisplatin in rats. When administered i.p. for 5 alternate days with 3 mg/kg cisplatin, cysteine (20 mg/kg) together with vitamin E (2 mg/rat) an extract of Crocus sativus stigmas (50 mg/kg) and Nigella sativa seed (50 mg/kg) significantly reduced blood urea nitrogen (BUN) and serum creatinine levels as well as cisplatin-induced serum total lipids increases. In contrast, the protective agents given together with cisplatin led to an even greater decrease in blood glucose than that seen with cisplatin alone. The serum activities of alkaline phosphatase, lactate dehydrogenase, malate dehydrogenase, aspartate aminotransferase and alanine aminotransferase of cisplatin-treated rats were significantly decreased, whereas the activities of glutathione reductase and isocitrate dehydrogenase were significantly increased. Addition of cysteine and vitamin E, Crocus sativus and Nigella sativa in combination with cisplatin partially prevented many changes in the activities of serum enzymes. In cisplatin-treated rats, the liver activities of isocitrate dehydrogenase and aspartate aminotransferase were significantly increased, whereas much greater changes were found in the kidneys, with increased activity of glucose-6-phosphate dehydrogenase and decreased activities of alkaline phosphatase, isocitrate dehydrogenase, malate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, sorbitol dehydrogenase and gamma-glutamyl transferase, as well as a decreased phosphorylation to oxidation ratio in the mitochondria, indicating reduced adenosine triphosphate production. Also, administration of cysteine and vitamin E, Crocus sativus and Nigella sativa together with cisplatin partially reversed many of the kidney enzymes changes induced by cisplatin. Cysteine together with vitamin E, Crocus sativus and Nigella sativa tended to protect from cisplatin-induced falls in leucocyte counts, haemoglobin levels and mean osmotic fragility of erythrocytes and also prevented the increase in haematocrit. The results of this study indicate a basis for the toxic effects of cisplatin, and suggest a possible way of counteracting the toxicity by introducing protective agents such sulphydryl compounds, other antioxidants and extracts of natural products. It also appears that cells adapt to the effects of cisplatin through the induction of systems that produce NADPH, which in turn compensates the decrease of free sulphydryl groups. We conclude that cysteine and vitamin E, Crocus sativus and Nigella Sativa may be a promising compound for reducing cisplatin-toxic side effects including nephrotoxicity.
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PMID:Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. 960 69

Severe iron deficiency results in complex systemic disorders e.g., including metabolism of energy and minerals. To investigate whether also moderate iron depletion may alter the activities of citric cycle enzymes and the cytochrome oxidase, the trace element status, and serum enzymes indicative of cell damage, this experiment was carried out with rats supplied with sub-optimal iron (9, 13 and 18 mg iron per kg diet) over a total of 5 weeks. The study included 3 pair-fed groups and an ad libitum group, fed with 50 mg iron/kg diet. All iron-restricted rats were classified as iron-deficient on the basis of reduced iron concentrations in body and iron-depending blood parameters. Body weight gain and catalase activity in kidney were lowered in rats receiving the lowest dietary iron level, exclusively. Rats fed 9 and 13 mg iron per kg diet had nearly 6- and 3-fold, respectively higher platelet counts in blood than their corresponding pair-fed controls. The activities of transaminases ASAT and ALAT, alkaline phosphatase, glutamate dehydrogenase and lactate dehydrogenase in serum which are indicative of cell damage were also markedly influenced by moderate dietary iron restriction, in which the enzyme levels in serum increased with intensifying iron depletion. Although, moderate iron restriction to young male rats was associated with marked alterations in iron status and serum enzymes, the activities of tricarboxylic acid cycle enzymes including malic dehydrogenase, fumarase, and isocitric dehydrogenase as well as cytochrome oxidase in liver remained largely unaffected. Only hepatic aconitase showed a somewhat reduction with iron depletion. Moreover, iron restriction was also accompanied with an accumulation of copper in liver which was significant for rats fed 9 and 13 mg iron per kg diet, whereas zinc status remained completely unaffected by moderate iron deficiency. It can be concluded, that a short-term moderate iron deficiency with ranging hemoglobin concentrations from 66 and 121 g/L, was accompanied with altered platelet counts, serum enzyme activities indicative of cell damage, and hepatic copper concentrations, but the activities of the tricarboxylic acid cycle enzymes and cytochrome oxidase in liver remained largely unaffected.
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PMID:Effect of different degrees of moderate iron deficiency on the activities of tricarboxylic acid cycle enzymes, and the cytochrome oxidase, and the iron, copper, and zinc concentrations in rat tissues. 980 Mar 17

