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)

Enzyme activity modulation by cadmium in the liver of the teleost fish Sparus aurata was investigated in vivo following 3 and 6 days of CdCl2 administration (2.5 mg/kg body wt). The specific activities of the mitochondrial enzymes NAD-isocitrate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase were stimulated by approximately 20% after 3 days administration and were further increased (by about 40%) after 6 days treatment. In comparison with these enzymes, the activities of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT) in mitochondria were less stimulated after the two indicated intervals of treatment. Cadmium significantly reduced the activities of liver cytoplasmic GOT and GPT while a simultaneous increase occurred in the serum activities of these same enzymes. The activity of liver NADPH-cytochrome P450 reductase was stimulated by 25 and 40% after 3 and 6 days cadmium intoxication, respectively. Lastly, the antioxidant enzymes glutathione peroxidase and glutathione reductase in liver and catalase in both liver and blood were strongly reduced after 3 and 6 days cadmium administration. These data suggest that cadmium in fish hepatocytes alters cell membrane structure and concomitantly induces some perturbation in the integrity of the mitochondrial membrane.
 ...
PMID:Changes in liver enzyme activity in the teleost Sparus aurata in response to cadmium intoxication. 1033 Mar 29

Adult male rats were injected sc with cadmium chloride (CdCl(2)) in a single dose of 7 mg/kg body wt. Twenty-four hours postinjection, exposure to CdCl(2) increased the hemoglobin absorbance of the testes from 0.36 +/- 0.01 to 2.46 +/- 0.02. Pretreatment of rats with chlorpromazine (CPZ) 3 mg/kg ip either for 1 or 2 days before exposure to CdCl(2) significantly (p < 0.05) reduced the testicular damage and the hemoglobin absorbance decreased to 1.03 +/- 0.02 and 0.92 +/- 0.04, respectively. After CdCl(2) injection there was a progressive increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. CdCl(2) injection induced hemorrhage and a diffuse area of coagulative necrosis in liver. Pretreatment with CPZ partially protected liver from the effect of CdCl(2). Two months postinjection, exposure to CdCl(2) significantly decreased the weights of testes, epididymis, and accessory sex organs. Furthermore, CdCl(2) induced a highly significant (p < 0.01) decrease in sperm cell concentration and the percentage of mobile cells. Moreover CdCl(2) induced degenerative changes in testes, epididymis, and seminal vesicles. Pretreatment with CPZ partially protected these organs from the toxic effects of CdCl(2). It could be concluded that chlorpromazine partially antagonized the toxic effects of cadmium on liver, testes, and other male reproductive organs of rats.
 ...
PMID:The antagonistic effect of chlorpromazine on cadmium toxicity. 1055 21

The influence of aging on the sensitivity of the liver to the acute toxicity of cadmium has not been studied previously in adult rats. In this study hepatotoxicity caused by a single sc injection of CdCl(2) was compared in 5-, 18-, and 28-month-old male Fischer 344 rats. Doses of Cd were adjusted on the basis of the mean lean body mass for each age group of rats, and liver injury was evaluated 24 h after treatment. Cd treatment produced substantial increases in serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities in 5- and 18-month-old rats, whereas no significant increases were observed in 28-month-old rats. Histologic examination of representative livers from each age group confirmed the findings for serum enzyme activity; hepatocellular necrosis was observed only in livers from 5- and 18-month-old rats. The attenuation of Cd hepatotoxicity in senescent rats did not appear to be related to pretreatment levels of metallothionein or glutathione. Likewise, resistance to Cd could not be explained on the basis of metallothionein induction, which decreased as a function of aging. Thus, the mechanisms that account for the postmaturational decline in sensitivity to Cd do not appear to be associated with alterations in levels of the major factors that protect against Cd-induced hepatotoxicity.
 ...
PMID:Attenuation of cadmium-induced liver injury in senescent male fischer 344 rats: role of metallothionein and glutathione. 1062 Apr 79

