Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Piperine, a major pungent constituent of black and red peppers, was administered to rats intragastrically and intraperitoneally to study whether it alters the activities of hepatic mixed-function oxidases (MFO) and serum enzymes as specific markers of hepatotoxicity. An intragastric dose of 100 mg/kg of piperine to adult, male Sprague-Dawley rats caused an increase in hepatic microsomal cytochrome P-450 and cytochrome b5, NADPH-cytochrome c reductase, benzphetamine N-demethylase, aminopyrine N-demethylase and aniline hydroxylase 24 h following treatment. On the other hand, a 10 mg/kg dose given i.p. exhibited no effect on the activities of the aforementioned parameters of the hepatic drug-metabolizing enzyme system. However, when the intragastric and intraperitoneal doses were increased to 800 mg/kg and 100 mg/kg, respectively, the black pepper alkaloid produced a significant decrease in the levels of cytochrome P-450, benzphetamine N-demethylase, aminopyrine N-demethylase and aniline hydroxylase 24 h after treatment. None of the treatments significantly elevated the activities of serum sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and isocitrate dehydrogenase (ICD), suggesting that piperine is not a hepatotoxic agent.
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PMID:Comparison of the effects of piperine administered intragastrically and intraperitoneally on the liver and liver mixed-function oxidases in rats. 189 51

The destruction of liver microsomal cytochromes P450 by a previously administered low dose of CCl4 has been widely accepted as the mechanism of CCl4 autoprotection. However, circumstantial evidence suggests that this mechanism cannot completely explain the phenomenon of autoprotection. The protective effect of a low dose of CCl4 (0.3 ml/kg, po) on the lethal effect of a subsequently administered high dose (5 ml/kg, po) was established in male Sprague Dawley rats. The protective dose permitted 100% survival, whereas only 15% survival was observed without it. Hepatotoxicity, measured by serum enzyme elevations (aspartate transaminase, alanine transaminase, and sorbitol dehydrogenase) and histopathological changes 24 hr after the treatment with high dose, was similar in both the groups, even though the protective dose had significantly decreased liver microsomal cytochromes P450 (to 62% of normal) and associated enzymes, aminopyrine demethylase and aniline hydroxylase. Rats pretreated with CoCl2 to decrease hepatic microsomal cytochrome P450 to 44% of normal levels did not show a significant protection from the hepatotoxicity of high dose of CCl4. Previous studies have established that hepatocellular regeneration is stimulated within 6 hr after the administration of a low dose of CCl4. Based on this observation, a premise that autoprotection results from augmented recovery from injury rather than decreased injury appears likely. Hence, the role of hepatocellular regeneration was evaluated by following 3H-thymidine incorporation in hepatocellular nuclear DNA, labelling index by autoradiography, and by morphometric estimation of mitotic index. After administration of the protective dose of CCl4, stimulated nuclear DNA synthesis measured by 3H-thymidine incorporation into nuclear DNA was increased and this remained high even after subsequent administration of high dose of CCl4. Forty-eight hr after the administration of a lethal dose of CCl4 alone (5 ml/kg, po), labelling index was slightly increased, but mitotic index was not increased. In the surviving rats (15%), both labelling index and mitotic index were significantly elevated after an additional 24 hr. In rats receiving the protective dose, a significantly greater elevation of labelling index as well as mitotic index occurred 48 hr after the administration of the same lethal dose of CCl4. These results suggest that hepatocellular regeneration stimulated by the protective dose, as a biological response recruited to overcome the accompanying limited injury, may augment and sustain tissue repair processes to permit tissue restoration even after the massive liver injury elicited by the subsequent large dose of CC14.
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PMID:Role of hepatocellular regeneration in CCl4 autoprotection. 204 7

The effects of oral administration of different doses of the latex of Calotropis procera on the activities of drug-metabolizing enzymes in the liver, kidneys and duodenal mucosa of Nubian goats were investigated. Lesions and changes in total plasma protein concentration and in the activities of plasma sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate aminotransferase (AST) were studied. The daily oral administration of the latex at dose rates of 0.4 and 0.8 ml per kg for 7 days resulted in a significant inhibition of the activity of aniline 4-hydroxylase. No signfiicant effects on the activities of aminopyrine N-demethylase and UDP-glucuronyltransferase were observed. A single oral dose of 1.2 or 1.6 ml per kg killed goats within 7 h and resulted in increased activities of aminopyrine N-demethylase and aniline 4-hydroxylase. UDP-glucuronyltransferase was found to be insensitive to tissue injury induced by the latex of C. procera. There were no pathological changes in goats given 10 mg per kg of dieldrin alone or in those pretreated with dieldrin and given the latex at a dose rate of 1.2 ml per kg 14 days later. Dieldrin pretreatment resulted in the induction of the activities of drug-metabolizing enzymes in the liver, kidneys and duodenal mucosa and it may have protected goats from the lethal effects of the latex.
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PMID:The activities of drug-metabolizing enzymes in goats treated orally with the latex of Calotropis procera and the influence of dieldrin pretreatment. 206 26

