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)

Humans are exposed to a number of toxic elements in the environment; however, most experiments with laboratory animals investigate only one toxic element. To determine if concomitant exposure to lead (Pb), cadmium (Cd), and/or arsenic (As) modified the changes produced by any one metal in various parameters of toxicity, 168 male, Sprague-Dawley, young adult rats were fed nutritionally adequate diets to which had been added 0 or 200 ppm Pb as Pb acetate, or 50 ppm Cd as Cd chloride, or 50 ppm As as sodium arsenate or arsanilic acid in a factorial design for a period of 10 weeks. At these concentrations, Cd and As reduced weight gain even when differences in food intake were taken into account; administration of both Cd and As depressed weight gain more than did either metal alone. Pb did not adversely affect food consumption or weight gain. Increased numbers of red blood cells (RBCs) were observed following administration of Pb, Cd, or As; usually more cells were observed when two or three metals were administered, compared to individual metals. Despite increasing numbers of circulating RBCs, hemoglobin and hematocrit were reduced, especially with the Pb-Cd combination and the Cd-arsanilic acid combination. Specific effects of Pb on heme synthesis were observed, including increased urinary excretion of delta-aminolevulinic acid; this increase was reduced by the presence of dietary cadmium. Analyses of blood showed values for the laboratory rat within normal ranges for blood urea nitrogen, creatinine, cholesterol, calcium, albumin, total protein, and bilirubin. Uric acid was increased by Pb, with little modification by dietary Cd or As content. Serum glutamate-oxalate transaminase activity was reduced by As. Serum alkaline phosphatase was greatly reduced by either As or Cd but not Pb. Combinations of As and Cd did not further reduce the activity of this enzyme. Kidney weight and kidney weight/body weight ratios were increased by Pb alone, with no effects of Cd or As alone or as interactions. Liver weight/body weight ratios were reduced in animals fed 50 ppm dietary Cd. Kidney histology shows predominantly Pb effects, namely, intranuclear inclusion bodies and cloudy swelling. Ultrastructural evaluation of kidneys from Pb-treated animals disclosed nuclear inclusion bodies of the usual morphology and mitochondrial swelling. Concurrent administration of Cd greatly minimized Pb effects on the kidney under conditions of this experiment. Liver histology suggests an increased rate of cell turnover with either As compound, but few specific changes.
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PMID:Effects of concurrent administration of lead, cadmium, and arsenic in the rat. 19 3

Studies on aspartate aminotransferase (GOT) and L-alanine aminotransferase (GPT) of Paramphistomum explanatum have shown that GPT activity has more than twice the activity of GOT. The effect os some--SH reagents like cadmium, mercury, silver and iodoacetamide revealed that both enzymes were inhibited except that GOT was insensitive to cadmium ions. GPT was found to be much more sensitive to--SH reagents than GOT. There was unusual reaction to the two thiols used, cysteine and mercaptoethanol. Cysteine inhibited both the enzymes and mercaptoethanol activated GPT and inhibited GOT. Thiols in combination with iodoacetamide showed that the strong inhibitory effect of cysteine on both enzymes was reduced by iodoacetamide, but with mercaptoethanol the inhibitory effect on GOT was greater than when either of them was used alone, while GPT the effect of either counteracted each other. EDTA activated both enzymes and partially protected mercury inhibition of both enzymes and silver inhibition GOT only. It provided no protection against silver inhibition of GPT but complete protection of GPT against total inhibition by cadmium ions.
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PMID:Effect of some--SH and other reagents on aspartate aminotransferase and L-alanine aminotransferase of Paramphistomum explanatum Fischoeder, 1901. 41 89

