Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

No significant increases in serum SDH, ALT and AST activities were observed in goats and rats receiving oral sulfadimethoxine at 5 times the therapeutic dose. The quail showed significantly higher activities of SDH and ALT when compared to control values. Moderate increases in liver microsomal cytochrome P-450 and aniline hydroxylase activity were observed in goats and quail but no appreciable change in benzphetamine N-demethylase activity was detected in any species. These results suggest a lack of hepatic toxicity of sulfadimethoxine to these species under the reported experimental conditions.
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PMID:Studies on possible sulfadimethoxine toxicity to liver and liver drug metabolizing enzyme system of goats, quail and rats. 327 41

Three housed North Ronaldsay sheep were treated with copper in the form of cupric oxide "needles", two at the manufacturer's recommended dosage rate and the third at twice this level. Sheep of this breed are especially sensitive to high dietary intake of copper. Pre- and post-dosing blood samples were monitored for changes in packed cell volume and changes in content of plasma copper, bilirubin, AST and SDH. Weight changes were also recorded. The animal dosed at twice the recommended level died on day 19 post-dosing of acute copper poisoning. The two dosed at the standard rate remained healthy and put on weight steadily throughout the six months following treatment. Two Welsh Mountain sheep dosed at the standard rate and maintained and examined in the same way likewise showed no signs of copper toxicity.
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PMID:Susceptibility of North Ronaldsay sheep to copper from cupric oxide needles. 397 74

Toxicity of the antioxidant dodecyl gallate was studied in 150-day experiments on male white rats. The antioxidant was administered intragastrically in doses of 250, 50 and 10 mg/kg bw. The general status and behavior of the animals, the survival rate, weight gain, peripheral blood, the amount of urea, total serum protein, soluble proteins of the liver and kidneys, and activity of enzymes (AST, ALT, LDH, SDH, glucose-6-phosphate dehydrogenase, alkaline and acid phosphatase of the serum, liver and kidneys, the weight of the internal organs) were studied over time, followed by morbid anatomy studies. Quantitative determination of serum lipids (total fats, total cholesterol, esterified cholesterol, free cholesterol, triglycerides, free fatty acids, triglycerides plus free fatty acids, and phospholipids) was made on the 150th day after the onset of experiments. When administered in a dose of 250 mg/kg, dodecyl gallate produced death of the animals and an increase in the content of triglycerides plus free fatty acids, a decrease in the weight of the spleen and morphological alterations in the liver, kidneys and spleen. The dose 50 mg/kg was also toxic. It brought about changes in the activity of serum and liver AST, an increase in the content of TF, TG, FFA, TG plus FFA and phospholipids, a reduction in the weight of the spleen and pathological changes in the liver, kidneys and spleen. The dose 10 mg/kg is regarded as liminal.
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PMID:[Toxicological study of the long-term effects of the antioxidant dodecyl gallate on albino rats]. 400 81

1. The acute oral LD50 and chronic LC50 toxicity values for ethylene dibromide (EDB) were estimated for japanese quail. 2. Single sub-acute oral and intraperitoneal doses of EDB (1/2 LD50) and chronic oral doses of EDB (1/3 LC50) were administered to quail in order to characterise the sub-lethal effects of EDB residues. 3. At 24 h after sub-acute dosing, relative liver weight, plasma aspartate aminotransferase (AT) [EC 2.6.1.1] and L-iditol (sorbitol) dehydrogenase (SDH) [EC 1.1.1.14] were elevated and decreases were found in hepatic total lipid, total protein, AT and glutamic dehydrogenase (NAD (P)+) (GDH) and plasma cholinesterase (ChE) [EC 3.1.1.8] and total lipid. 4. Following chronic administration, elevations in relative liver weight, plasma ChE and total lipid, haemoglobin and haematocrit were found and hepatic AT, GDH and total lipid were decreased. 5. The changes in hepatic and plasma enzymes and constituents are discussed in relation to possible biphasic effects resulting from EDB exposure.
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PMID:A study on the toxicity and the biochemical effects of ethylene dibromide in the Japanese quail. 702 16

