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)

Two chimpanzees (Pan troglodytes) were inoculated and cross-challenged with a fibrinogen and factor VIII preparation, respectively. Successful non-A, non-B (NANB) infection was documented by biphasic elevations of aminotransferases (ALT), concomitant hepatitic reactions and typical electron microscopic alterations, the most consistent being dilatation of the endoplasmic reticulum, as well as tubular and sponge-like cytoplasmic inclusions in the absence of nuclear virus-like particles. An anti-nuclear (anti-DNA) antibody of the IgM class in one of the chimpanzees simulating an antiviral antibody is described.
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PMID:Experimental non-A, non-B hepatitis in chimpanzees: light, electron and immune microscopical observations. 630 79

There are reports in the literature that infection with hepatitis A virus in hepatitis B carriers can result in resolution of the carrier state. In an attempt to induce clearance of the carrier state of hepatitis B virus in two persistently infected chimpanzees, the chimpanzees were infused with documented non-A, non-B infectious material. Biochemical and histopathological evidence of hepatitis was accompanied by the unique abnormalities of endoplasmic reticulum associated with non-A, non-B hepatitis in the chimpanzees. Elevation of alanine aminotransferase was accompanied by fourfold reduction in one chimpanzee and sixfold reduction in the other in the plasma levels of HBV-associated DNA polymerase activity and simultaneously by twofold reduction in the concentration of hepatitis B surface antigen in both chimpanzees. A mediator may account for these changes in markers of hepatitis B virus infection, and this mechanism may also explain the occurrence of spontaneous regression in some persistently infected carriers. The significance of transient red cell anaemia in non-A, non-B hepatitis, which was observed in one of the chimpanzees, is yet to be established.
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PMID:Non-A, non-B hepatitis in persistent carriers of hepatitis B virus. 640 22

Ultrastructural changes in rat liver were studied 1, 2, 4, 6, 8, and 10 hr after administration of a single, high dose of Cd (3.9 mg Cd/kg, iv) or after repeated administration of a lower dose (0.5 mg Cd/kg, sc, 6 days/week for 6 months). These dosing regimens have been previously shown to produce hepatotoxicity and result in large accumulations of Cd in liver. In addition to light and electron microscopy, plasma enzyme activities indicative of liver injury, namely alanine (ALT) and aspartate (AST) aminotransferase, were determined at the aforementioned times. One hour after an acute dose of Cd, electron photomicrographs of liver showed dilation of the rough endoplasmic reticulum with concomitant loss of membrane-associated ribosomes, nucleolar condensation, and an increase in the number of perichromatin granules. At later times (4 and 6 hr), ultrastructural changes included mitochondrial swelling associated with matrical inclusions, further dilation and vesiculation of rough endoplasmic reticulum, and presence of a fibrillar material within cytoplasm. In contrast to changes observed after single administration of Cd, the predominant hepatic lesions in rats injected repeatedly with the metal over 6 months were interstitial fibrosis, nuclear enlargement, and an increase in number and predominance of nucleoli. Ultrastructural evidence of nuclear alterations included condensation of nucleoli and an increase in the number of perichromatin granules. These results indicate that Cd interferes with hepatic protein synthesis early after injection of a large dose, and that further degenerative changes occur later and possibly in response to protein inhibition. Although severe degenerative changes in liver were not evident in rats chronically exposed to the metal, Cd-induced changes in nuclei and nucleoli also indicate the likelihood of altered protein synthesis.
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PMID:Time course of cadmium-induced ultrastructural changes in rat liver. 648 85

The toxicity of 1-phenylcyclohexene (PC), a pyrolysis product of phencyclidine (PCP), and its interaction with PCP were evaluated. The ip LD50 of PC in Swiss male mice was 22 mmol/kg. Treatment of mice with PC at 2.2 mmol/kg/day, ip, for up to 7 days increased the liver/body weight ratio, which returned to normal within 7 days after PC withdrawal. Increases of 32% in serum glutamic-oxalacetic transaminase (SGOT) and 94% in serum glutamic-pyruvic transaminase (SGPT) were observed within 4 hr following the initial (Day 1) dose of PC. Smaller increases in the SGOT activity continued following Day 2 and 3 PC administrations. The SGPT activity remained elevated after these treatments. Activities of both enzymes, however, returned to normal within 24 hr following daily PC injections. No pathologic changes were observed in liver, brain, spleen, kidneys, and lungs with light microscopy. PC treatment for 4 days at 2.2 or 4.4 mmol/kg produced proliferation along with dilatation and fragmentation of the endoplasmic reticulum in liver. Scattering of ribosomes in the cytoplasm and dilatation of rough-surfaced cisternae were prominent at the higher dosage. Pretreatment of animals for 4 days with PC (1.1, 2.2, and 4.4 mmol/kg, ip) decreased pentobarbital- (60 mg/kg) induced sleeping time by 27, 64, and 80% and lowered PCP- (16.4 mumol/kg) stimulated locomotor activity by 18, 28, and 41%, respectively. Pretreatment of animals with PC for 1 hr inhibited (ED50: 2.3 mmol/kg) the PCP-induced locomotion. These results indicate that the PC treatment during a 7-day period produces some undesirable effects on liver function, which are reversible on its discontinuation. However, PC also weakens toxic effects of PCP.
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PMID:Toxicity of 1-phenylcyclohexene and its interaction with phencyclidine. 650 68

