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

---

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

Administration of large doses of acetaminophen or cocaine to male CD-1 mice produces significant hepatic injury with marked elevation in serum glutamate-pyruvate transaminase activity and severe hepatocellular necrosis. The proposed mechanism for this phenomenon is activation of both parent compounds to hepatotoxic metabolites. Ascorbic acid, 1 g/kg, given to mice 1 hour before and 1 hour after either acetaminophen or cocaine treatment prevented development of the severe hepatocellular damage observed with administration of either drug alone. Plasma disappearance of acetaminophen was less rapid in ascorbic acid-treated animals, suggesting that in vivo metabolism of acetaminophen was altered by ascorbic acid treatment. However, ascorbic acid treatment alone produced a modest decrease in hepatic glutathione content and did not prevent marked hepatic glutathione depletion when administered concomitantly with acetaminophen. Furthermore, a 2-mM ascorbic acid concentration did not alter in vitro hepatic microsomal metabolism of cocaine as measured by formaldehyde formation. While the mechanism(s) for its protective effect remains to be elucidated, these results raise the possibility that ascorbic acid may be useful in preventing hepatic injury caused by some hepatotoxic drugs.
...
PMID:Ascorbic acid protects against acetaminophen- and cocaine-induced hepatic damage in mice. 651 Feb 39

Hyperbaric oxygen (HPO) was administered to rats (100% O2 at 2.8 atm for 90 min) immediately or 1 hr after severe carbon tetrachloride (CCl4) intoxication in order to study the mechanisms of protection against hepatocellular injury by hyperoxia. Slight to moderate hepatocellular injury was observed, particularly by morphologic criteria, 4 hr after CCl4 intoxication. Little cell death was observed; 24 hr after CCl4, 20% of the untreated animals died. In the survivors, the following typical changes occurred in the liver: extensive hepatocellular swelling, vacuolization and necrosis; severe ultrastructural alterations; binding of CCl4 to microsomal lipids; elevation of lipid peroxidation products (conjugated dienes); little decrease in cytochrome b5 and severe decrease in cytochrome P-450 levels. Serum transaminase (alanine aminotransferase and aspartate aminotransferase) levels were elevated. Immediate treatment with HPO prevented the mortality and markedly decreased the hepatocellular necrosis 24 hr after intoxication. Immediate HPO treatment did not lower the levels of free CCl4 in the liver. However, the rise in lipid peroxidation products caused by CCl4 intoxication at 4 hr was reduced. Delayed treatment with HPO (1 hr after CCl4) prevented the mortality but was less effective in preventing necrosis. Some hepatocellular protection was still demonstrable. In particular, the rise in lipid peroxidation products was reduced. Hyperoxia protects hepatocytes against CCl4 toxicity. The rapid decline in protective effect within 60 min of intoxication suggests that hyperoxia inhibits CCl4 activation and/or damage from molecular intermediates. Hyperoxia has little effect on the progression of sublethal injury to cell death in the livers of CCl4-intoxicated rats.
...
PMID:Protection of hepatocytes with hyperoxia against carbon tetrachloride-induced injury. 653 53

To study the relationship between lipid peroxidation and cellular damage we studied three compounds known to evoke lipid peroxidation (cumene hydroperoxide, CHP), hepatocellular injury (thioacetamide, TAA) or both (carbon tetrachloride, CCl4). Phenobarbital-induced male rats were treated with one of the three agents and lipid peroxidation was monitored via the measurement of exhaled ethane. Treatment with both, CCl4 and CHP resulted in an increased ethane expiration, whereas TAA did not. When liver-specific serum enzyme activities (GPT, SDH) were investigated 24 h later, however, hepatotoxicity was evident only in rats treated with either CCl4 or TAA. The ATP-dependent Ca2+-sequestration activity of microsomal membranes, suggested to be a final common pathway leading to cellular death, was studied in microsomes isolated from rats treated with either agent. 2 h after treatment with CCl4 or TAA a clear inhibition was seen which persisted after 24 h in the case of CCl4 only. CHP did not affect the Ca2- -pump activity. Thus, a clear correlation between cellular damage and lipid peroxidation cannot be expected in every case. An impairment of the microsomal calcium-pump, however, seems to be a crucial event which leads to hepatocellular injury.
...
PMID:Interrelationship between in vivo lipid peroxidation, microsomal Ca2+-sequestration activity and hepatotoxicity in rats treated with carbon tetrachloride, cumene hydroperoxide or thioacetamide. 662 17

Acute or chronic treatment of rats with isopropanol caused a significant increase in hepatic cytochrome P-450 content and a two- to threefold increase in aniline hydroxylase and 7-ethoxycoumarin O-deethylase activities, but no significant change in ethylmorphine N-demethylase or benzo(a)pyrene hydroxylase activity. In rats treated with isopropanol and challenged with CCl4, liver toxicity of CCl4 was characteristically potentiated, as assessed by elevation of serum glutamic-pyruvic transaminase (SGPT) levels. Isopropanol pretreatment also potentiated CCl4-induced damage to the hepatic monooxygenase system. In addition to a decrease in cytochrome P-450, rats treated with isopropanol and challenged with CCl4 showed a nonspecific decrease not only in aniline hydroxylase and 7-ethoxycoumarin O-deethylase activities, but also in ethylmorphine N-demethylase, benzo(a)pyrene hydroxylase, and NADPH-cytochrome c reductase activities. These results were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of solubilized microsomes. The electrophoretic results showed that isopropanol pretreatment markedly potentiated the CCl4-caused destruction of cytochrome P-450 hemeproteins. The data strongly suggest that isopropanol increases one or more forms of cytochrome P-450 which selectively enhance the metabolism of CCl4 to an active metabolite. This active metabolite then causes a nonselective damage to the microsomal mixed-function oxidase system.
...
PMID:Isopropanol enhancement of cytochrome P-450-dependent monooxygenase activities and its effects on carbon tetrachloride intoxication. 663 85

