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)

Treatment of rats with 100 mg kg-1 t-butyl hydroperoxide led to an enhanced ethane exhalation as a marker of in vivo lipid peroxidation, as well as a moderate hepatoxicity as evidenced by a rise in plasma activities of liver-specific enzymes (glutamate-pyruvate transaminase and sorbitol dehydrogenase) and an increase in hepatic calcium content. Furthermore, a depletion of hepatic glutathione by 17% was observed. Apart from the loss of glutathione, all these effects were antagonized by pretreatment of rats with the potent iron chelator deferrioxamine and potentiated by pretreatment with low concentrations of FeSO4 having no pro-oxidant activity per se; this was also the case in rats under conditions of iron overload (experimental haemochromatosis). These data indicate a close relationship between t-butyl hydroperoxide-induced lipid peroxidation and its hepatotoxicity, and point out the importance of iron in catalysing reinitiation (propagation) reactions of lipid peroxidation in vivo.
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PMID:The role of iron in t-butyl hydroperoxide-induced lipid peroxidation and hepatotoxicity in rats. 225 81

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

The acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was examined in male C57BL/6J mice differing only at the Ah locus. Wild type mice (Ahb/b, "b/b") were treated once with 0, 50, 100, 200, 300, and 400 micrograms TCDD/kg po while congenic mice (Ahd/d, "d/d") received a single dose of 0, 400, 800, 1600, 2400, and 3200 micrograms TCDD/kg. Mice were checked daily, weighed twice a week, and those that survived, killed 35 days post-treatment. The LD50 values were 159 and 3351 micrograms/kg for b/b and d/d mice, respectively. Mean time to death was 22 days and was independent of dose and genotype. Decrease in body weight gain was noted in both strains 5 days after treatment and occurred at doses greater than or equal to 100 micrograms/kg in b/b mice and 1600 micrograms/kg in d/d mice. Dose-related increases in liver weight (both absolute and relative to body weight) and decreases in thymus, spleen, testes, and epididymal fat pad weights were observed at 8-24-fold higher doses in d/d than in b/b mice. A dose-related increase in segmented neutrophils was observed in both strains. Serum chemistry values indicated that 8-24X greater doses of TCDD were needed to elevate sorbitol dehydrogenase, alanine aminotransferase, and 5'-nucleotidase and to decrease total and esterified cholesterol in d/d than in b/b mice. Few effects were seen on total bile acids, serum triglycerides, glucose, or nonesterified cholesterol. In the liver, hepatocellular cytomegaly, fatty change, and bile duct hyperplasia occurred in both strains in a dose-related manner, as did thymic and splenic atrophy. Necrosis of germinal epithelium in the testes and edema in the stomach submucosa occurred at acutely toxic doses. These lesions also occurred at doses 8-24X greater in d/d than in b/b mice. Thus, the spectrum of toxicity is independent of the allele at the Ah locus, but the relative dose needed to bring about various acute responses is approximately 8-24X greater in congenic mice homozygous for the "d" allele than for the wild type animals carrying two copies of the "b" gene.
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PMID:Differential toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C57BL/6J mice congenic at the Ah Locus. 237 98

Mercuric chloride was administered once i.p. to female Fischer-344 rats at doses of 0, 0.2, 0.6 and 1.8 mg/kg. Although there were no alterations in the urinary excretion of lactate dehydrogenase, significant elevations in the activities of urinary (U) alkaline phosphatase, glutamic-pyruvic transaminase (GPT) and glutamic-oxalacetic transaminase (GOT) indicated that mercuric chloride was nephrotoxic. There was no evidence of hepatotoxicity as hepatic glucose-6-phosphatase and serum sorbitol dehydrogenase were essentially unaffected by mercuric chloride administration. The activities of ethylmorphine demethylase, hexobarbital oxidase and aldrin epoxidase determined in vitro were not inhibited by mercuric chloride although aniline hydroxylase activity was decreased. Of the four phase-II reactions measured, only the glucuronidation of chloramphenicol was diminished by treatment with mercuric chloride. Results from the in vivo studies on the metabolism of lindane, which indicated no change in the excretion of free or conjugated metabolites, were in close agreement with the in vitro data suggesting that the nephrotoxic effects of mercuric chloride do not alter the urinary excretion of the model substrate lindane.
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PMID:A comparison of in vitro and in vivo methods for evaluating alterations in hepatic drug metabolism following mercuric chloride administration. 242 44

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

Acetaminophen (AA) was administered i.p. to Swiss mice as a single dose 100, 200, 300, 400 and 600 mg/kg. At different time periods after administration, the mice were sacrificed. Serum glutamate-pyruvate transaminase (SGPT) and sorbitol dehydrogenase (SDH) as well as glutathione (GSH) levels in the liver were determined. It was found that the effective dose ranged within 200-600 mg/kg. Changes in GSH level occurred shortly after acetaminophen administration, whereas changes in the activity of indicatory enzymes were slightly delayed compared to this process. Conditions allowing for parallel observations of all three indices under investigation occurred 4 hrs after acetaminophen administration. With regard to glutathione, directly measured decrease, as compared to control levels, may be used as the yardstick of the changes. Changes in the activity of indicatory enzymes may be better expressed in the dose-response arrangement. For all the indices determined 4 hrs after acetaminophen administration, ED50 is in the range 200-300 mg/kg.
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PMID:Dynamics of glutathione levels in liver and indicatory enzymes in serum in acetaminophen intoxication in mice. 248 10

This investigation was undertaken to assess the potential of ingested 1,2-dibromo-3-chloropropane (DBCP) to cause testicular and hepatorenal injury, in light of the paucity of data applicable to risk assessment of DBCP in drinking water. Adult male Sprague-Dawley rats were supplied ad libitum with water containing 0, 5, 50, 100, and 200 ppm DBCP for 64 days. A dose-related decrease in water consumption occurred during the study. The 200-ppm animals drank less than half as much water as controls, consumed less food, and subsequently exhibited significantly lower body weight gain. DBCP ingestion thus was not directly proportional to the level of chemical in the water, although daily and cumulative intake of DCP were concentration dependent. Average daily intake of DBCP for the 64-day exposure period was as follows: 5 ppm = 0.4 mg/kg/day; 50 ppm = 3.3 mg/kg/day; 100 ppm = 5.4 mg/kg/day; 200 ppm = 9.7 mg/kg/day. Blood samples were taken after 2, 4, and 6 weeks of exposure and at the terminal sacrifice and assayed for serum glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, sorbitol dehydrogenase, and ornithine-carbamyl transferase activities and BUN levels. No evidence of liver damage at any exposure level was indicated by either the clinical chemistry indices or histopathology. Histologic examination revealed an apparent increase in the number of nuclei per renal proximal tubule cross-section in the 200-ppm group, possibly indicative of an increased turnover of proximal tubular cells. A slight, but statistically significant, decrease in absolute testicular weight was manifest in the 200-ppm animals, although the decrease was not significant when testicular weight was calculated as g/100 g body wt. Epididymal sperm counts and serum luteinizing hormone, follicle stimulating hormone, and intratesticular testosterone levels were not altered by any dose of DBCP. A qualitative histopathological examination of the testicular seminiferous epithelium failed to reveal any abnormalities in the spermatogenic process.
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PMID:Assessment in rats of the gonadotoxic and hepatorenal toxic potential of dibromochloropropane (DBCP) in drinking water. 262 Jul 97


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