Quail were fed monensin to determine liver damage, as measured by changes in activities of serum enzymes and liver microsomal enzymes. Monensin fed at a therapeutic level of 110 ppm for 2 weeks produced an increase in cytochrome P-450 and cytochrome b5 and induction of the activities of benzphetamine N-demethylase, aminopyrine N-demethylase, and aniline hydroxylase, with no changes in the activities of serum sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). On the other hand, quail fed 110 ppm, 220 ppm, and 330 ppm monensin in feed for 6 weeks showed a significant rise in SDH and AST activities at 330 ppm but not at 110 ppm and 220 ppm. The manifestations of liver toxicity observed at 330 ppm were accompanied by a significant decrease in all the aforementioned hepatic microsomal mixed-function oxidases. In contrast, quail fed monensin at 110 ppm and 220 ppm for 6 weeks produced no change in these parameters except for benzphetamine N-demethylase, aminopyrine N-demethylase, and aniline hydroxylase, which were significantly increased in birds fed 220 ppm of monensin.
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PMID:Toxicity of dietary monensin in quail. 224 82

The present investigation examines the possibility that Cd and ethanol have a significant toxicological interaction. This examination was warranted as exposure to either chemical is known to compromise human health. Inasmuch as both chemicals affect the morphology, biochemistry, and physiology of liver, it seemed reasonable to consider liver as a possible site of interaction. Specifically, the hypothesis that ethanol alters the hepatotoxic action of Cd was evaluated. Accordingly, male rats were injected iv with hepatotoxic (3.0 mg/kg) or lethal (4.5 mg/kg) dosages of Cd, 24 hr after single-dose ethanol administration (7 g/kg, po). Cd-induced hepatotoxicity was assessed by measuring the activities of alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase in serum collected 10 hr after Cd injection. Lethality was assessed by recording the number of survivors over a 7-day period. Prior exposure to ethanol substantially reduced the lethal and hepatotoxic properties of Cd. Two mechanisms were evaluated in an effort to explain ethanol-induced suppression of Cd hepatotoxicity. Ethanol pretreatment was postulated to: (1) enhance Cd excretion in bile thereby decreasing hepatic Cd content and/or (2) reduce the interaction between Cd and target sites in liver such as organelles and cytosolic high-molecular-weight (HMW) proteins. The first proposed mechanism was incorrect as the biliary excretion of Cd was nearly abolished and the concentration of Cd in whole liver increased (33%) as a result of ethanol exposure. The second proposed mechanism was a plausible explanation of ethanol-induced suppression of Cd hepatotoxicity because ethanol pretreatment decreased (approximately 60%) the content of Cd in nuclei, mitochondria, and endoplasmic reticulum, and nearly eliminated the association of Cd with cytosolic HMW proteins. Reduction in the concentration of Cd in potential target sites of intoxication was caused by a metallothionein-promoted sequestration of Cd in cytosol.
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PMID:Ethanol decreases cadmium hepatotoxicity in rats: possible role of hepatic metallothionein induction. 226 92

Intraperitoneal administration of acorn extract of dosage levels of 200, 400 and 600 mg/kg body weight did not produce significant change in the hepatic microsomal cytochrome P-450 levels and the activities of NADPH-cytochrome c reductase, benzphetamine N-demethylase and aniline hydroxylase in young, adult rats (weighing 200-250 g), with the exception of the activity of benzphetamine N-demethylase at the 600 mg/kg dose which was decreased significantly. On the other hand, a dose of only 100 mg/kg body weight ip to old rats (weighing 400-450 g) caused significant decreases in the microsomal cytochrome P-450, benzphetamine N-demethylase and NADPH-cytochrome c reductase activities. However, there was no significant change in the activity of aniline hydroxylase in these rats, indicating selective inhibition of the microsomal enzymes and higher susceptibility of old rats than young ones to acorn toxicants. When the serum samples from the treated young rats were analyzed for sorbitol dehydrogenase (SDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as markers of liver toxicity, these activities were significantly higher in the treated rats than the corresponding control values. Similar changes were noted for old rats receiving a dose of 100 mg/kg body weight of acorn extract. The results indicate that acorn extract affects old rats more than young rats as measured by its effect on liver and liver microsomal enzymes.
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PMID:Age-dependent toxicity of acorn extract in young and old male rats. 230 Nov 45

In a five-week feeding trial, 90 broiler chicks were used to study the response of serum and liver alanine aminotransferase (ALT) aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH) and alkaline phosphatase following the replacement of varying levels (0, 20, 40, 60, 80 and 100 per cent) of fishmeal protein by soyabean meal protein. The results showed that both serum ALT and AST activities increased significantly (P less than 0.01) with the increasing levels of substitution of soyabean meal for fishmeal. Regression analysis showed a significant (P less than 0.01) positive correlation between ALT and AST activities and the level of soyabean meal substitution with correlation coefficient, r, of 0.93 and 0.98, respectively. The liver ALT and AST tended to increase with the increasing proportion of soyabean meal although such increases were not significant (P greater than 0.01). Serum and liver SDH and alkaline phosphatase activities were not significantly influenced by diet.
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PMID:Dietary fishmeal versus soyabean meal: an assessment of serum and liver enzyme response in the chicken. 235 76

