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:2.6.1.2 (alanine aminotransferase)
26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to evaluate how well the development of CCl4 hepatotoxicity in vivo can be modeled in primary cultures of rat hepatocytes, biochemical alterations were determined in liver samples from rats given CCl4 and in liver cells cultured for 18 hr then exposed to CCl4. Soluble thiol levels matched closely between tissue and hepatocytes (11 vs 12 micrograms-SH/mg protein) prior to exposure. Comparable concentrations of CCl4 were measured in blood (0.30 mM at 30 min) and in culture medium (0.49 mM at 5 min). Simultaneous inhibition of the endoplasmic reticulum calcium pump and stimulation of phosphorylase a activity occurred at early times in vivo (30 min) and in vitro (5 min). Glucose-6-phosphatase was inhibited next in liver (120 min) and in cells (20 min). 5'-Nucleotidase was not affected at any time points examined in either system. Leakage of glutamic-pyruvic transaminase and depletion of glycogen were maximal at later times in vivo (greater than or equal to 8 hr) and in cells (30 min). Total calcium content was increased severalfold in liver tissue (24 hr), but was not elevated in hepatocytes. This lack of calcium accumulation in cells appeared to result from impaired mitochondrial calcium uptake. Thus CCl4-induced biochemical changes followed nearly the same continuum in both models, although the progression was much more rapid in vitro than in vivo.
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PMID:Biochemical evaluation of rat hepatocyte primary cultures as a model for carbon tetrachloride hepatotoxicity: comparative studies in vivo and in vitro. 296 7

Indomethacin was parenterally administered (6 mg/Kg/day) for 30 days to rabbits, to evaluate changes in serum biochemical parameters and any ultrastructural alterations induced by the drug at the hepatic level. An analysis of the results demonstrated that when the group of rabbits, a statistically significant increase in the serum ALT was found in the treated rabbits. Ultrastructural observations showed the following hepatocyte alterations: 1) minimum mitochondrial alterations 2) mild signs of cholestasis (pericanalicular osmophilic bodies) 3) Smooth endoplasmic reticulum hyperplasia. These findings suggest that indomethacin has the capacity to induce hepatic lesions in the rabbit and this is probably due to the surfactant mechanism.
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PMID:Hepatic alterations in indomethacin-treated rabbits. 340 44

The hepatotoxicity of atrazine was investigated by studying clinical parameters related to hepatic function and by electron microscopy. Three groups to male albino rats (Wistar strain) received 100, 200 and 400 mg of atrazine/per kg of body weight/per day, for 14 days. One group received 600 mg atrazine/per kg of body weight/per day, for 7 days. At termination of dosing, the animals were sacrificed and blood was drawn for the determination of serum total lipids, glucose, alanine aminotransferase (ALT) and alkaline phosphatase (SAP). A dose dependent decrease in serum glucose concentration was observed in all the groups. In contrast, a dose relate increase in total serum lipids, was apparent at all dose levels studied. Activity of serum ALT and SAP increased approximately 60% and 200% respectively in rats given 600 mg atrazine/kg bw for 7 days. The liver was examined grossly and microscopically. Electron microscopy disclosed no changes in the hepatocytes of rats treated with the low dose (100 mg/kg bw). At high doses, electron microscopy revealed hepatocytic proliferation and degeneration of smooth endoplasmic reticulum, lipid accumulation and alteration of bile canaliculi proportional to dose and duration of treatment.
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PMID:Hepatotoxicity induced by the herbicide atrazine in the rat. 342 62

A hepatitis B surface antigen (HBsAg) chronic carrier chimpanzee experimentally superinfected with delta virus (DV) developed chronic DV infection. Over a period of 12 months, serologic and biochemical changes were correlated with morphologic abnormalities of the liver. Severe hepatic necrosis and inflammation accompanied the initial acute episode of hepatitis on Day 35 after inoculation, followed by complete resolution of these lesions over the next 3 months. A second episode of hepatitis occurred on Day 145, and severe necrosis and inflammation recurred along with the reappearance of delta antigen in the hepatocytes. Delta antigen persisted in the liver following the second episode of hepatitis and has remained positive throughout the observation period of 1 year. During the initial acute episode, the hepatocytes exhibited foamy cytoplasmic changes resembling microvesicular fat. However, ultrastructural studies of the same cells revealed only vacuolization of the cytoplasm without evidence of fat droplets. The inflammatory infiltrate during both episodes of hepatitis demonstrated a striking predominance of macrophages over lymphocytes. Hepatocyte abnormalities observed by electron microscopy included vacuoles, proliferated endoplasmic reticulum, and tubules similar to those seen in posttransfusion non-A, non-B hepatitis. However, the tubular and reticular abnormalities coincided with delta antigen expression in liver biopsies detected by direct immunoperoxidase staining and abnormal alanine aminotransferase levels in the serum, which suggests a possible causal relationship. Nuclear abnormalities were not seen.
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PMID:Pathologic and ultrastructural changes of acute and chronic delta hepatitis in an experimentally infected chimpanzee. 351 26