The comparative renal toxicity of rats after injection of cadmium (Cd) and zinc (Zn)-metallothioneins (MTs) with different Cd/Zn ratios at the same dose of 200 micrograms MT-bound Cd/kg was studied. From determination of the urinary excretion of protein, aspartate aminotransferase (AST) and glucose, which are indices of Cd-induced renal damage, the extent of the renal toxicity of the MTs used here was in the order (1 Cd/0Zn)-MT = (2Cd/1Zn)-MT greater than (1Cd/2Zn)-MT greater than (1Cd/6Zn)-MT. The characterization of Cd, Zn and Cu in the urine after injection of MTs was examined using a Sephadex G-75 column. (1Cd/0Zn)-MT injection showed that Cd was present mainly in lower-molecular-weight fractions, with only small amounts of Cd in the MT fraction. Upon injection of other MTs, Cd was present mainly in the MT fraction and increased with decreasing Cd/Zn ratio. Zn was present mainly in lower-molecular-weight fractions and Cu mainly in the MT fraction, indicating the replacement of MT-bound Zn by Cu. The cumulative urinary excretion of Cd during 12 days after injection of MTs decreased with increasing Cd/Zn ratio. The Cd content of the kidney and liver increased with increasing Cd/Zn ratio. The results of this study indicate that in rats injected with MTs with different Cd/Zn ratios, the renal uptake of Cd increases with increasing Cd/Zn ratio, resulting in more severe renal damage.
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PMID:Comparative renal toxicity of metallothioneins with different cadmium/zinc ratios in rats. 201 79

Lipoate (thioctic acid) is presently used in therapy of a variety of diseases such as liver and neurological disorders. However, nothing is known about the efficacy of lipoate and its reduced form dihydrolipoate in acute cadmium (Cd2+) toxicity which involves severe liver disturbances. Therefore, we investigated the effects of these redox compounds on Cd2(+)-induced injuries in isolated rat hepatocytes. The cells were coincubated with 150 microM Cd2+ and either 1.5-6.0 mM lipoate or 17-89 microM dihydrolipoate for up to 90 min and Cd2+ uptake as well as viability criteria were monitored. Both exposure regimens diminished Cd2+ uptake in correspondence to time and concentration. They also ameliorated Cd2(+)-induced cell deterioration as reflected by the decrease in Cd2(+)-induced membrane damage (leakage of aspartate aminotransferase), by the lessening of the Cd2(+)-stimulated lipid peroxidation (TBA-reactants) and by the increase in Cd2(+)-depleted cellular glutathione (GSH + 2 GSSG). Half-maximal protection was achieved at molar ratios of 9.9 to 19 (lipoate vs. Cd2+) and 0.25 to 0.74 (dihydrolipoate vs. Cd2+), indicating a 19.5 to 50.6 lower protective efficacy of lipoate as compared to dihydrolipoate. Lipoate induced an increase in extracellular acid-soluble thiols different from glutathione. It is suggested that dihydrolipoate primarily protects cells by extracellular chelation of Cd2+, whereas intracellular reduction of lipoate to the dihydro-compound followed by complexation of both intra- and extracellular Cd2+ contributes to the amelioration provided by lipoate.
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PMID:Studies on the efficacy of lipoate and dihydrolipoate in the alteration of cadmium2+ toxicity in isolated hepatocytes. 211 57

The effect of N-benzyl-D-glucamine dithiocarbamate (BGD) on the renal toxicity induced by acute exposure to cadmium-metallothionein (Cd-MT) in rats was studied. Rats were injected intraperitoneally with BGD (400 mumol/kg) 6, 12, or 24 h after intraperitoneal injection of Cd-MT (1.78 mumol Cd as Cd-MT/kg) and thereafter they received three injections of BGD (400 mumol/kg) daily for 3 days. Urinary protein concentration and aspartate aminotransferase (AST) activity significantly increased 1 day after Cd-MT treatment and decreased to control levels at 9 days after the treatment. Urinary excretion of glucose and amino acids rose gradually reaching maximum levels 5 days after Cd-MT treatment and returned to the control levels at 9 days. BGD injection significantly reduced the increases in the urinary excretion of protein, AST, glucose and amino acid, which were produced by Cd-MT treatment. Significant increases in urine volume were observed after Cd-MT treatment. BGD injection inhibited the increase in urine volume caused by Cd-MT treatment. A long time interval (12 and 24 h) between the administrations of Cd-MT and BGD resulted in a decreased protective effect of BGD against Cd-MT-induced renal damage. Following Cd-MT injection, the major route of excretion of cadmium (Cd) was via the urine and the kidney was the major site of accumulation of Cd. BGD injection remarkably increased the urinary excretion of Cd, resulting in a significant reduction in the kidney Cd concentration. The results of this study indicate that BGD injection is effective in decreasing the Cd concentration in the kidney, resulting in the protective effect on Cd-MT-induced renal damage.
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PMID:Effect of N-benzyl-D-glucamine dithiocarbamate on renal toxicity induced by cadmium-metallothionein in rats. 235 Feb 40