Affinity adsorbents based on immobilized triazine dyes offer important advantages circumventing many of the problems associated with biological ligands. The main drawback of dyes is their moderate selectivity for proteins. Rational attempts to tackle this problem are realized through the biomimetic dye concept according to which new dyes, the biomimetic dyes, are designed to mimic natural ligands. Biomimetic dyes are expected to exhibit increased affinity and purifying ability for the targeted proteins. Biocomputing offers a powerful approach to biomimetic ligand design. The successful exploitation of contemporary computational techniques in molecular design requires the knowledge of the three-dimensional structure of the target protein, or at least, the amino acid sequence of the target protein and the three-dimensional structure of a highly homologous protein. From such information one can then design, on a graphics workstation, the model of the protein and also a number of suitable synthetic ligands which mimic natural biological ligands of the protein. There are several examples of enzyme purifications (trypsin, urokinase, kallikrein, alkaline phosphatase, malate dehydrogenase, formate dehydrogenase, oxaloacetate decarboxylase and lactate dehydrogenase) where synthetic biomimetic dyes have been used successfully as affinity chromatography tools.
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PMID:Biomimetic dyes as affinity chromatography tools in enzyme purification. 1099 23

Fluorescence microscopy was used to visualize the accumulated fluorescent product of the enzyme alkaline phosphatase to indicate where active covalently bound enzyme remained on the surface after application of a Nd: YAG laser interference pattern to a surface that was first globally derivatized with the covalently bound enzyme. The electrochemical kinetics of the same carbon fiber surface were examined through the electrogenerated chemiluminescence of Ru(bpy)(3)2+ to determine that electron-transfer sites were indeed segregated from the enzyme-binding sites. The enzyme-derivatized areas are determined to be separate and distinct from the areas of enhanced electron transfer. Two other enzymes, glucose oxidase and malic dehydrogenase, were then covalently bound to carbon fiber microelectrode surfaces in order to verify the change in detection limit of their respective cofactors, NADH or H2O2, under a variety of surface conditions. The S/N of an enzyme-modified electrode after laser interference pattern photoablation and electrocatalytic treatment is improved by more than 1 order of magnitude over that observed at an electrode that is globally enzyme modified.
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PMID:Laser interference pattern ablation of a carbon fiber microelectrode: biosensor signal enhancement after enzyme attachment. 1105 9

Cellular energetics and redox status were evaluated in NRK-52E cells, a stable cell line derived from rat proximal tubules. To assess toxicological implications of these properties, susceptibility to apoptosis induced by S-(1,2-dichlorovinyl)-L-cysteine (DCVC), a well-known mitochondrial and renal cytotoxicant, was studied. Cells exhibited high activities of several glutathione (GSH)-dependent enzymes, including gamma-glutamylcysteine synthetase, GSH peroxidase, glutathione disulfide reductase, and GSH S-transferase, but very low activities of gamma-glutamyltransferase and alkaline phosphatase, consistent with a low content of brush-border microvilli. Uptake and total cellular accumulation of [14C]alpha-methylglucose was significantly higher when cells were exposed at the basolateral as compared to the brush-border membrane. Similarly, uptake of GSH was nearly 2-fold higher across the basolateral than the brush-border membrane. High activities of (Na(+)+K(+))-ATPase and malic dehydrogenase, but low activities of other mitochondrial enzymes, respiration, and transport of GSH and dicarboxylates into mitochondria were observed. Examination of mitochondrial density by confocal microscopy, using a fluorescent marker (MitoTracker Orange), indicated that NRK-52E cells contain a much lower content of mitochondria than rat renal proximal tubules in vivo. Incubation of cells with DCVC caused time- and concentration-dependent ATP depletion that was largely dependent on transport and bioactivation, as observed in the rat, on induction of apoptosis, and on morphological damage. Comparison with primary cultures of rat and human proximal tubular cells suggests that the NRK-52E cells are modestly less sensitive to DCVC. In most respects, however, NRK-52E cells exhibited functions similar to those of the rat renal proximal tubule in vivo.
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PMID:Cellular energetics and glutathione status in NRK-52E cells: toxicological implications. 1241 66