Murine IFN(gamma) and human IFN(alpha)-AD:Bgl were compared over a limited dose range and after single and multiple dosing for their effect on male mouse liver oxidative and conjugative drug metabolizing enzymes. Both IFNs depressed the microsomal cytochrome P-450 concentration but did not alter cytosolic glutathione S-transferase nor microsomal UDP-glucuronosyltransferase activity. Both IFNs showed some slight hepatotoxicity (elevated serum ALT), alpha AD:Bgl more than gamma, especially after multiple dosing. While the IFNs did not produce significant increases in liver weight, they did increase the yield of microsomal protein. The increased endoplasmic reticulum may compensate for the decreased cytochrome P-450 concentration and so account for the lack of observed effect of the IFNs on hexobarbital sleep times in vivo. Overall, the minimal effects of murine gamma-IFN on the mouse liver were no different than those of human alpha AD:Bgl.
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PMID:Effect of murine gamma-interferon on the mouse liver and its drug-metabolizing enzymes: comparison with human hybrid alpha-interferon. 392 33

Male Wistar rats were exposed (six hours/day, five days/week) to 0, 50, 300 or 600 p.p.m. of ethylbenzene vapour in the air, and killed after 2, 5, 9 or 16 weeks of exposure. After 600 p.p.m., liver-microsomal protein but not cytochrome P-450 concn. was slightly increased; NADPH-cytochrome c reductase was increased maximally by 30% (1.3-fold), 7-ethoxycoumarin O-deethylase (1.8-fold) and UDPG-transferase (2.3-fold). The increase in liver-cytosolic D-glucuronolactone dehydrogenase paralleled the glucuronidation activity (less than or equal to 2-fold). In the kidneys, only 7-ethoxycoumarin O-deethylase (less than or equal to 3.5-fold) and UDPG-transferase (less than or equal to 1.8-fold) showed dose-related increases. Ethylbenzene exposure did not deplete hepatic glutathione (GSH); kidney GSH was slightly increased (less than or equal to 1.3-fold) according to dose. Urine excretion of thioethers was increased with dose, and at 600 p.p.m. was eight times control levels. At 600 p.p.m. there was no increase in serum alanine aminotransferase activity, and liver cells showed slight proliferation of smooth endoplasmic reticulum, slight degranulation and splitting of rough endoplasmic reticulum and enlarged mitochondria, but no necrosis.
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PMID:Biochemical and morphological effects of long-term inhalation exposure of rats to ethylbenzene. 402 64

Biochemical and ultrastructural studies were carried out on the liver of male rats with a severe form of acute radiation disease. The animals were treated only once with a total dose of 6.7 Gy by means of a gamma-unit Rokus at the rate of 0.9 Gy per min. It was found that with the acute and severe form of radiation disease thus produced the activity of liver enzymes with cytoplasmic localization such as SDG, GPT, and GOT strongly rose in the blood plasma over the first 24 hours following treatment. The activity of ChE as an enzyme that was specific of the endoplasmic reticulum also rose. The normal ultrastructure of hepatocytes was unaffected over the first 24 hours after irradiation. Within the period of the clinical manifestation of the disease, however, there set in strongly expressed destructive changes in the mitochondria (from the eighth to the fifteenth day). It was concluded that the changes in the liver that were characteristic of the severe form of radiation disease set in early.
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PMID:[Biochemical and ultrastructural changes in the liver of rats with a severe form of acute radiation sickness]. 408 82

The present study, conducted over a time course of 36 hr after CCl4 administration, describes sequential morphometric and biochemical changes which occur in livers of rats exposed to a combination of low levels of chlordecone (10 ppm for 15 days) and a single ip injection of CCl4 (0.1 ml/kg). Those changes were compared to hepatic alterations which occur in rats that received the same dose of chlordecone or CCl4 alone. Biochemical studies showed only trivial increases in levels of glutamic-pyruvic transaminase (GPT), glutamic-oxalacetic transaminase (GOT), and moderate but temporary increases in isocitrate dehydrogenase (ICD) after CCl4 alone. The combination of chlordecone and CCl4 resulted in significantly greater elevations of all three serum enzymes at all time intervals examined. Morphometric data showed no difference between normal diet controls and animals exposed to chlordecone alone as far as numerical density of hepatocytes or volume densities of hepatocytes with glycogen, lipid, dilated rough endoplasmic reticulum (RER), pyknosis, or mitoses. Morphometric analysis of livers from animals that received CCl4 alone showed decreases in numerical density, temporary decrease in percentage of hepatocytes containing glycogen, an increase in hepatocytes containing lipid, temporary increase in hepatocytes with dilated RER, and temporary increases in pyknotic nuclei. Soon after the initial hepatic injury was histologically evident between 4 and 6 hr, the number of mitoses increased dramatically and this progressed until complete recovery from CCl4 damage. From all indices of damage, complete recovery was evident by 36 hr after CCl4 administration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chlordecone-induced potentiation of carbon tetrachloride hepatotoxicity: a morphometric and biochemical study. 619 13