The role of dietary sucrose concentrations in the development of hepatic steatosis in rats was investigated. Twelve groups of weanling male Sprague-Dawley rats received semipurified diets with different sucrose concentrations ranging from 20 to 50% (w/w); one group received a cereal-based chow diet. Rats were sacrificed after 3 weeks and body weight, liver/body weight ratio, plasma alanine aminotransferase concentration, hepatic triglyceride concentration, and liver morphology (light and electron microscopy) were determined. Body weight and liver/body weight ratio were decreased in rats receiving 40-50 or 25-35% dietary sucrose compared to rats receiving 20% sucrose or chow. Plasma alanine aminotransferase concentrations were within normal limits. Hepatic triglyceride concentration was significantly increased in rats receiving 40-50 and 25-35% dietary sucrose compared to rats receiving 20% dietary sucrose or chow. Light microscopy showed hepatic steatosis in a periportal distribution at all concentrations of dietary sucrose. Both the frequency and the severity of the steatosis were increased with increasing dietary sucrose concentrations. Electron microscopy from selected livers with increased hepatic triglyceride concentrations revealed increased lipid spheres and increased smooth endoplasmic reticulum without prominent Golgi apparatus or GERL complex. It is concluded that high dietary sucrose concentrations are responsible for the development of hepatic steatosis. Semipurified diets with high dietary sucrose concentrations such as the AIN-76A diet (50% sucrose) should not be used in animal studies in which increased triglyceride deposition could influence experimental outcome.
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PMID:Hepatic steatosis in rats fed diets with varying concentrations of sucrose. 651 Jun 14

The influence of diazepam treatment following prolonged ethanol administration was toxicologically examined in rhesus monkeys and rats. In the monkey, ethanol was intragastrically administered through a chronically implanted catheter by programmed infusions at doses of 1.5 g/kg 4 times daily every 6 hours over a period of 5 or 10 weeks and followed by intragastric administration of diazepam 4 mg/kg twice a day for 5 weeks. In the rat, ethanol was administered by gavage at doses of 8 g/kg once a day or 4 g/kg twice a day for 5 weeks after which diazepam 300 mg/kg was intragastrically administered once daily for 5 weeks. In the monkey, ethanol produced such toxic changes as hypertriglyceridaemia, fatty metamorphosis of the hepatocytes associated with megamitochondria, proliferation of smooth endoplasmic reticulum and vacuolation in the hepatocytes, and gastritis. Diazepam did not aggravate but mostly alleviated these changes. In the rat, on the contrary, the serum GPT level slightly elevated due to the ethanol administration, and remained at the elevated level with the diazepam treatment in contrast with the complete recovery with non-treatment for 5 weeks after the ethanol administration. However, such changes as increase of fat droplets in the hepatocytes and the triglyceride concentration in the liver which had been developed by ethanol administration recovered during the diazepam treatment period. In spite of the recovery, the elevation of the serum GPT level being remained by diazepam may indicate possible influence of diazepam on the liver function when the drug is administered after prolonged administration of ethanol.
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PMID:Toxicological studies on the influence of diazepam following prolonged administration of ethanol in the rhesus monkey and rat. 666 57

Concurrent treatments of cobalt chloride (CoCl2) and phenobarbital (PB), alone or in combination with lithocholic acid (LCA), were administered to rats for 7 days to assess whether or not a hypoactive hypertrophic smooth endoplasmic reticulum (HHSER) could be induced, as well as investigating the potential role of HHSER in the pathogenesis of cholestasis. LCA given alone slightly reduced hepatic triglycerides, significantly elevated plasma triglycerides and decreased microsomal glucose-6-phosphatase (G6P-ase) activity. PB administered alone significantly increased hepatic phospholipids and microsomal protein, phospholipid and cytochrome P-450 contents, as well as microsomal aminopyrine-N-demethylase (APDM-ase) activity. Functional indicators of liver impairment were associated primarily with CoCl2 treatment, whether given alone or in combination with PB + LCA. These signs included significantly reduced hepatic triglycerides, and increased plasma triglycerides associated with enhanced release of hepatic VLDL-triglycerides, as well as significantly decreased microsomal G6P-ase activity and/or reduced APDM-ase activity and cytochrome P-450 content. Elevated plasma bilirubin levels, and aspartate and alanine aminotransferase activities were also evident with concurrent CoCl2 + PB + LCA treatments. Combined CoCl2 + PB treatments, with or without LCA, caused significant increases in microsomal protein and phospholipid, and decreased activity of the rough endoplasmic reticulum (RER) marker G6P-ase, but no changes in cytochrome P-450 levels and no marked alterations in the activity of the SER marker APDM-ase. The data indicated that simultaneous CoCl2 and PB treatments, whether given alone or in combination with LCA, caused a functional impairment of the RER, and did not induce HHSER membranes.
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PMID:Functional responses of the rat hepatic endoplasmic reticulum to treatment proposed as a model for cholestasis. 668 66