Recent work indicated that administration of the pyrimidine analog 5-azacytidine (AZA), either to cells in culture or to rats, results in an enhancement of expression of the metallothionein (MT) gene. Since MT is thought to play a central role in the detoxification of cadmium, the present study was designed to assess the effect of AZA pretreatment on cadmium cytotoxicity. Cultured rat liver cells (TRL 1215) in log phase of growth were first exposed to AZA (8 microM). Forty-eight hours later, cadmium (10 microM) was added. MT concentrations were then measured 24 hr after the addition of cadmium. A modest increase in MT amounts over control (1.7-fold) was detected after AZA treatment alone. Cadmium alone resulted in a 10-fold increase in MT concentrations. The combination of AZA pretreatment followed by cadmium exposure caused a 23-fold increase in MT concentrations over control. Treatment with the DNA synthesis inhibitor hydroxyurea (HU) eliminated the enhancing effect of AZA pretreatment on cadmium induction of MT, indicating that cell division is required. AZA-pretreated cells were also harvested and incubated in suspension with cadmium (250 microM, 37 degrees C) for 0 to 90 min. After incubation intracellular and extracellular fluids were separated by centrifugation through an oil layer. AZA-pretreated cells showed marked reductions in cadmium-induced cytotoxicity as reflected by reduced intracellular potassium loss, glutamic-oxaloacetic transaminase loss, and lipid peroxidation (assessed by thiobarbituric acid reactants) following cadmium exposure. AZA pretreatment had no effect on the cellular uptake of cadmium. Results suggest that AZA pretreatment induces tolerance to cadmium cytotoxicity which appears to be due to an increased capacity to synthesize MT rather than high quantities of preexisting MT at the time of cadmium exposure.
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PMID:Reduced cadmium-induced cytotoxicity in cultured liver cells following 5-azacytidine pretreatment. 241 62

The pyrimidine analog, 5-azacytidine (AZA-CR), has been shown to increase the expression of the metallothionein (MT) gene and to induce tolerance to cadmium toxicity. Since incorporation into DNA of AZA-CR appears to be required for this effect, the deoxynucleoside of AZA-CR should also be effective. Therefore, this study was undertaken to assess the effect of 5-aza-2'-deoxycytidine (AZA-CdR) pretreatment on cadmium-induced cytotoxicity and MT expression in cultured cells. TRL 1215 cells in log phase of growth were exposed to AZA-CdR (0.4, 0.8, 4.0, 8.0 microM) followed 48 h later by the addition of cadmium (10 microM). MT concentrations were measured 24 h after the addition of cadmium. AZA-CdR alone caused modest, dose-related increases in MT levels (2.3-fold maximum), while cadmium alone resulted in a 9.5-fold increase. Pretreatment with AZA-CdR in combination with cadmium caused a 19--24-fold increase in cellular MT at all doses of AZA-CdR. Addition of the DNA synthesis inhibitor, hydroxyurea (HU), to the incubation medium during AZA-CdR exposure prevented the enhancing effect of the analog on cadmium induction of MT accumulation. Time course studies revealed that AZA-CdR pretreatment reduced the time required for cadmium to induce MT levels from 4--8 h to 0--2 h. AZA-CdR pretreated cells placed in suspension with cadmium (125 microM) showed a marked reduction in cadmium-induced cytotoxicity as reflected by reduced glutamic-oxaloacetic transaminase (GOT) loss. Uptake studies showed that AZA-CdR pretreatment had no effect on cadmium transport during the initial phases of exposure, indicating that an alteration in the toxicokinetics of the metal did not account for the reduction in toxicity. AZA-CdR did, however, cause hypomethylation of the MT-I gene. These results suggest that AZA-CdR pretreatment induces tolerance to cadmium toxicity by increasing the genetic expression of MT possibly through hypomethylation of the MT gene.
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PMID:Increased metallothionein gene expression in 5-aza-2'-deoxycytidine-induced resistance to cadmium cytotoxicity. 245 60

