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)

Nineteen weanling ponies and 1 adult pony were given a single oral dose of aflatoxin B1 (AFB1). Dosages were: 0, 0.5, 1, 2, 4, 5, 6, and 7.4 mg of AFB1/kg of body weight. Vital signs were monitored, and whole blood and serum collected for analysis of serum enzymes, prothrombin time, blood cell counts, and serum urea nitrogen. Ponies that died were examined for gross lesions, and tissues were collected for histopathologic examination and analysis of AFB1 and AFM1 residues. Two of the 4 ponies given the 2 mg/kg dose and all ponies given the larger dosages died within 76 hours. Clinical signs included increased rectal temperature, faster heart and respiratory rates, abdominal straining, bloody feces, and tetanic convulsions. At necropsy, ponies that died of acute aflatoxicosis showed visceral petechiae and hepatic focal lesions. Histopathologic changes included severe hepatic necrosis, vacuolation, and bile duct hyperplasia. Aflatoxins B1 and M1 were recovered from liver, kidney, skeletal muscle, and gastrointestinal contents. One other pony given the 2 mg/kg dose died 32 days after dosing, and 1 control pony died after 70 days. Continuous elevations in prothrombin time and serum aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase levels were observed in ponies dosed at 4 mg/kg or more. Significant (P less than 0.05) elevations in these values, which peaked 2 to 3 days after dosing, were seen in ponies given the 2 mg/kg dose. This group also had significant increases over controls in PCV and hemoglobin concentration 5 days after dosing.
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PMID:Acute experimentally induced aflatoxicosis in the weanling pony. 613 67

The effects of chronic intra-peritoneal administration of aflatoxin B1 on the activity of alkaline and acid phosphatases; glutamic oxaloacetate (GOT) and pyruvate transaminases (GPT); 5'-nucleotidase and lactic dehydrogenase enzymes were monitored in the testis and kidney of adult albino rats. Results showed that aflatoxin B1 depressed the activity of alkaline phosphatase in both tissues, but increased that of acid phosphatase in only the testis. While GOT and 5'-nucleotidase were inhibited, GPT and lactic dehydrogenase activity was enhanced by this carcinogen. These responses were similar for the testis and kidney. The above findings coupled with the microscopical observation of the testis tissue seem to indicate that the essential lesion of this toxin on the testis may be a modification of the enzymes of germinal cells resulting from a gradual depletion of the latter. Furthermore, the results appear to show that by and large, aflatoxin B1 exerts only slightly different effects on the testis and kidney at the enzyme level.
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PMID:The effects of aflatoxin B1 on some testicular and kidney enzyme activity in rat. 625 8

Groups of 8 male crossbreed domestic goats were given 3 dosage levels of aflatoxin B1 [(AFB1) mg/kg of body weight/day] orally: 0.1 for 34 days; 0.2 for 18 days; or 0.4 for 10 days. Clinical condition, feed consumption, and selected blood values were determined. Clinical signs of toxicosis included decreased feed consumption, slight-to-moderate loss of body weight, mucopurulent nasal discharge, dyspnea, coughing, lethargy, icterus, diarrhea (4 goats), and subnormal body temperature 24 to 48 hours before death. Clinicopathologic changes included increases in total RBC count, PCV, hemoglobin concentration, serum bilirubin concentration, and serum activities of aspartate aminotransferase, isocitric dehydrogenase, and ornithine carbamyl transferase. Goats given the 2 smaller dosage levels of AFB1 had slight increases of serum total protein (TP) concentration compared with control goats, but goats given the larger dosage levels of AFB1 initially had a slight decrease in TP. Aflatoxin had little effect on total WBC count. Serum alanine aminotransferase (ALT) activities in goats given the 2 larger dosage levels of AFB1 were similar to those of control goats, but goats given the smallest dosage level of AFB1 had increased serum ALT activities. Aflatoxin did not produce consistent dose-related changes in serum alkaline phosphatase activities. Seemingly, goats are susceptible to aflatoxin. Onset of clinical signs was dose-related. Onset and magnitude of increases in PCV, hemoglobin concentration, serum bilirubin concentration, and activities of serum aspartate aminotransferase, ornithine carbamyl transferase, and isocitric dehydrogenase were dose-related. Changes in TP and activities of serum ALT and alkaline phosphatase were neither dose-related nor were they potentially useful indicators of toxicosis.
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PMID:Caprine aflatoxicosis: experimental disease and clinical pathologic changes. 643 Jan 34