Thirty-one urease-positive thermophilic Campylobacter (UPTC) isolates, including three reference strains (NCTC12892, NCTC12895 and NCTC12896), and three Campylobacter lari isolates, which were isolated from several countries and sources, were compared genotypically by using multilocus enzyme electrophoresis (MLEE). We examined allelic variation around seven enzyme loci, including the adenylate kinase, alkaline phosphatase, catalase, fumarase, malic enzyme, malate dehydrogenase, and L-phenylalanyl-L-leucine peptidase loci. MLEE typing revealed the presence of 23 different electrophoretic types (ETs) among the 31 UPTC isolates, and 14 isolates shared six electrophoretic profiles. Three different ETs were identified for the three C. lari isolates examined, and no ETs were shared by UPTC and C. lari isolates. Quantitative analyses were subsequently performed by using allelic variation data, and the results demonstrated that the mean genetic diversity was 0.655. In conclusion, MLEE demonstrated that the UPTC isolates examined are genetically hypervariable and form a cluster separate from the C. lari cluster.
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PMID:Characterization of urease-positive thermophilic Campylobacter subspecies by multilocus enzyme electrophoresis typing. 1278 30

Adriamycin, which is widely used in the treatment of various neoplastic conditions, exerts toxic effects in several organs. Adriamycin nephrotoxicity has been recently documented in a variety of animal species. The present study was designed to investigate the effect of lipoic acid on the nephrotoxic potential of adriamycin. The study was carried out with adult male albino rats of Wistar strain. Test animals were divided into four groups of six rats each as follows: Group I (control) received only normal saline throughout the course of the experiment. Group II (ADR) received intravenous injections of adriamycin through the tail vein (1 mg kg(-1) body wt day(-1)) once a week for a period of 12 weeks. Group III (LA) received lipoic acid (35 mg kg(-1) body wt day(-1)) intraperitoneally once a week for a period of 12 weeks. Group IV (ADR + LA) received a single injection of lipoic acid intraperitoneally 24 h prior to the administration of adriamycin through the tail vein once a week for a period of 12 weeks. Intravenous injections of adriamycin resulted in decreased activities of the glycolytic enzymes; hexokinase, phosphoglucoisomerase, aldolase and lactate dehydrogenase in the rat renal tissue. The gluconeogenic enzymes, glucose-6-phosphatase and fructose-1,6-diphosphatase, showed a decline in their activities on adriamycin administration. The transmembrane enzymes namely the Na+,K+-ATPase, Ca2+-ATPase, Mg2+-ATPase and the brush-border enzyme alkaline phosphatase also showed a decrease in their activities. This decrease in the activities of ATPases and alkaline phosphatase suggests basolateral and brush-border membrane damage. Decreased activities of the TCA cycle enzymes isocitrate dehydrogenase, succinate dehydrogenase and malate dehydrogenase, suggest a loss in mitochondrial function and integrity. Nephrotoxicity was evident from the increased excretions of N-acetyl-beta-D-glucosaminidase and gamma-glutamyl transferase in the urine of adriamycin administered rats. These biochemical disturbances were effectively counteracted on pre-treatment with lipoic acid, which brought about an increase in the activities of glycolytic enzymes, ATPases and the TCA cycle enzymes. On the other hand, the gluconeogenic enzymes showed a further decrease in their activities on lipoic acid pretreatment. LA pretreatment also restored the activities of the urinary enzymes to normal. These observations shed light on the nephroprotective action of lipoic acid rendered against experimental aminoglycoside toxicity.
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PMID:The influence of lipoic acid on adriamycin induced nephrotoxicity in rats. 1284 26