Effect of a herbicide, paraquat (1,1'-dimethyl-4,4'-bipyridilium-dichloride), the fungicide copper sulphate, and zinc chloride was studied on the histological structure of liver, kidney and gill of three fish species with different feeding habits, viz.: a herbivorous, silver carp (Hypophthalmichthys molitrix); an omnivorous, common carp (Cyprinus carpio L.) and a carnivorous, sheatfish (Silurus glanis L.). The organs were studied electron microscopically after fixation according to Karnovsky. The toxic effect manifested itself characteristically on the respective species, regardless of the type of the chemical applied and the species specificity. Upon the effect of the treatments applied the cytoplasm of the respiratory cells of the gill became electron transparent and the cytoplasmic organelles disappeared almost totally. In the chloride cells showing focal necrosis, residuals of nuclear, mitochondrial and endoplasmic origin were seen. Pillar cells and the pericytes remained intact. In the nucleus of the liver cells, electron dense heterochromatin was not present. The degree of the damage in the liver cells was indicated by swollen mitochondria with electron transparent matrix and by dilatation and vacuolation of the endoplasmic reticulum system. Epithelial cells decreased in electron density, the endoplasmic reticulum was vesiculated, mitochondria were swollen. Leucocytes increased in number, and empty vacuoles and vacuoles filled with dense granules appeared in them during toxicosis. Copper sulphate or paraquat increased serum transaminase enzyme activities (glutamic acid-oxalacetic acid transaminase, glutamic acid-pyruvic acid transaminase) in all the three fish species. These damages can cause serious disturbances in energy uptake and secretion processes of fish.
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PMID:Morphological and biochemical studies on liver, kidney and gill of fishes affected by pesticides. 623 May 60

Bloodstream forms of Trypanosoma brucei have been screened for the presence of enzymes that could serve as markers for the plasma membrane, flagellar pocket, lysosomes, endoplasmic reticulum and Golgi apparatus in order to study the subcellular organization of the digestive system of the parasite. Acetylesterase, acid DNase, acid phosphatase, acid phosphodiesterase, acid proteinase, acid RNase, alanine aminotransferase, galactosyl transferase, alpha-glucosidase, inosine diphosphatase and alpha-mannosidase were partially characterized and their assays optimized for pH-dependent activity, linearity of reaction with respect to incubation time and enzyme concentration, and the effect of inhibitors and activators. The association of these enzymes with particulate material and the presence of structural latency were investigated. Acid proteinase and alpha-mannosidase are particle-bound and latent in cytoplasmic extracts; they can be activated and solubilized in part by Triton X-100. Similar results were obtained for acid phosphatase, acid phosphodiesterase and inosine diphosphatase. Neutral alpha-glucosidase, though partly sedimentable, does not show latency and is readily solubilized by the detergent. Galactosyl transferase is firmly membrane-bound even in the presence of 0.1% Triton X-100. Cell fractionation by differential centrifugation and density equilibration on sucrose gradients revealed that both alpha-mannosidase and acid proteinase are associated with organelles that band at a density of about 1.20 g/cm3. Inosine diphosphatase, galactosyl transferase, acid phosphatase and acid phosphodiesterase sediment predominantly as microsomal constituents equilibrating at densities between 1.13 and 1.15 g/cm3. In addition, inosine diphosphatase and galactosyl transferase exhibit considerable activity at higher densities (1.18-1.25 g/cm3). Neutral alpha-glucosidase is mainly recovered in the nuclear and microsomal fraction; its particulate part equilibrates as a single band at rho = 1.22 g/cm3. Acetylesterase and acid DNase are largely soluble, whereas acid RNase does not produce distinct sedimentation and banding profiles. In intact cells, neutral alpha-glucosidase and acid phosphatase appear to be highly accessible to their substrates. It is tentatively concluded that (a) acid proteinase and alpha-mannosidase are lysosomal enzymes, (b) acid phosphatase and acid phosphodiesterase are associated with the flagellar pocket and part of the former enzyme probably with the endoplasmic reticulum, (c) galactosyl transferase is a constituent of the Golgi apparatus, and (d) alpha-glucosidase may serve as a marker for the plasma membrane. Inosine diphosphatase may also be derived from the latter structure.
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PMID:Subcellular fractionation of Trypanosoma brucei bloodstream forms with special reference to hydrolases. 624 76


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