The suitability of DL-alpha-lipoic acid (LA) to serve as an antidote in cadmium (Cd) toxicity in rat hepatocytes was investigated. Isolated hepatocytes were exposed to 200 and 450 microM Cd in the presence of 0.2, 1.0 and 5.0 mM LA, respectively. After 30 min of incubation various criteria of cell viability were monitored. Lipoic acid markedly diminished Cd uptake. Concomitantly, Cd-induced membrane injury, as reflected by the leakage of aspartate aminotransferase and sorbitol dehydrogenase (SDH) was decreased. Moreover, LA protected against intracellular toxic responses to Cd, such as a decrease in cellular SDH activity, a decrease in cellular acid soluble thiols, especially in total glutathione, a decrease in cellular urea and an increase in thiobarbituric acid (TBA) reactants, as a measure of lipid peroxidation. Most protective effects were seen in hepatocytes challenged with the lower Cd concentration and coincubated with 5 mM LA. In contrast, at 450 microM Cd even the highest LA concentration applied either did only reverse Cd-effects incompletely (SDH-response, TBA-reactants) or did not protect at all (Cd uptake, enzyme leakage, loss of glutathione). The data indicate that DL-alpha-lipoic acid serves as a protective tool against Cd-induced membrane damage and cell dysfunction in hepatocytes. This stands as long as Cd exposure is low enough to permit interaction with LA prior to interaction with cell structures.
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PMID:Protective effects of DL-alpha-lipoic acid on cadmium-induced deterioration of rat hepatocytes. 250 68

Studies were carried out on the effect of various cadmium doses, which were given to growing rats in diet. A 42-day biological experiment was carried out on male growing Wistar rats. The animals divided into groups were given diets containing cadmium in amounts of 50, 100 and 200 ppm and diet with no adding cadmium. The diets contained 20% of protein in equal amounts from wheat gluten and casein. It was demonstrated that cadmium had a significant influence on diet intake and growth of rats. The absorption from diets containing 50, 100 and 200 ppm of cadmium was about 30 to 48%. The more cadmium was absorbed, the most was in blood and rat liver. Anaemia was noted in animals, which were given diets with cadmium. Rats had a low level of haematocrit and haemoglobin in plasma. It was shown that cadmium intake caused a significant decrease in plasma albumin concentration and increase of plasma alanine aminotransferase and aspartate aminotransferase activity.
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PMID:[Effect of various cadmium doses in the diet on the body of growing rats]. 263 83

The purpose of the study was assessment of the effect of an environment contaminated with heavy metals on the activity of certain enzymes of mixed saliva. The activity was determined of total acid phosphatase and phosphatase resistant to tartrate and formaldehyde, alkaline phosphatase, alanine and aspartate aminotransferase, and alpha-amylase. The studied material comprised 110 saliva samples obtained from three groups of children aged 8 years. Group I of 21 children lived in Szopienice, group II of 30 children lived in Miasteczko Slaskie. In both these localities the children were exposed to mean daily concentrations, above the permitted ones, mainly of lead compounds, in lower degree to cadmium and zinc compounds. Environment contamination in Szopienice was greater than in Miasteczko Slaskie. Group III of 59 children living in Lubowice served as controls. In that town the permissible concentrations of these compounds were not exceeded. Statistical analysis of these results showed that the activity of total acid phosphatase in groups I and II, that is in the contaminated areas, was highly significantly greater than in the control group. The activity of alkaline phosphatase was raised only in the saliva in group I. No differences were found in the activity of alpha-amylase and aminotransferases.
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PMID:[Activity of certain salivary enzymes in school children exposed to excessive concentrations of lead and cadmium]. 264 Jun 43


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