In the present study we first demonstrated that T-2 toxin markedly stimulated lipid peroxidation specifically in the liver of rats. The amount of lipid peroxides in the liver, estimated by the thiobarbituric acid (TBA) method, increased dose dependently, being proportional to the extent of its acute toxicity measured by various parameters in rats fed a commercial diet. Further, to elucidate the mechanism of lipid peroxidation and its role in hepatic injury caused by T-2 toxin, time-course studies on the correlation between lipid peroxide content and some biological and histopathological data were undertaken in rats given 4 mg of the toxin/kg perorally. The TBA reactive substances in the liver began to increase after 6 hr. However, much earlier than this there were some other alterations, which included decreases in the amount of cytochrome P-450 in the liver, of GPT (thereafter an increase) and phospholipids in the plasma, and of basophilic masses in the hepatocytes (arrayed as a rough endoplasmic reticulum in the electron micrograph). The vitamin E-deficient study showed that vitamin E markedly inhibited the stimulative effect of T-2 toxin on lipid peroxidation, but not diminish any other measured parameters of the injury. The toxin-induced stimulation of lipid peroxidation does not appear to be caused by activation of microsomal NADPH-cytochrome c reductase nor by a decrease in the level of cytosolic glutathione peroxidase. These results suggest that T-2 toxin might induce some alteration of the membrane structure and consequently might stimulate lipid peroxidation in situ.
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PMID:Elevation of thiobarbituric acid values in the rat liver intoxicated by T-2 toxin. 672 68

The effects of seasonal feeding on the structure and function of the hepatic microsomes of the reindeer were studied. In native microsomes the protein content did not vary depending on seasonal feeding, but there was a slight modification of the lipid moiety. The sensitivity of microsomes to membrane treatments changed from season to season. Seasonal feeding did not affect the hepatic cytochrome c reductase activity. However, the poor winter food depressed UDPglucuronosyltransferase activity to one third of that after summer feeding. The UDPglucuronosyltransferase activity was lower in both native and treated microsomes. No differences were found in serum activities of aspartate or alanine aminotransferase although there were changes in the structure and function of hepatocytes. The poor winter feeding of the reindeer decreases their capacity to glucuronate foreign compounds and this is mediated by structural modification on the hepatic endoplasmic reticulum.
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PMID:On the effects of nutrition on the metabolism of foreign compounds in the liver of reindeer (Rangifer tarandus tarandus L). 676 22

The hepatotoxic effects of cholelitholytic bile acids, ursodeoxycholic and chenodeoxycholic acids, were compared with each other and with those of lithocholic acid, a known hepatotoxic bile acid, in the rabbit. Male New Zealand white rabbits were fed regular laboratory chow containing ursodeoxycholic, chenodeoxycholic, or lithocholic acid at a concentration of 0.5 per cent (w/w) for 14 days. The control group was fed the chow without added bile acids. The mortality rate was highest (six of 12) in the lithocholate group, intermediate (two of eight) in the chenodeoxycholate group, and lowest (none of six) in the ursodeoxycholate group. Light microscopy of the liver revealed fibrosis, inflammation, and bile duct proliferation in the portal regions in the three experimental groups; however, the lesions in the lithocholate and chenodeoxycholate groups were more severe and often associated with periportal extension of fibrosis and focal necrosis of the parenchyma. In addition, electron microscopy revealed distortion of bile canaliculi, conspicuous bundles of intermediate-sized filaments, expansion of pericanalicular cytoplasmic matrix due to apparent accumulation of microfilaments, prominence of lysosomes, and fragmentation of cisternae of the rough endoplasmic reticulum. These ultrastructural changes were less marked and often absent in the ursodeoxycholate group. The serum L-alanine aminotransferase activity increased 5- to 6-fold in the lithocholate and chenodeoxycholate groups, whereas it remained less than 2-fold of the control level in the ursodeoxycholate group on day 14. The serum lithocholate concentration was markedly elevated to comparable levels in all three groups, whereas ursodeoxycholate was highly increased in the ursodeoxycholate group but undetectable in the other groups at the time of sacrifice. It is concluded that (1) although the oral administration of three bile acids induces hepatic injuries in the rabbit, ursodeoxycholate causes less severe injury than do the other two, (2) the advantage of ursodeoxycholate versus chenodeoxycholate is probably relative rather than absolute, (3) lithocholate formed through metabolic conversion from ursodeoxycholate may be responsible for the most part for hepatotoxicity, and (4) it is possible that the concurrent presence of ursodeoxycholate may mitigate lithocholate's hepatotoxicity.
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PMID:Hepatotoxicity of bile acids in rabbits: ursodeoxycholic acid is less toxic than chenodeoxycholic acid. 720 Jan 66


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