Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the influence of hepatic metallothionein (MT) on the hepatotoxic response to carbon tetrachloride (CCl4), adult male rats were pretreated with a 10 mg X kg-1 dose of zinc (Zn) 24 h prior to CCl4 (i.p., l mL X kg-1) treatment. Zn pretreatment increased the hepatic MT concentrations markedly and reduced the magnitudes of the CCl4-induced reduction of cytochrome P450 concentration as well as elevation of serum alanine aminotransferase and aspartate aminotransferase activities when determined at 4 or 24 h following CCl4 treatment. Treatment of Zn-exposed animals with CCl4 also resulted in significant reduction of the concentrations of hepatic MT (as determined by the cadmium-saturation method) as well as cytosolic Zn. Sephadex G-75 chromatographic study of hepatic cytosols showed that MT-bound Zn was selectively depleted by CCl4 exposure. Moreover, it was demonstrated that CCl4, after metabolic activation, reduced the cadmium binding capacity of Zn-induced hepatic MT in vitro. To examine the possible protective effect of Zn independent of induction of MT synthesis, CCl4 was administered 2 h following Zn pretreatment and the hepatotoxic response was examined 4 h later. This study revealed limited protection by Zn prior to the induction of MT synthesis. These data further support a role of MT in the modulation of CCl4 hepatotoxicity.
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PMID:Interaction of metallothionein and carbon tetrachloride on the protective effect of zinc on hepatotoxicity. 379 Oct 46

Cadmium effects on the bluegill sunfish (Lepomis macrochirus) were assessed histologically and biochemically and the effects were compared with effects on the ecologically relevant parameters of growth and survival. Growth and survival were monitored and tissues were removed for histopathological assessment of toxicant effects in a 163-day chronic exposure. The biochemical effects of cadmium were determined in a 32-day subchronic exposure. Exposure of fish to cadmium in hard water (363 mg Cd/liter) caused significant reductions in growth at 3.9 and 12.7 mg Cd/liter. Mortality was significantly increased over controls at 12.7 mg Cd/liter. Histopathological lesions were observed in gill tissue from fish exposed to 3.9 and 12.7 mg Cd/liter at all times during the chronic exposure. No histopathological lesions were observed in any internal organ during this exposure. In a 32-day subchronic exposure, cadmium caused significant increases in serum acid phosphatase and N-acetyl-beta-d-glucosaminidase activities. Serum aspartate and alanine transaminase and lactate dehydrogenase activities were not increased by cadmium exposure. Liver lysosomal membranes were destabilized by cadmium exposure. This indicates an alteration in lysosome function. The utility of biochemical and histological procedures for estimating safe concentrations of environmental pollutants are discussed.
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PMID:The histological and biochemical effects of cadmium exposure in the bluegill sunfish (Lepomis macrochirus). 395 30

Two serum enzymes which originate from the liver under different circumstances were examined as potential biological indicators in serum for cadmium toxicity. The first of those is an enzyme that leaks from damaged liver cells. The second is an enzyme that is secreted by the normal functioning liver. Cadmium chloride was injected s.c. into male and female rats of the Wistar strain (8, 15 and 22 weeks old), at doses of 1.0, 1.5 and 2.0 mg Cd/kg body weight (in total 18 groups). Cholinesterase (CHE; EC 3.1.1.8) activity in serum was found to decrease with time after the administration of a single injection of cadmium chloride and, in all experimental groups, was significantly lower than the control values on day 2 after the injection. Glutamic pyruvic transaminase (GPT; EC 2.6.1.2) activity in serum, however, increased only in the oldest group of males receiving the high dose levels of cadmium. A time-course experiment in which male and female rats 15 weeks of age were administered 1.5 mg Cd/kg body weight showed that the serum CHE activity started to decrease on day 1 after the injection, attained the lowest level on days 2 and 3, and then recovered almost to control levels on day 5. On the other hand, the GPT activity remained at or less than control values throughout the experimental period. The results indicate that CHE activity in serum is a sensitive biological indicator for cadmium toxicity.
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PMID:Depression of serum cholinesterase activity by cadmium. 404 26