Liver and kidney injury following acute or chronic exposure to cadmium is well characterized. While hepatocytes and endothelial cells of the sinusoids are thought to be the primary cellular targets in the liver, ultrastructural changes may vary depending upon the exposure regimen and the time following administration. Since acute and chronic liver disease is often associated with the presence of cytokines, we investigated the role of proinflammatory cytokines in cadmium-induced hepatotoxicity. Supernatants from cultured liver slices obtained from acute or subchronic cadmium-exposed rats and mice were collected and cytokine secretion was examined. In addition, mRNA transcripts for IL-1 alpha, IL-1 beta, IL-6, TNF-alpha, MIP-2, IFN-gamma, and ICAM-1 from livers of treated mice were quantitated by reverse transcription-polymerase chain reaction. Modest increases in secretion of TNF-alpha, IL-1 alpha, and IL-6 were observed in response to cadmium which were enhanced in LPS-primed mice. Additionally, cadmium exposure increased IL-1 alpha, IL-1 beta, TNF-alpha, MIP-2, IL-6, and ICAM-1 mRNA transcripts in the liver. Immunohistochemical analysis revealed that TNF-alpha was associated with nonparenchymal cells in livers of cadmium-treated mice. Cadmium exposure produced a marked increase in plasma hepatocellular enzyme levels (i.e., AST, LDH, SDH), acute phase proteins (i.e., serum amyloid A), and foci formation in the liver, while focal inflammation and serum amyloid A (SAA) secretion, but not plasma enzymes, were further increased in cadmium-exposed mice primed with LPS. SAA secretion and focal inflammation were prevented by pretreatment with antibodies to TNF-alpha, indicating that these pathological manifestations are cytokine dependent. These data indicate that TNF-alpha, released from nonparenchymal cells as well as associated cytokines, are responsible for certain manifestations observed with cadmium-induced hepatotoxicity.
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PMID:Role of tumor necrosis factor-alpha in cadmium-induced hepatotoxicity. 753 60

Liver and muscle amino acid enzyme activities and plasma proteins, urea, amino acids, glucose, lactate, 3-hydroxybutyrate and acetoacetate concentrations were studied in growing rats undergoing adaptation to high-fat, high-energy diet and glucose gavage. Liver and muscle were used for the estimation of alanine transaminase (GPT, EC 2.6.1.1.), adenylate deaminase (AMD, EC 3.5.4.6.), glutamine synthetase (GST, EC 6.3.1.2) and serine dehydratase (SDH, EC 4.2.1.13) activities, the latter only in liver samples. The most important modifications produced in muscle enzyme activities by glucose gavage were observed in rats fed a cafeteria diet. Glucose gavage affects liver enzyme activities in the same sense than cafeteria diet. Energy plasma components were affected in opposite way by glucose gavage according to diet administered.
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PMID:Changes induced in amino acid-enzymes of developing rats by a high-energy diet and glucose gavage. 768 82

The carcinogenic water disinfection byproduct, bromodichloromethane (BDCM), produces renal and hepatic toxicity in rodents in acute and subchronic studies. In the present investigation, female rats and mice (n = 6) were dosed daily for 5 consecutive days with BDCM (dissolved in an aqueous, 10% Emulphor solution) by gavage. Rats received 75, 150 and 300 mg BDCM/kg body weight/day and mice received 75 and 150 mg BDCM/kg body weight/day. Two rats in the 300 mg/kg/day treatment group died on day 5. On day 6, the animals were sacrificed and serum samples were taken for analysis of indicators of hepatic and renal toxicity. Livers and kidneys were excised and samples taken for histopathological evaluation. Portions of the livers were also utilized to produce microsomes for analysis of cytochrome P450 enzyme activities and total P450 content. Total hepatic cytochrome P450 was decreased in rats dosed with 150 and 300 mg BDCM/kg body weight/day, but was not significantly affected in BDCM-treated mice. Serum lactate (LDH) and sorbitol (SDH) dehydrogenase, aspartate aminotransferase (AST), creatinine and blood urea nitrogen were increased above those of controls in rats dosed with 300 mg BDCM/kg/day. These data suggested that hepatic and renal damage had occurred in this treatment group. This was confirmed by histopathological analyses which revealed that lesions occurred in both hepatic and renal tissues from rats dosed with 150 and 300 mg BDCM/kg/day. The hepatic lesions were centrilobular and primarily consisted of vacuolar degeneration. The hepatotoxicity indicators alanine aminotransferase (ALT) and SDH were increased in mice dosed with 150 mg BDCM/kg/day. However, no histopathological lesions were observed in these animals. This study shows that BDCM is both hepatotoxic and nephrotoxic to female rats after repeated dosing, but is only weakly hepatotoxic to female mice at the administered doses. Also, reduced activities of hepatic cytochrome P450 were observed in rats, but not mice. These species differences in toxicity and xenobiotic metabolizing enzyme inhibition caused by BDCM suggest that an understanding of the mechanism of toxicity of this compound will be critical when extrapolating rodent toxicity data to humans for this environmental pollutant.
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PMID:Toxicity of bromodichloromethane in female rats and mice after repeated oral dosing. 780 27

