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)

2,3,7,8-Tetrabromodibenzo-p-dioxin (2,3,7,8-TBDD) was administered daily to male and female rats for 91 days by gavage. Ten male and 10 female rats per group received 0.01, 0.1, 1, 3, or 10 micrograms 2,3,7,8-TBDD/kg body weight per dose per day, solubilised in arachis oil. At 1 microgram/kg per day and above, body weight gain was dose-dependently reduced by treatment. Animals in the 3 and 10 micrograms/kg dose groups showed symptoms of wasting syndrome. Fifty percent of the animals in the 3 micrograms/kg dose-group died and all animals of the highest dose (10 micrograms/kg) died or had to be killed in extremis. Hematological investigations indicated changes--mainly in the 1 and 3 micrograms/kg dose-groups--in hemoglobin content, packed cell volume and number of thrombocytes. The prothrombin-time was markedly prolonged after 3 micrograms/kg in week 13. Clinical chemistry performed at the end of treatment revealed an increase in plasma alkaline phosphatase (APh), aspartate aminotransferase, ASAT and alanine aminotransferase, ALAT (females only) in the highest surviving dose-group (3 micrograms/kg). Marginal changes of APh and ASAT were seen in rats in the 1 microgram/kg dose-group. In the same animals, total bilirubin was elevated. Triglycerides were reduced mainly at 1 and 3 micrograms/kg. Serum thyroxin was reduced, beginning with a marginal change at 0.1 micrograms/kg, triiodothyronine was elevated, starting with a dose of 1 microgram/kg. Thymus weights were reduced in rats of the 1, 3 and 10 micrograms/kg dose-groups. Histopathological analysis showed atrophy of the lymphatic tissue in thymus and spleen. Investigations of the liver indicated peliosis hepatis after treatment with 3 or 10 micrograms/kg. Activities of microsomal enzymes (ethoxyresorufin O-deethylase, ethoxycoumarin O-deethylase, aryl hydrocarbon hydroxylase, UDP-glucuronyltransferase) investigated in liver, lung and kidney were dose-dependently elevated after 13 weeks of treatment. At a dose of 3.0 micrograms/kg, activities were below those of the dose 1.0 microgram/kg, probably due to liver toxicity. The induction ratio of kidney was generally higher than in liver and lung. No signs of treatment-related toxicity were observed in the 0.01 and 0.1 micrograms/kg groups after the subchronic administration of 2,3,7,8-TBDD by gavage.
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PMID:Subchronic toxicity of 2,3,7,8-tetrabromodibenzo-p-dioxin in rats. 824 44

Benzanthrone (BA) and 3-bromobenzanthrone (3-BBA) are important dye intermediates used in the manufacture of various vat and disperse dyes. BA has been implicated as a cause of hepatic malfunctions and dermal lesions in workers. However, not much information on halogenated BAs, especially 3-BBA, is available. Experiments were designed to undertake a comparative safety assessment of both BA and 3-BBA, given orally at a dose of 50 mg/kg body weight for 10 days to guinea pigs. There was a significant decrease (25%) in body weight with 3-BBA, whereas BA treatment did not cause any change. Serum glutamate oxaloacetate transaminase and glutamate pyruvate transminase were found to be significantly (P<0.05) increased in 3-BBA- as well as in BA-treated animals. 3-BBA and BA led to substantial depletion of ascorbic acid in both liver and adrenal glands. However, depletion of ascorbic acid was more pronounced with 3-BBA (19.2-28.3%) than with BA (13.5-16.6%). 3-BBA and BA treatments caused 80% and 24% depletion of hepatic free sulfydryl content, while lipid peroxidation showed a significant enhancement of 73% and 47%, respectively. BA and 3-BBA caused decreases in cytochrome P-450 content and phase I enzymes particularly ethoxyresorufin- O-deethylase and aryl hydrocarbon hydroxylase, whereas phase II enzymes (quinone reductase and glutathione- S-transferase) were substantially increased. Activities of bio-antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase, were significantly increased by 153, 104, 20 and 67% in the 3-BBA-treated group, whereas the degree of increase in these parameters was relatively less in BA-treated group. The data indicate that both BA and 3-BBA can disturb membrane integrity by decreasing endogenous glutathione and ascorbic acid levels with a concomitant increase in lipid peroxidative damage. This may in turn lead to impairment of hepatic P-450-dependent monooxygenase, while the changes in antioxidant enzymes reveal oxidative stress. 3-BBA treatment caused dilation of portal triad with thickening of arterial wall, hyperplasia of Kupffer cells and influx of inflammatory cells between hepatic cords, which could be due to formation of Br(*) radical or due to formation of semiquinone type of intermediate following oxidation. The results may be interpreted to mean that industrial workers exposed to 3-BBA are at higher risk than those exposed to BA, and necessary precautions should be taken to safeguard their exposure risks.
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PMID:Comparative effect of benzanthrone and 3-bromobenzanthrone on hepatic xenobiotic metabolism and anti-oxidative defense system in guinea pigs. 1259 Mar 61

The effects of aqueous Azadirachta indica leaf extract (AAILE) on benzo(a)pyrene [B(a)P]-induced forestomach tumorigenesis, B(a)P-DNA adduct formation and certain parameters of carcinogen biotransformation system in mice have been reported earlier from our laboratory. In this study, the effects of AAILE on the enzymes of B(a)P biotransformation, which play crucial role in initiation of chemical carcinogenesis - aryl hydrocarbon hydroxylase (AHH) and uridinediphosphoglucuronosyltransferase (UDP-glucuronosyltransferase) have been evaluated in murine forestomach and liver. In addition, lipid peroxidation (LPO) levels in forestomach as well as liver and the activities of tissue injury marker enzymes - lactate dehydrogenase, aspartate aminotransferase and alkaline phosphatase in the serum have also been evaluated. Oral administration of AAILE (100 mg/kg body wt for 2 weeks) reduces the AHH activity and enhances the UDP-glucuronosyltransferase activity in both the tissues, suggesting its potential in decreasing the activation and increasing the detoxification of carcinogens. The LPO levels decrease upon AAILE treatment in the hepatic tissue, suggesting its antioxidative and hence anti-carcinogenic effects. Non-significant alterations have been observed in tissue injury marker enzymes upon AAILE treatment, suggesting its safety at the given dose. In conclusion, AAILE appears to modulate initiation phase of carcinogenesis and may be suggested as safe and an effective agent for chemoprevention.
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PMID:Azadirachta indica leaf extract modulates initiation phase of murine forestomach tumorigenesis. 1797 Feb 78