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)

The effect of Laennec (human placenta hydrolysate) on CCl4-induced acute or chronic liver injury in rats was examined. In the acute liver injury induced by CCl4, 0.5 ml/kg for 4 days, intravenous injection of Laennec increased total protein and decreased nonesterified fatty acid in the liver. Subcutaneous injection of Laennec inhibited the decrease of liver phospholipid by CCl4 administration. Both intravenous and subcutaneous injections of Laennec inhibited the increases of serum transaminase (GOT, GPT) levels caused by CCl4. Furthermore, intravenous Laennec inhibited the increase of serum alkaline phosphatase level. Pathological examinations of the liver indicated that both intravenous and subcutaneous injections of Laennec inhibited the loss of cytoplasma and nuclei, vacuolation, swelling and necrosis in the centrizonal hepatocytes caused by CCl4. Intravenous and subcutaneous injection of Laennec also inhibited the increases of GOT and GPT levels in rats with chronic liver injury caused by CCl4, 0.5 ml/kg for 7 weeks. Both intravenous and subcutaneous injections of Laennec minimized the pathological changes of the liver by CCl4 such as vacuolation, necrosis and swelling of nuclei, but did not inhibit the formation of pseudolobules. Thus, no therapeutic difference was noted between intravenous and subcutaneous injections of Laennec.
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PMID:[A comparative study of Laennec by intravenous or subcutaneous injection on CCl4-induced acute or chronic liver injury in rats]. 280 70

The role of thromboxane A2 (TxA2) in CCl4-induced liver disease was investigated in mice. Significant elevation of TxB2 in the liver was observed 6 hours after the injection of CCl4. Administration of OKY-046, a selective TxA2 synthetase inhibitor (10 and 50 mg/kg) and ONO-3708, a TxA2 receptor antagonist, (0.5, 1 and 2 mg/Kg) suppressed the elevation of serum GOT and GPT levels and histopathological changes of the liver. In addition, OKY-046 inhibited the elevation of TxB2 in the liver. When U-46619, a stable TxA2 mimetic was injected i.v. into the mice, clear elevation of serum GOT and GPT levels and histopathological score of the liver were observed. These results suggest that TxA2 play a role for the onset of CCl4-induced liver injury in mice.
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PMID:The role of thromboxane A2 [TxA2] in liver injury in mice. 281 11

The relation among the blood clearance of 99mTc-phytate (99mTc-P), the hepatic uptake of 99mTc-P and the severity of hepatic injury was investigated by using the rats with carbon tetrachloride (CCl4), D-galactosamine (Gal N), alpha-naphthylisothiocyanate (ANIT) or DL-ethionine (EthN) induced hepatic injury. After the administration of CCl4, GalN or ANIT, serum GPT activity increased significantly with the increase of dose level, and the degree of this increase was in the order: GalN greater than CCl4 greater than ANIT. However, the mild increase in serum GPT activity was observed after EthN administration. The blood clearance rate of 99mTc-P and the hepatic uptake ratio of 99mTc-P decreased with the increase of dose level after CCl4, GalN or ANIT administration, but significant changes were not found after EthN administration. The degree of decrease in the blood clearance rate of 99mTc-P was in the order: GalN not equal to CCl4 greater than ANIT, and the degree of decrease in the hepatic uptake ratio of 99mTc-P was in the order: GalN not equal to CCl4 greater than ANIT. These results suggest that the disorder in the hepatocytes may be one of causes for inducing the decrease in the hepatic uptake of 99mTc-P, and the consequence of this decrease may induce the decrease in the blood clearance of 99mTc-P.
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PMID:Relation between blood clearance and hepatic uptake of 99mTc-phytate in rats with hepatic injury. 281 59