Serum activity of alanine aminotransferase (ALT) was consistently increased in dogs with canine X-linked muscular dystrophy (CXMD), a primary myopathy characterized by profound and on-going skeletal muscle necrosis. In order to determine whether the ALT was of liver origin, serum activity of creatine kinase (CK), aspartate aminotransferase (AST), ALT, and sorbitol dehydrogenase (SDH) obtained from dystrophic dogs was compared with enzyme activity present in clinically normal dogs. In dystrophic dogs at all ages tested, serum activity of CK, AST, and ALT was increased, and significant increases were present in dogs four weeks or older. In contrast, SDH activity in dystrophic dogs was not statistically different from values in clinically normal dogs. Ultrastructural examination of liver tissue revealed no evidence of hepatic degeneration in dystrophic dogs. It was concluded that increased serum activity of ALT in the dog may be associated with severe skeletal muscle degeneration, without concurrent hepatocellular necrosis.
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PMID:Increased serum alanine aminotransferase activity associated with muscle necrosis in the dog. 236 22

Elevated levels of serum enzymes are frequently associated not only with alcohol-related organ damage but also with excessive alcohol consumption and alcoholism without significant tissue injury. However, both in the early detection of alcoholism as well as also in the diagnosis of alcohol-related diseases the sensitivities and specificities of these enzyme markers vary considerably. They may be influenced by nonalcohol-related diseases, enzyme-inducing drugs, nutritional factors, metabolic disorders, age, smoking, etc. Consequently, we have neither a single laboratory test--enzyme marker--nor a test combination that is reliable enough for the exact diagnosis between alcohol- and nonalcohol-related organ damage. In most cases it is possible to determine the tissue from which the elevated enzyme is derived, but only occasionally enzyme changes reflect the quantity of the tissue injury. Gamma-glutamyltransferase (GGT) is the most widely used laboratory marker of alcoholism and heavy drinking, detecting 34-85% of problem drinkers and alcoholics. However, the unspecificity of increased serum GGT limits its use for general screening purposes. Its value in the follow-up of various treatment programs, however, is well established. An elevated level of serum aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in an alcoholic or a heavy consumer indicates alcohol-induced organ damage. The use of test combinations significantly improves the information received with single serum enzyme determinations. An ASAT/ALAT ratio greater than 1.5 can be considered as highly suggestive for the alcoholic etiology of the liver injury. Still better discrimination between alcoholic and nonalcoholic origin of the liver disease may be achieved by the determination of the ratio of GGT to alkaline phosphatase. If this ratio exceeds 1.4 the specificity of the finding in favor for alcoholic liver injury is 78%. The determination of the mitochondrial isoenzyme of ASAT also improves the diagnostic value of ASAT determination. The ratio of mitochondrial isoenzyme to total over 4 is highly suggestive for alcohol-related liver injury. In general, however, the determination of serum activities of other enzymes such as ornithine carbamyl transferase, lactate dehydrogenase, isocitrate dehydrogenase, sorbitol dehydrogenase, alcohol dehydrogenase, guanase, aldolase, alkaline phosphatase or glutathione S-transferase do not significantly improve the diagnostic information obtained with more conventional laboratory markers of liver injury.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Use of enzymes for the diagnosis of alcohol-related organ damage. 243 6

The suitability of DL-alpha-lipoic acid (LA) to serve as an antidote in cadmium (Cd) toxicity in rat hepatocytes was investigated. Isolated hepatocytes were exposed to 200 and 450 microM Cd in the presence of 0.2, 1.0 and 5.0 mM LA, respectively. After 30 min of incubation various criteria of cell viability were monitored. Lipoic acid markedly diminished Cd uptake. Concomitantly, Cd-induced membrane injury, as reflected by the leakage of aspartate aminotransferase and sorbitol dehydrogenase (SDH) was decreased. Moreover, LA protected against intracellular toxic responses to Cd, such as a decrease in cellular SDH activity, a decrease in cellular acid soluble thiols, especially in total glutathione, a decrease in cellular urea and an increase in thiobarbituric acid (TBA) reactants, as a measure of lipid peroxidation. Most protective effects were seen in hepatocytes challenged with the lower Cd concentration and coincubated with 5 mM LA. In contrast, at 450 microM Cd even the highest LA concentration applied either did only reverse Cd-effects incompletely (SDH-response, TBA-reactants) or did not protect at all (Cd uptake, enzyme leakage, loss of glutathione). The data indicate that DL-alpha-lipoic acid serves as a protective tool against Cd-induced membrane damage and cell dysfunction in hepatocytes. This stands as long as Cd exposure is low enough to permit interaction with LA prior to interaction with cell structures.
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PMID:Protective effects of DL-alpha-lipoic acid on cadmium-induced deterioration of rat hepatocytes. 250 68


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