Resistance to the lethal action of Cd2+ produced in mice was maintained for 6 to 24 hr after pretreatment with 1/10 of the challenge Cd2+ doses as shown by an increased oral LD50. Pretreatment 24 hr prior to the challenge doses was most effective. In addition, 1/20 to 1/7 of the challenge doses was necessary to acquire the tolerance to the acute oral toxicity of Cd2+. The largest effect was found for pretreatment with 1/7 of the challenge doses. Acute liver injury at 24 hr after challenge with a large dose of Cd2+ (100 mg Cd2+/kg, p.o.) was markedly reduced by pretreatment with a small dose of the cation (15 mg Cd2+/kg, p.o.) 24 or 48 hr prior to the challenge dose as shown by a marked reduction in serum GOT and GPT activities and the reversal of histopathological changes. The elevated serum urea nitrogen at 4 hr after the Cd2+ challenge was reduced by pretreatment 6 to 24 hr prior to the challenge dose. In spite of the increased urea nitrogen 4 hr after the Cd2+ challenge, no morphological alterations were observed in the kidney at 24 hr. Serum Alp activity was not significantly influenced by the Cd2+ challenge. Glucose in serum was increased by the administration of a small dose of Cd2+, but was unaffected by a large dose. Decreases in hepatic RNA and DNA concentrations at 24 hr after the Cd2+ challenge were prevented by pretreatment 24 or 48 hr prior to the challenge dose. Potentiation of hexobarbital sleep time was observed at 6 or 24 hr after a small dose of Cd2+. Nevertheless, further potentiation at 24 hr after the Cd2+ challenge (75 mg Cd2+/kg, p.o., in this case) was reduced by pretreatment 24 hr prior to the challenge dose. A major target organ for the acute oral toxicity of Cd2+ was the liver rather than the kidney.
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PMID:Defense mechanisms against cadmium toxicity I. A biochemical and histological study of the effects of pretreatment with cadmium on the acute oral toxicity of cadmium in mice. 620 99

The effect of a single intravenous (i.v.) injection of cadmium nitrate was investigated in livers of male Wistar rats. A significant increase in liver weight, accompanied by an elevation of total hepatic DNA content was observed. DNA synthesis as measured by the incorporation of [3H]thymidine, was found to be 6 times greater than the control, at 24 h after treatment, and remained elevated over a period of 72 h. This elevation in DNA synthesis was not a consequence of cell necrosis, since no increase of serum glutamate-pyruvate transaminase (SGPT) activity was observed.
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PMID:Stimulation of DNA synthesis after a single administration of cadmium nitrate. 652 20

Pretreatment with nickel has earlier been shown to protect against cadmium intoxication. The effect of cadmium pretreatment on the nephro- and hepatotoxicity of nickel has been investigated. The administration of cadmium (6 mg/kg, i.m., once) to rats significantly enhanced urinary excretion of ALP, LDH, GOT, amino acids and proteins and increased the activity of serum ALP, GOT, and GPT, while the administration of nickel (6 mg/kg, i.p., 3 days) altered these parameters less significantly. These changes in urine and serum were used as a measure of renal and hepatic damage. The administration of nickel for three days, one week after cadmium treatment, caused significantly more marked enzymuria, aminoaciduria, proteinuria and an increase in the activity of serum enzymes than induced by either of them individually. However, cadmium pretreatment had no influence on urinary excretion or hepatic uptake of nickel, but increased renal uptake of nickel on the fourth day. The results suggest that cadmium enhances the nephro- and hepatotoxicity of nickel.
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PMID:Effect of cadmium pretreatment on nickel toxicity. 653 85

Rats were administered ferrous sulfate, cadmium chloride, or sodium vanadate alone and in combination with carbon tetrachloride (CCl4) to determine if lipid peroxidation is associated with the toxicity of the three metals and to determine if there is an interaction between these metals and CCl4 in producing lipid peroxidation and hepatotoxicity. Expired ethane was used as an index of lipid peroxidation while serum alanine aminotransferase (ALT) and histopathology were used to assess liver damage. Lipid peroxidation did not appear to be associated with the hepatotoxicity of cadmium since no measurable increase in ethane production was observed when serum ALT concentrations were doubled relative to controls. Cadmium did not increase ethane when administered with CCl4 and the increase in ALT was additive. Iron and vanadate produced small significant increases in ethane production but no increase in ALT and only minor histopathologic changes, yet potentiated lipid peroxidation and liver damage when administered with CCl4. Thus, Cd did not produce lipid peroxidation and did not potentiate the lipid peroxidation and hepatotoxicity of CCl4, while iron or vanadate which produced lipid peroxidation alone potentiated the lipid peroxidation and hepatotoxicity of CCl4.
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PMID:Interaction of metals and carbon tetrachloride on lipid peroxidation and hepatotoxicity. 655 84