Male New Zealand White rabbits were orally given 0.05 mg of aflatoxin B1 (AFB1)/kg of body weight daily for 10 days and were treated with glutathione-precursors and depletor, antibacterial agents, or sodium thiosulfate. The drug administered, the mortality, and the mean survival time were as follows: corn-oil controls (0), euthanatized at 25 days; AFB1-controls (2), 21 days; AFB1 and saline controls (2), 22 days; cysteine and AFB1 (5), 13 days; methionine and AFB1 (5), 12 days; sodium thiosulfate and AFB1 (2), 21 days; sulfadimethoxine and AFB1 (1), 24 days; oxytetracycline and AFB1 (0), euthanatized at 25 days; and ethyl maleate and AFB1 (3), 21 days. Clinical signs of toxicosis included decreased feed consumption during AFB1 administration, loss of body weight or failure to gain, and death. Clinicopathologic changes included increases in serum bilirubin concentration and alanine aminotransferase and aspartate aminotransferase activities. Prothrombin and activated partial thromboplastin times were lengthened. Plasma fibrinogen concentration was decreased. Changes in PCV, hemoglobin concentration, and serum alkaline phosphatase were unremarkable. Oxytetracycline had protective effects against chronic aflatoxicosis in rabbits. Cysteine and methionine enhanced chronic aflatoxicosis.
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PMID:Effects of various treatments on induced chronic aflatoxicosis in rabbits. 680 40

Hepatotoxicity of aflatoxin B1 (2.0 and 4.0 mg/kg i.p.) as determined by plasma enzyme activities (GPT and GOT), liver triglycerides and histopathologic changes was enhanced in rats pretreated with four oral doses of ethanol (4.0 g/kg each) at 48, 45, 24 and 21 hrs prior to aflatoxin B1 administration. Pretreatment with ethanol (4.0 g/kg) slightly increased liver weight without changing hepatic microsomal protein contents. Also it caused an increase in microsomal aniline hydroxylase but a decrease in p-nitroanisole-o-demethylase, 48 hrs after the first ethanol dose. In the rats pretreated with ethanol, aflatoxin B1 was metabolized at a higher extent to aflatoxins M1 and Q1. These results suggest that an increased hepatotoxicity of aflatoxin B1 after pretreatment with ethanol may presumably due to an increase in microsomal formation of active aflatoxin B1 metabolite.
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PMID:Enhanced hepatotoxicity of aflatoxin B1 by pretreatment of rats with ethanol. 681 83

Thirteen biochemical parameters (viz. glucose, calcium, inorganic phosphorous, urea nitrogen, uric acid, cholesterol, albumin, total protein, total bilirubin, alkaline phosphatase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase) were determined in serum and partly in liver of rats 1-28 days after i.p. aflatoxin B1 (AFB) (3 mg/kg). Histological examinations of the liver were also made in parallel to the biochemical studies. In the serum, enzyme activities and total bilirubin level increased and peaked on the 2nd day, while other activities of aspartate aminotransferase and alanine aminotransferase in the liver significantly decreased and reached a minimum on the 2nd day after AFB administration. The depression of the liver enzyme activities persisted over 7 days. The liver protein content also reduced transiently during 1-1.5 days. However, all biochemical parameters returned to normal levels 2 weeks after treatment, and remained so throughout the rest of experimental period. Histological changes in the liver were very similar to those reported by other.
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PMID:Sequential biochemical and histological changes in rats treated with aflatoxin B1. 742 38

The relative contribution of, and possible mechanism of interaction between, aflatoxin and hepatitis B virus (HBV) in the development of primary hepatocellular carcinoma can be better investigated now that markers of individual exposure to both factors are available. In this study, blood samples were collected over a 1-month period from 117 children aged 3 to 4 years, resident in Kuntair or Kerr Cherno in the Upper Niumi District of The Gambia. Samples were analyzed for aflatoxin-albumin (AF-alb) adducts, markers of HBV infection, liver enzymes [serum alanine aminotransferase (ALT)] as markers of liver damage, and glutathione S-transferase M1 genotype. All but two children showed detectable serum AF-alb with levels ranging from 2.2 to 250.4 pg aflatoxin B1-lysine equivalent/mg albumin. There was a significant positive correlation between AF-alb and ALT (r = 0.4; P < 0.001). HBV carriers showed moderately higher levels of AF-alb than noncarriers but the difference was not statistically significant and the association between AF-alb and ALT was unchanged when the HBV carriers were excluded from the analysis, suggesting that factors other than HBV infection contributed to the association. The null glutathione S-transferase M1 genotype was infrequent (17.7%) in this population and was not associated with any difference in AF-alb adduct levels compared to glutathione S-transferase M1-positive individuals. However, the percentage of individuals with the null genotype varied significantly between ethnic groups with 32.1% in Fula, 8.8% in Mandinka, and 13.3% in Wollof.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aflatoxin, liver enzymes, and hepatitis B virus infection in Gambian children. 826 73