The toxic effects of paraquat administered to rats in drinking water for a period of 30 days were studied. Paraquat had no effect on the body weight gain or on organ weights of rats. However, microsomal NADPH-cytochrome c reductase activity and cytochrome P-450 content were increased in rats given paraquat in drinking water. The obtained differences were statistically significant. Serum alkaline phosphatase activity was not significantly changed with respect to control animals but a statistically changed, with respect to control animals, statistically significant decrease was established in serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase activity of test animals compared to values obtained for control groups. Hematological data showed that paraquat caused a decrease in hemoglobin concentration and total red blood cell number, while the total white blood cell number was significantly increased compared to values obtained for control animals.
...
PMID:Subacute toxicity of paraquat in rats--biochemical effects. 664 84

The effects of promethazine (PM) on different aspects of the hepatotoxic action of CCl4 in the rat were investigated with the objective of finding rapid and reliable indicators of hepatoprotective effects. The study was based on definitive histological assessment of liver damage caused by CCl4 in the presence and absence of PM: PM (78 mumol kg-1, i.p.) protected against CCl4-induced hepatic necrosis 24 h after a low dose of CCl4 (1.3 mmol kg-1) but not against a higher dose (13.0 mmol kg-1). The large increases in plasma activities of GOT, GPT and LDH produced by dosing with CCl4 were partially inhibited by the administration of PM. PM and CCl4 caused a synergistic and long-lasting decrease in body temperature (2-3 degrees C for 8-10 h). Modifying the toxicity with PM, together with a low dose of CCl4, helped to minimize secondary effects of CCl4, to clarify the sequence of toxic events, and to assess the sensitivity of some standard tests of hepatotoxicity. Simultaneous measurement of over 20 commonly used biochemical screening tests in individual animals 3 or 6 h after treatment permitted direct correlation of a wide variety of concentrations, activities and effects. For example, liver CHCl3 concentrations (as a measure of CCl4 metabolism) correlate strongly with increases in diene conjugation of microsomal lipids (as a measure of CCl4-induced lipid peroxidation); malonaldehyde production appears to be less sensitive as a measure of lipid peroxidation in vivo than diene conjugation. The changes induced in each parameter and the correlations between them are discussed with reference to the overall nature of the hepatotoxic reaction and its modification by PM.
...
PMID:Correlations between common tests for assessment of liver damage: indices of the hepatoprotective activity of promethazine in carbon tetrachloride hepatotoxicity. 667 18

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.
...
PMID:Functional responses of the rat hepatic endoplasmic reticulum to treatment proposed as a model for cholestasis. 668 66

The effects of allyl alcohol, galactosamine, bromobenzene, and corn oil administration were evaluated in male Fischer 344 rats at 4 to 5, 14 to 15, and 24 to 25 months of age to determine if susceptibility to hepatotoxic injury is modified as a consequence of aging. Parameters measured were (1) severity of hepatocellular necrosis as judged by light microscopy of liver sections, (2) activity of alanine aminotransferase and aspartate aminotransferase in serum, and (3) hepatic microsomal cytochrome P-450 content and NADPH-cytochrome P-450 reductase activity. Allyl alcohol toxicity was more severe in middle-aged and old rats than in young-adult rats. In contrast, galactosamine and bromobenzene toxicities were slightly decreased or unchanged in old rats. The results demonstrate that aging has effects on some types of chemically induced hepatotoxicity.
...
PMID:Influence of aging on the susceptibility of rats to hepatotoxic injury. 671 May 24

Previous studies indicate that pretreatment with acetone or isopropanol, fasting, and streptozotocin-induced diabetes enhance hepatic microsomal nitroso-dimethylamine (NDMA) demethylase in rats. This study demonstrates that these same treatments also potentiate the hepatotoxicity of NDMA as indicated by plasma glutamic pyruvate transaminase (GPT) levels and histologic data. Pretreatment with acetone or isopropanol (2.5 ml/kg) and 2 days of fasting caused a 2-fold potentiation of NDMA-induced plasma GPT elevation, whereas streptozotocin-induced diabetes caused a 4.6-fold potentiation. The centrilobular necrosis produced by NDMA was more severe after pretreatment with the inducers. NDMA treatment also decreased hepatic microsomal demethylase activity. These results lend support to the concept that a NDMA demethylase is responsible for the activation of NDMA in vivo to a toxic intermediate, and induction of this enzyme activity potentiates NDMA hepatotoxicity.
...
PMID:Potentiation of the hepatotoxicity of N-nitrosodimethylamine by fasting, diabetes, acetone, and isopropanol. 671 61

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.
...
PMID:Elevation of thiobarbituric acid values in the rat liver intoxicated by T-2 toxin. 672 68


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

---