It is reported repeatedly that severe hepatocellular necrosis along with infiltration of neutrophils occurs after acute cadmium exposure. Neutrophils, which migrate by the gradient of chemoattractants such as interleukin-8, are believed to play an important role in inflammation at the damaged sites. To investigate whether neutrophils aggravate or repair the liver injury induced by cadmium, we checked the hepatotoxic effects of cadmium on human interleukin-8 transgenic mice (hIL-8Tg), which overexpressed IL-8 and displayed an inability of neutrophil migration resulting from both the lack of chemotactic gradient and the downregulation of l-selectin on the surface of neutrophils. A significantly lower survival rate was observed in hIL-8Tg compared with wild-type mice after subcutaneous administration of cadmium. Evident liver injury characterized by abrupt increases in plasma GOT and GPT levels was found in hIL-8Tg at 18 h after cadmium administration. Histological examinations, including H & E staining and esterase staining, revealed the infiltration of numerous neutrophils into the damaged liver tissues in wild-type mice, and the inhibition of the neutrophil migration into the liver as well as enhanced hepatocellular necrosis in hIL-8Tg. Peripheral white blood cell and polymorphonuclear cell counts increased and reached their peaks at 12 h after cadmium administration in wild-type mice, whereas the increase in blood leukocyte counts was delayed in hIL-8Tg. There was no significant difference in the amounts of cadmium accumulated in liver and kidneys between wild-type mice and hIL-8Tg. In conclusion, an acute cadmium hepatotoxic effect was exacerbated in hIL-8Tg resulting from inhibited neutrophil migration, suggesting that migrated neutrophils can prevent aggravation of liver injury by acute cadmium administration.
 ...
PMID:Cadmium-induced acute hepatic injury is exacerbated in human interleukin-8 transgenic mice. 1070 62

To investigate the importance of the cadmium (Cd) exposure condition in the evaluation of toxic effect on renal function and bone metabolism, six groups of Male Wistar rats were given Cd at respective daily doses of 2, 5, 10, 20, 30 and 60 mgCd/kg (as CdCl2) via a gastric tube for 6 consecutive days a week for 60 weeks. In the groups given a low Cd dose (2, 5 and 10 mgCd/kg), relatively more Cd accumulated in the kidney without liver damage than in the liver. In the high Cd dose groups (20, 30 and 60 mgCd/kg), on the other hand, more Cd accumulated in the liver than in the kidney. The daily intake of Cd dose from the intestinal tract in each experimental group was deduced to be about 0.36%-0.54% of the cumulative dose of oral Cd administration. The daily intake of Cd into the body was estimated as 7, 22, 40, 100, 120, 260 microgCd/kg/day in the experimental groups of 2, 5, 10, 20, 30 and 60 mgCd/kg/day, respectively. Increase of plasma enzyme activity (GOT, GPT) and of urinary enzyme excretion (NAG, AAP, GST), reflecting hepatic damage and renal dysfunction, was found in the high Cd dose groups (30 and 60 mgCd/kg) from the 5th week. Non-CdMT concentration in the kidney was also significantly high in the high Cd dose groups. In the low Cd dose groups (2 and 5 mgCd/kg), although the renal Cd concentration was higher than that of the high Cd dose groups, prominent renal dysfunction and hepatic damage were not observed. Regeneration, vacuolization, and eosinophilic bodies in proximal tubular tissue were mainly observed in the groups subjected to 20, 30 and 60 mgCd/kg administration. Very slight regeneration was also observed in the renal proximal tubular tissue at the 30th week for the 5 mgCd/kg and 10 mgCd/kg groups, and at the 60th week for the 2 mgCd/kg group. Remarkable decrease of bone mineral density at the midpoint of the femur was found in the high Cd dose groups. Also, the decrease in bone mineral density was observed before or after the manifestation of the renal dysfunction, depending on the dose and the duration of Cd administration. Urinary excretion of Pyr, DPyr, and Ca increased and plasma BGP decreased in the higher Cd dose groups. Osteoid volume in the femur tissue was not increased significantly by Cd exposure. Based on these results, it was suggested that Cd exposure caused osteoporotic change. The results of the present study suggested that the toxic effect of Cd on renal function and that on bone metabolism were caused at different times and that renal Cd concentration after long-term oral Cd administration depended on the dose and the duration of Cd exposure.
 ...
PMID:Relationship between renal dysfunction and bone metabolism disorder in male rats after long-term oral quantitative cadmium administration. 1106 77