This study examined the possibility of using striped field mice as a biological dosimeter or indicator for surveillance of the ecological effects of boundary radiation emitted by nuclear power plants. For this study, the external morphological characteristics and isoenzymic electrophoretypes of Korean domestic dark-striped field mice were studied after they were captured, controlled for reproduction, and their exact species were identified. In terms of morphological external characteristics, the dark-brown coat, dark back stripe, head-to-tail length, tail length, and ear length matched the taxonomical characteristics of dark-striped field mice. In terms of isoenzymic electrophoretypes, the analyses on I-lactate dehydrogenase, aspartate aminotransferase, and malate dehydrogenase revealed that one species of dark-striped field mice, called Apodemus agrarius coreae, was scattered throughout a wide range of habitats. On the other hand, after irradiating the A. a. coreae (0, 0.5, 1, 3, 5, and 7 gray [Gy]) to analyze their survival rate and frequency of micronuclei in peripheral polychromatic erythrocytes, their LD50/30 was approximately 5 Gy. Also, the mice that contained 1 or 3 Gy gained weight compared with those that contained 0.5 Gy. Moreover, those with 0.5 Gy and higher showed an increase in white blood cells and platelets as well as in sodium and creatinine. However, decreased concentrations of alkaline phosphatase, alanine animotransferase, calcium, phosphorus, and globulin were observed in the A. a. coreae after irradiation. The results of the study reveal that wild A. a. coreae mice have high potential as a biological monitoring system to determine radiation effects in human environments such as those within the vicinity of nuclear power plants.
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PMID:Potential of dark-striped field mice, Apodemus agrarius coreae, for use as a biological radiation dosimeter for human environments. 1686 42

During Ramadan, Muslims the world over abstain from food and water from dawn to sunset for a month. We hypothesised that this unique model of prolonged intermittent fasting would result in specific intestinal and liver metabolic adaptations and hence alter metabolic activities. The effect of Ramadan-type fasting was studied on enzymes of carbohydrate metabolism and the brush border membrane of intestine and liver from rat used as a model. Rats were fasted (12 h) and then refed (12 h) daily for 30 d, as practised by Muslims during Ramadan. Ramadan-type fasting caused a significant decline in serum glucose, cholesterol and lactate dehydrogenase activity, whereas inorganic phosphate increased but blood urea N was not changed. Fasting resulted in increased activities of intestinal lactate (+34%), isocitrate (+63%), succinate (+83%) and malate (+106%) dehydrogenases, fructose 1,6-bisphosphatase (+17%) and glucose-6-phosphatase (+22%). Liver lactate dehydrogenase, malate dehydrogenase, glucose-6-phosphatase and fructose 1,6-bisphosphatase activities were also enhanced. However, the activities of glucose-6-phosphate dehydrogenase and malic enzyme fell significantly in the intestine but increased in liver. Although the activities of alkaline phosphatase, gamma-glutamyl transpeptidase and sucrase decreased in mucosal homogenates and brush border membrane, those of liver alkaline phosphatase, gamma-glutamyl transpeptidase and leucine aminopeptidase significantly increased. These changes were due to a respective decrease and increase of the maximal velocities of the enzyme reactions. Ramadan-type fasting caused similar effects whether the rats fasted with a daytime or night-time feeding schedule. The present results show a tremendous adaptation capacity of both liver and intestinal metabolic activities with Ramadan-type fasting in rats used as a model for Ramadan fasting in people.
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PMID:Influence of Ramadan-type fasting on enzymes of carbohydrate metabolism and brush border membrane in small intestine and liver of rat used as a model. 1718 84

Gentamicin (GM) is an aminoglycoside antibiotic commonly used against life threatening gram negative bacterial infections, however, nephrotoxicity remains the major concern for its long term use. Although its effects on kidney are well characterized but there have been no studies regarding its effects on intestine. We hypothesize that GM causes adaptive coordinated effect on enzymes of carbohydrate metabolism and terminal digestion/ absorption in rat intestine. Rats were administered a nephrotoxic dose of GM (80 mg /kg body weight) daily for 15 days and a time dependent effect was observed on various enzyme activities. Activities of lactate (LDH), malate (MDH) and isocitrate (ICDH) dehydrogenases, significantly increased and peaked at different time intervals of GM treatment. Whereas LDH activity remained higher, MDH and ICDH activity slowly declined from their peak values. Activities of fructose-1,6-bisphosphatase, glucose-6-phosphatase and glucose-6-phosphate dehydrogenase increased but malic enzyme decreased in a time dependent manner. Activity of alkaline phosphatase and sucrase significantly increased but gamma-glutamyl transpeptidase activity decreased. GM administration increased lipid peroxidation, glutathione peroxidase but decreased superoxide dismutase and catalase activities. The results indicate that GM treatment selectively upregulated certain enzymes of carbohydrate metabolism and terminal digestion/absorption and perturbed antioxidant defenses.
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PMID:Time dependent effect of gentamicin on enzymes of carbohydrate metabolism and terminal digestion in rat intestine. 1788 63


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