Nine populations of Oncomelania, field-collected from Anhui, Shanghai, Jiangsu, Zhejiang, Jiangxi, Hunan, Hubei, Sichuan and Yunnan were studied by horizontal starch gel electrophoretic method with 24 enzyme systems (AAT, AcPH, AK, AO, APH, CK, EST, GDH, GPI, G6PD, HBD, ISDH, LAP, LDH, ME, MDH, MPI, NADD, OCT, PGM, 6PGD, SDH, SOD, XDH) analyzed. 40 loci and 117 alleles were detected in the Oncomelania. Both of GPI and PGM-I, with 7 alleles, were the most variable loci. 22 loci had more than 3 alleles each. Of 40 loci examined in the 24 isozyme systems, 14 were found to be polymorphic, the proportion of multilocus enzymes being 58.3%. Our results showed that the genetic polymorphism existing in the populations of Oncomelania in the mainland of China. PGM and MDH, were found in both the populations of Oncomelania and strains of Schistosoma japonicum in the mainland of China. The results provided a new idea for studying snails and Schistosoma. Also, we found that there might be some correlation between the polymorphic locus and the feature of the shell of Oncomelania snail.
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PMID:[Study on allele frequency in Oncomelania from the mainland of China]. 786 49

Coumarin is a known hepatotoxicant in laboratory animals, particularly rats. However, the mouse lung was identified as a major target organ in a chronic bioassay, with an oral gavage dosage of 200 mg/kg coumarin increasing the incidence of alveolar/bronchiolar adenomas and carcinomas. The purpose of the present work was to determine whether coumarin was acutely toxic in the mouse and rat lung. Male and female B6C3F1 mice were dosed orally by gavage with coumarin at 0, 10, 20, 50, 100, 150, and 200 mg/kg and lung toxicity was determined 24 h later by histological evaluation. The results indicated that coumarin dosages >/= 150 mg/kg caused selective injury to Clara cells in the distal bronchiolar epithelium. The time course of this injury was studied from 6 h to 7 days after a single dosage of coumarin (200 mg/kg). At 12 h after dosing, Clara cell swelling was apparent along with the onset of necrosis and bronchiolar epithelial disorganization. At 24-48 h, necrotic Clara cells were observed sloughed into the lumens of the terminal bronchioles, with concomitant thinning of the epithelium and flattening of the remaining ciliated cells. By 72-96 h, there was epithelial hypertrophy and hyperplasia, and by 7 days after dosing, the Clara cells had regenerated and the bronchiolar epithelial architecture appeared nearly normal. Unlike the mouse, oral administration of coumarin (200 mg/kg) caused severe hepatotoxicity in male F344 rats, seen histologically as centrilobular necrosis and associated with increases, up to 140-fold, in serum ALT, AST, and SDH levels. Clara cell toxicity was not observed in the distal bronchioles of treated rats. However, in the upper airways, coumarin treatment produced generalized epithelial necrosis involving both ciliated and nonciliated cells. 3,4-Dihydrocoumarin (DHC), which is not a mouse lung carcinogen, did not cause Clara cell injury when dosed to mice at 800 mg/kg. This finding suggests, because DHC lacks a 3,4-double bond, that bioactivation of coumarin to a 3,4-epoxide intermediate may contribute to mouse lung Clara cell toxicity. Collectively, the results indicate that coumarin is a Clara cell toxicant and establish the mouse lung as a target organ for coumarin toxicity. These new findings lay the foundation for studies to determine the mechanisms of coumarin-induced toxicity and carcincogenicity and to define the relevance of these effects to humans.
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PMID:Selective Clara cell injury in mouse lung following acute administration of coumarin. 970 86

The comparative effects of diazinon and malathion on Najdi sheep were described in sheep allotted as untreated controls, diazinon-treated at 25 mg/kg/d or 50 mg/kg/d, and malathion-treated at 25 mg/kg/d or 50 mg/kg/d. Although serum cholinesterase (ChE) activity was reduced, neither significant clinical signs nor severe pathological changes were produced in sheep dosed orally with 25 or 50 mg diazinon/kg/d for 21 d. Both oral dose levels of malathion were lethal to sheep between 1 and 6 d and caused, prior to death, hyperexcitability, tremors, clonic convulsions, salivation, nasal discharge, incoordination of movement, paresis of the limbs and recumbency. Lesions were widespread congestion and hemorrhage, patchy pulmonary cyanosis, gastroenteritis and hepatonephropathy. These changes were accompanied by increases in the activities of serum SDH and AST, in the concentrations of urea, triglyceride and cholesterol, and decreases in ChE activity and in RBC, PCV and Hb values.
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PMID:Comparative effects of diazinon and malathion in Najdi sheep. 1050 28


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