A detailed analysis is presented of the time changes in the development of liver damage 6, 12, 24, 48 and 72 hours after i.p. administration of carbon tetrachloride [CCl4] in a dose of 0.75 ml, i.e. 1 200 mg/kg body weight to rats of both sexes. The severity of liver damage was assessed from the histological and biochemical changes of AST, ALT, alkaline phosphatase and GMT serum activity. From our experiments it follows that in male rats the level of transaminases increases earlier than in female rats, as early as 6 h after the administration of CCl4, reaching a maximum 12 h later. These changes prevail for a longer time period, the level of transaminases remaining increased even 72 h after CCl4 administration. In female rats the biochemical changes occur later reaching the maximum elevation of AST and ALT 24 h after CCl4 administration. The values slowly return to normal after 48 h, and after 72 h the levels of transaminases are identical with the control group. The above given biochemical results are in good agreement with the histological findings demonstrating a higher regenerative activity in female rats. This finding was also proved by specific liver DNA activity assay.
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PMID:The time course of biochemical and histological changes following carbon tetrachloride-induced liver damage in rats of both sexes. 286 69

We have compared the effects of BW755C, a dual inhibitor of the arachidonic acid cyclo-oxygenase and lipoxygenase, with the effects of colchicine and indomethacin on the reversion of the biochemical and histochemical signs of rat liver cirrhosis. This was induced by i.p. administration of CCl4 for 11 weeks. At this point the rats were divided into four groups (10 animals each). CCl4 administration was continued for one month along with either colchicine, BW755C or indomethacin. No additional treatment was given to the control group. BW755C consistently improved all the parameters studied. Although colchicine also improved all but two markers (serum ALT activity and serum proteins) it ranked lower than BW755C in most of them. Indomethacin only modified favourably serum alkaline phosphatase activity, serum proteins, cholesterol and bilirubins and liver collagen content. The effects of BW755C could be mainly attributed to the inhibition of the lipoxygenase pathway. A common feature of colchicine, adrenal steroids and BW755C was the ability to inhibit the formation of leukotriene and other lipoxygenase products. The possibility that this property might contribute to their anti-cirrhotic actions is discussed.
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PMID:Reduction of apparent indicators of liver cirrhosis in rats by the arachidonate lipoxygenase inhibitor BW755C. 288 11

The effects of colchicine (10 g/day p.o. for 7 days) and rioprostil (2-decarboxy, 2-hydroxymethyl-15-deoxy-16-RS-hydroxy-16-methyl-prostaglandin-E1) (20 g/kg s.c., a single dose) on the enzymatic and histological markers of acute liver damage were studied in rats intoxicated with a single oral dose of CCl4. The rats were sacrificed 24 h after CCl4. The lipid composition of the liver plasma membranes was also determined. The increase in Alk. Phosp., GGTP and GPT activities and bilirubin concentration in serum as well as the histological images produced by CCl4 were equally prevented by the treatments with colchicine or rioprostil. CCl4 changed the lipid composition of the liver plasma membrane by increasing PI and PC and decreasing SM, PS and PEA. There was a decrease in the cholesterol/phospholipid ratio at the expense of a reduction of cholesterol/protein ratio and elevation in phospholipid/protein ratio. Colchicine and rioprostil also prevented these lipid alterations. The results suggest that the plasma membrane is an important site of action of CCl4 and of the 2 drugs studied. We postulate that the plasma membrane rather than other organelles is the target for the cytoprotective actions of prostaglandins.
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PMID:Effect of rioprostil and colchicine on CCl4-acute liver damage in rats. Relationship with plasma membrane lipids. 289 Jan 82

Copper is believed to be hepatotoxic in Indian Childhood Cirrhosis and Wilson's disease. However, copper-loading causes only minimal hepatic damage in animal models. The hypothesis was therefore proposed that a second hepatic insult may precipitate or perpetuate liver injury in a copper-laden liver. In non-copper-dosed rats CCl4 (10 mmol/kg, i.p.) produced elevated serum AST (809 +/- 298 IU/l, normal 20 +/- 5) and ALT (295 +/- 157 IU/l, normal 6 +/- 1) and extensive liver cell necrosis, portal tract inflammation, fat deposition, and perilobular hepatocyte ballooning. In rats whose liver copper was elevated from 75 +/- 13 to 461 +/- 13 micrograms/g by oral copper supplementation, CCl4 produced much smaller increases in AST (492 +/- 80 IU/l) and ALT (172 +/- 57 IU/l) and mild focal liver cell necrosis. Fat deposition and perilobular vacuolation were not reduced. Prior copper-loading of rats unequivocally protected against the CCl4-induced liver injury. Triglyceride accumulation, however, was apparently unaffected. The possible interactions of copper with prostaglandin-mediated inflammation and with free-radical-induced liver damage are discussed.
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PMID:The effect of carbon tetrachloride on the copper-laden rat liver. 292 91