Twenty-one male rabbits were divided into three groups: rabbits of two groups were given pelleted food containing cadmium chloride at a dose level of 300 micrograms Cd/g over periods of 44 or 19 weeks. Rabbits of the last group were given ordinary commercial pelleted food and served as controls. Cadmium increased urinary protein and amino acid by week 19 and increased it to a remarkably high level by week 44. After cessation of cadmium exposure, rabbits of the first group (44 weeks exposure group) showed only little recovery from cadmium health effects: proteinuria and aminoaciduria were slightly improved. Depressed hepatic functions were also slightly improved, but did not return to the control level in 24 weeks. Fat and bone metabolism also remained depressed below the control level. Anemia did not also readily recover. On the other hand, rabbits of the second group (19 weeks exposure) recovered from the effects of cadmium: proteinuria and aminoaciduria in most animals disappeared soon after the end of cadmium exposure, plasma GPT fell after 1 week, and hemoglobin and hematocrit returned to normal in 6-11 weeks. The above results show that after cessation of cadmium exposure, mild cadmium-induced health effects were reversible in a short period, while more severe effects were not readily reversible. High performance liquid chromatographic (HPLC) profiles of renal and hepatic cadmium-thionein (Cd-MT) during and after exposure to cadmium showed no correlation to the degree of cadmium health effects, and therefore, did not help to elucidate mechanisms of the recovery from cadmium-induced health effects, probably because cadmium not bound with metallothionein (non-MT-Cd) is responsible for inducing renal effects.
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PMID:Reversibility of cadmium-induced health effects in rabbits. 673 56

The role of zinc (Zn) in preventing cadmium (Cd)-induced alterations of liver function and carbohydrate metabolism was studied in female rats. The animals were divided into four groups. To the diet for Group I was added 200 micrograms Cd/g of diet, to that for Group II was added 200 micrograms Zn/g of diet, and to that for Group III were added 200 micrograms Cd/g and 200 micrograms Zn/g of diet. Group IV was the control group fed normal diet. At the 11th, 26th, and 40th week of exposure, one-third of each group of animals were sacrificed and serum GPT and ALP activities, and glucose and insulin levels were measured. At the 26th and 40th week, serum GPT activity of Group I was significantly higher compared with those of Groups III and IV, and the serum glucose value of Group I was lower than that of Group III. At the 40th week, the serum insulin value of Group I was significantly higher than that of Group III. From these results, it is suggested that orally administered Zn prevents Cd-induced alterations of liver functions and the regulation of blood glucose in rats.
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PMID:Effects of zinc on cadmium-induced alterations in hepatic functions and blood glucose of rats. 683 6

The toxic effects of cadmium (Cd) and mercury (Hg), as chloride salts, were studied using an hepatic human fetal cell line (WRL-68 cells). From viability curves and the proliferative capacity of the cell in the presence of the metal, three different cell treatments were chosen, (1) 0.5 microM of the metal chloride for 24 h (acute low dose treatment), (2) 0.5 microM of the metal chloride for 7 days (chronic treatment), and (3) 5 microM of the metal chloride for 24 h (acute high dose treatment). WRL-68 cells grown in the presence of Cd exhibited the same proliferative curve as control cells, whereas in the case of Hg, the cells increased their proliferative capacity. Both metals produced ultrastructural alterations in different degrees, mainly observed as mitochondrial and RER structural changes, depending of the treatment and concentration of the metal used. Cytotoxicity was assessed by measuring the release of lactate dehydrogenase from the cells. Acutely high dose-treated cells showed the highest value for this parameter, and Cd-treated cells presented higher lactate dehydrogenase release than the Hg-treated ones. Cell damage was also measured by alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) activities. Acute high dose Cd treatment caused the highest value of enzymatic release. Lipid peroxidation was significantly different with respect to control cells in chronic and acute high dose treatments with both metals. Metallothionein (MT) induction in response to Hg treatment was not detected. However, a dramatic induction of this protein occurred in Cd-treated cells. WRL-68 cells differentially respond to Cd and Hg making this hepatic fetal human cell line a useful tool in investigating the mechanism of toxicity of these heavy metals.
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PMID:Cadmium and mercury toxicity in a human fetal hepatic cell line (WRL-68 cells). 748 68


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