Dithiolethiones are an important class of cancer chemopreventive agents. More than 50 new dithiolethione analogs were synthesized for structure-activity studies. Using selected dithiolethiones, studies were designed to measure protection against the hepatotoxicity of aflatoxin B1 (AFB1) and relate it to the protection against carcinogenicity. Young male F344 rats were pretreated with 0.1 or 0.3 mmol dithiolethiones/kg body wt and challenged with toxic doses of AFB1 (50 micrograms/100 g rat/day) on 2 successive days. One day later, the protection from hepatotoxicity was assessed by measuring serum hepatic enzymes, hepatic necrosis, and degree of bile duct cell proliferation. The ability of these dithiolethiones to prevent AFB1-induced tumorigenicity was assessed by quantifying the hepatic burden of putative preneoplastic lesions [placental glutathione S-transferase (GST-P)-positive foci]. Significant correlations (p < 0.01) were observed between these toxicological indices and GST-P focal burden (alanine aminotransferase, r = 0.943; sorbitol dehydrogenase, r = 0.897; histological index, r = 0.893; bile duct cell proliferation, r = 0.933). These results imply that inhibition of hepatotoxicity affords protection against hepatocarcinogenicity. The extent of protection from acute hepatotoxicity offers a simple, short-term biological endpoint to screen dithiolethiones and related compounds for their chemopreventive properties.
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PMID:Protection against aflatoxin B1-induced hepatic toxicity as short-term screen of cancer chemopreventive dithiolethiones. 892 28

1. Thonningia sanguinea, a plant used prophylactically against bronchial asthma in Ghana was recently found to have antioxidative and hepatoprotective actions in our laboratory. 2. In this study, the effect of T. sanguinea extract on certain biochemical indices in serum and liver of Fischer 344 rats given a single intraperitoneal (i.p.) dose (1 mg/kg) of aflatoxin B1 (AFB1) was investigated. 3. Administration of AFB1 resulted in significant increases in serum alanine aminotransferase (ALT) and glutathione S-transferase (GST) levels and a significant decrease in aniline hydroxylase activity in liver microsomes. When T. sanguinea (5 ml/kg) was intraperitoneally administered to rats 12 h and 1 h before AFB1, liver injury was significantly reduced as seen in the decreased levels of serum ALT and serum GST. However, the decrease in aniline hydroxylase activity by AFB1 was not recovered but enhanced by T. sanguinea pre-treatment. 4. Kinetic analysis of cytochrome P450 activity of rat liver microsomes in vitro demonstrated that T. sanguinea inhibited aniline hydroxylase non-competitively suggesting depression of biotransformation of AFB1 to toxic metabolites. 5. The data indicate a hepatoprotective action of T. sanguinea against AFB1-induced liver injury.
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PMID:Medicinal herb, Thonningia sanguinea protects against aflatoxin B1 acute hepatotoxicity in Fischer 344 rats. 975 33

2-(Allylthio)pyrazine (2-AP), a synthetic organosulfur compound, exhibits hepatoprotective and chemopreventive effects. The effects of 2-AP on aflatoxin B1 (AFB1)-induced hepatotoxicity was studied in rats. 2-AP treatment substantially reduced AFB1-induced toxicity, as evidenced by reduction in the mortality rate of animals as well as decreases in serum alanine aminotransferase and sorbitol dehydrogenase activities. AFB -induced lipid peroxidation was also significantly reduced in rats by 2-AP treatment. Studies were extended to determine whether 2-AP was active in inhibiting cytochrome P450-mediated metabolic activation of AFB1. Covalent binding of AFB1 to calf thymus DNA in the presence of S-9 fraction was inhibited by 2-AP in vitro. Hepatic microsomal pentoxyresorufin-O-depentylase and ethoxyresorufin-O-deethylase activities were also potently inhibited by 2-AP. These results demonstrated that 2-AP was effective in protecting the liver against AFB1-induced toxicity and the mechanism of chemoprotection by 2-AP might involve inhibition of the P450 2B- and 3A2-mediated metabolism of AFB1.
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PMID:2-(allylthio)pyrazine inhibition of aflatoxin B1-induced hepatotoxicity in rats: inhibition of cytochrome P450 2B- and 3A2-mediated bioactivation. 992 Mar 47


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