The effects of carbon tetrachloride (CCl4), following 7 consecutive days of exposure ip at 500, 1000, and 1500 mg/kg, were determined on murine humoral and cell-mediated immune responses, body and organ weights, spleen cell blastogenesis following mitogenic stimulation, and clinical serum parameters for liver injury. In vivo sensitization of CCl4-treated B6C3F1 mice resulted in a dose-dependent suppression of the T-dependent antibody response to sheep red blood cells (sRBC) at all doses--36, 48, and 53%, respectively. The T-independent in vivo antibody response to DNP-Ficoll was suppressed only at 1500 mg/kg, and only by approximately 16%. This dosing regimen also resulted in a significant decrease in thymus weights; however, there were no significant effects on liver, kidney, lung, or body weights. The serum chemistry profile indicated a dose-dependent increase in serum glutamic-pyruvic transaminase (SGPT) levels (34-, 47-, and 55-fold) and a non-dose-dependent increase in serum bilirubin and total protein. Serum glucose and albumin levels were unaffected. Splenocytes from mice treated with 1500 mg/kg and sensitized in vitro with antigen demonstrated a comparably suppressed antibody response to the antigens sRBC and DNP-Ficoll as observed in vivo--66 and 28% respectively. This dose of CCl4 had no effect on the in vitro antibody response to the polyclonal antigen lipopolysaccharide. The mixed lymphocyte response was dose dependently suppressed following CCl4 exposure; however, the delayed-type hypersensitivity response was unaffected. Lymphocyte blastogenesis following mitogenic stimulation with lipopolysaccharide or concanavalin A was also inhibited by CCl4 exposure. These studies demonstrate that exposure to CCl4 results in a marked suppression in both humoral and cell-mediated immune responses at concentrations which also affect the liver as evidenced by the marked increase in SGPT levels.
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PMID:Suppression of humoral and cell-mediated immune responses by carbon tetrachloride. 292 10

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

The ability of 14 serum biochemical assays to predict the presence of hepatic necrosis induced by carbon tetrachloride (CCl4) (centrilobular necrosis), allyl alcohol (periportal necrosis), and 1-napththylisothiocyanate (ANIT) (biliary duct necrosis) was evaluated in rats. Results of these assays were analyzed using multivariate discriminant analysis to determine: which assays have the highest predictive value for discriminating between control and treated rats, and which assays would discriminate between rats in the three treatment groups. Individual assays with the highest predictive value for CCl4-induced lesions versus controls were glutamate dehydrogenase (GDH), sorbitol dehydrogenase (SDH), and alanine aminotransferase (ALT). Assays with the highest predictive value for ANIT-induced lesions were GDH, 5'-nucleotidase (5'NT), and ALT. Assays the highest predictive value for ANIT-induced lesions were GDH, 5'-nucleotidase (5'NT), and ALT. Assays with the highest predictive value for allyl alcohol-induced lesions were an ALT/isocitrate dehydrogenase (ICD) ratio, GDH, and ALT. Canonical correlation coefficients for each assay ranged from 0.98 to 0.91 with 95-100% correct group membership predictions (treated versus control) provided by each assay. Individual assays were not highly predictive for determining group membership among all three treatment groups. A two assay combination of 5'NT and an ALT/ICD ratio provided 100% correct group membership predictions and had high canonical correlations (f1 = 0.95, f2 = 0.83).
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PMID:Evaluating toxin-induced hepatic injury in rats by laboratory results and discriminant analysis. 301 5


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