The levels of plasma nitric oxide (NO), endothelin-1 (ET-1) and ALT in the patients with chronic hepatitis B and active cirrhosis and the correlation among them were observed and analyzed. NO3- was restored by using cadmium column assay and NO2- measured by heavy nitrogen assay. The primitive NO3- and total restored NO2- (NO3-/NO2-) in plasma of the patients with chronic hepatitis and cirrhosis. Plasma ET-1 and ALT levels were determined by using radioimmunological assay and Lai's assay, respectively. Compared with normal control group, the plasma levels of NO2-/NO2- and ET-1 in the patients with chronic active hepatitis and active cirrhosis were significantly increased (P < 0.05-0.01). There was a positive correlation between NO and ALT, and ET-1 and ALT in the patients with chronic active hepatitis and active cirrhosis respectively. It was suggested that elevation of both NO and ET-1 levels were closely related with injury severity of liver function.
 ...
PMID:Study on the correlation of plasma NO, ET-1 and ALT in the patients with chronic hepatitis and cirrhosis. 1121 47

Stress responses and changes in protein metabolism were studied in common carp Cyprinus carpio exposed to 0, 0.8, 4, and 20 microM cadmium (Cd) over a 29-day period. Blood and other tissue samples were taken after 4 and 29 days of exposure. The highest Cd concentration proved to be lethal to the fish, resulting in 100% mortality after 21 days of exposure. Cd accumulated in the tissues in the following order: kidney>liver>gills. Blood hematocrit, blood hemoglobin, plasma glucose, plasma lactate, and tissue total protein contents were not significantly altered. The concentrations of Cd and zinc (Zn) binding metallothioneins ((Cd, Zn)-MTs) were in the following order=liver>kidney>gills. An increase in (Cd, Zn)-MTs was observed at all exposure concentrations at days 4 and 29 in kidney and at Day 29 in gills. No significant changes in (Cd, Zn)-MT contents were found in liver. The concentrations of free amino acids and the activities of proteases were increased at Day 4 in gills, liver, and kidney of carp exposed to 4 and 20 microM Cd, and in gills and kidney at Day 29 in carp exposed to 4 microM Cd. The observed increases in the activities of aspartate aminotransferase and alanine aminotransferase suggest that the observed proteolysis is intended to increase the role of proteins in the energy production during Cd stress. However, this increased activity of both aminotransferases was not found in gills during exposure to the lethal Cd concentration, indicating that Cd may also cause an inhibitory effect on the activity of these enzymes above a certain level.
 ...
PMID:Stress responses and changes in protein metabolism in carp Cyprinus carpio during cadmium exposure. 1122 34

In vitro study for the determination of the toxicity of some pesticides (glyphospate and paraquat) and cadmium chloride (CdCl2) on the activities of serum acetylcholinesterase (AChE), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AlP), and acid phosphatase (AcP) is described. Changes in electrophoretic patterns of serum proteins were also tested. Results revealed that glyphosate was effective on all enzymes except AcP. Its IC50 values (the concentration of compound that inhibits 50% of the enzyme activity in 1 h at 37 degrees C) were 714.3, 750, 54.2, 270.8, and 71.4 mM for AChE, LDH, AST, ALT, and AlP, respectively. The inhibitory effect of paraquat varied markedly among all enzymes. The IC50 values of paraquat were 321.4 and 750 mM for AST and ALT, respectively. It had mild effect on AChE and LDH; and no effect on the activities of AlP and AcP. The effect of CdCl2 was pronounced with AChE, ALT, AlP, and AcP, and no effect on LDH and AST was found. The corresponding IC50 values were 77.7, 22.2, 33.3, and 83.3 mM for AChE, ALT, AlP, and AcP, respectively. Polyacrylamide gel electrophoretic patterns of serum proteins showed marked differences with glyphosate and CdCl2 but not with paraquat. The results suggest that the in vitro enzyme-activity test seems to have a potential for the assessment of pesticide and heavy metal toxicity.
 ...
PMID:Influence of paraquat, glyphosate, and cadmium on the activity of some serum enzymes and protein electrophoretic behavior (in vitro). 1128 Dec 53

Four groups of goldfish were exposed to cadmium in a concentration of 20 mg Cd/l water under aquarium conditions. The duration of exposure was 1, 4, 7 and 15 days. It was shown that the activity of superoxide dismutase (SOD) in the red blood cells (RBC) significantly decreased after the first day of cadmium exposure. However, the SOD activity increased after 7 and 15 days of cadmium treatment. Elevated activity of catalase (CAT) was found in erythrocytes of cadmium-treated fishes after 15 days, whereas plasma GOT levels was increased after 7 and 15 days and GPT levels after 1, 4, 7 and 15 days of cadmium treatment. This was accompanied by a significant decrease of blood hemoglobin concentrations (after 15 days) and hematocrit values (after 7 and 15 days). However, the concentration of blood glucose significantly increased after 1, 4, 7 and 15 days of cadmium exposure. These results indicate that cadmium causes oxidative stress and tissue damage in the exposed fishes.
 ...
PMID:Activities of superoxide dismutase and catalase in erythrocytes and plasma transaminases of goldfish (Carassius auratus gibelio Bloch.) exposed to cadmium. 1130 Feb 21

Several observations, both in humans and laboratory animals, have suggested that proanthocyanidins exhibit a broad spectrum of pharmacological, therapeutic and chemoprotective properties. Specifically, some of our earlier studies have shown that IH636 grape seed proanthocyanidin extract (GSPE, commercially known as ActiVin) provides excellent concentration- and dose-dependent protection against toxicities induced by diverse agents, such as acetaminophen, hydrogen peroxide, 12-O-tetradecanoylphorbol-13-acetate (TPA), smokeless-tobacco extract, idarubicin and 4-hydroxyperoxycyclophosphamide in both in vitro and in vivo models. In some models, GSPE proved to be a better cytoprotectant than vitamins C, E and beta-carotene. The purpose of this investigation was three fold: (i) to indirectly assess the bioavailability of GSPE in multiple target organs, (ii) quantify GSPE's capacity to avert cadmium chloride (CdCl2)-induced nephrotoxicity, dimethylnitrosamine (DMN)-induced splenotoxicity and O-ethyl-S,S-dipropyl phosphorodithioate (MOCAP)-induced neurotoxicity, and lastly (iii) to evaluate possible mechanisms of protection in mice. In order to determine all these, three separate experiments were designed and each experiment consisted of four groups, such as vehicle control, GSPE alone, toxicant alone and GSPE + toxicant. GSPE was administered orally (100 mg/Kg) for 7-8 days prior to the toxicant exposure. Parameters of the analyses included evaluation of serum chemistry changes (ALT, BUN and CK), histopathology and integrity of genomic DNA, both quantitatively and qualitatively. Results indicate that GSPE preexposure prior to cadmium chloride and DMN provided near complete protection in terms of serum chemistry changes (ALT, BUN and CK) and inhibition of both forms of cell death. e.g., apoptosis and necrosis. DNA damage, a common denominator usually associated with both apoptosis and necrosis was significantly reduced by GSPE treatment. Histopathological examination of organs correlated strongly with the changes in serum chemistry and the DNA modification data. Surprisingly, MOCAP exposure showed symptoms of neurotoxicity coupled with serum chemistry changes in the absence of any significant genomic DNA damage or brain pathology. Although, GSPE appeared to partially protect the neural tissue, it powerfully antagonized MOCAP-induced mortality. Taken together, this study suggests that in vivo GSPE-preexposure may protect multiple target organs from a variety of toxic assaults induced by diverse chemical entities.
 ...
PMID:Unique organoprotective properties of a novel IH636 grape seed proanthocyanidin extract on cadmium chloride-induced nephrotoxicity, dimethylnitrosamine (DMN)-induced splenotoxicity and mocap-induced neurotoxicity in mice. 1133 61


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>