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)

Aqueous extracts of the seeds of Nigella sativa and mature leaves of Dregea volubilis were administered orally under light ether anaesthesia to male Sprague-Dawley rats for 14 days. Key hepatic enzyme concentrations and histopathological changes in the liver in both treatment groups at the end of 14 days were compared with a control group which received distilled water under identical conditions for 30 days and with a group of normal animals. Serum gamma-glutamyl transferase concentrations were significantly increased in both extract groups while serum alkaline phosphatase concentrations were significantly increased following administration of only D. volubilis when compared with either the control or the normal group. Serum alanine aminotransferase concentrations were significantly increased in both extract groups when compared with the normal group but not with the control group. Degenerative changes in hepatocytes were seen following administration of D. volubilis while consistent significant histopathological changes were not evident following administration of N. sativa.
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PMID:Possible hepatotoxicity of Nigella sativa seeds and Dregea volubilis leaves. 167 78

Dose- and time-related effects of Cd (II) (0.5 or 1.0 mg/kg, Cd as CdCl2.H2O, subcutaneously, daily for 48 h, 1, 3, or 6 wk) were investigated in rats. A dose-related increase in the activity of plasma alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate aminotransferase (GOT), and alanine aminotransferase (GPT) was evident only at 6 wk, whereas an early rise in ALP and LDH was seen at 3 wk in 1.0 mg Cd group only. The hepatic and renal metallothionein (MT) induction displayed a dose- as well as time-related increase with Cd accumulation. A significant increase in hepatic Zn and renal Cu, no change in hepatic Cu, and a slight increase in renal Zn was observed. Urinary ALP and leucine aminopeptidase (LAP) showed an initial increase at 48 h, thereafter returned to near normal. A second phase of enzymuria (ALP, LAP, GOT, GPT, gamma-glutamyl transpeptidase), proteinuria, and aminoaciduria occurred at 6 wk in a dose-related manner. The urinary excretion of specific renal enzymes appeared closely related to the MT induction and organ Cd levels.
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PMID:Biochemical response to cadmium. Dose-time effect. 171 72

Rats were pretreated with a single iv dose of chlorpromazine (CPZ) 3 mg/kg, verapamil 1 mg/kg, or quinacrine 2 mg/kg. Livers were taken out and perfused with University of Wisconsin (UW) preservation solution and stored on ice for 48 h in the UW solution before reperfusion with erythrocyte-free and colloid-free Krebs-Hanseleit buffer at 38 degrees C in a nonrecirculating perfusion system for 2 h. CPZ- and quinacrine-pretreated livers produced significantly more bile than control livers and also released significantly less alanine aminotransferase into the perfusate at 30, 60, and 120 min of reperfusion. Aspartate aminotransferase levels were lower at 30 and 60 min of reperfusion for CPZ-pretreated livers but not at 120 min. The only difference between groups concerning lactate dehydrogenase (LDH) release into the perfusate was that CPZ decreased the amount of LDH released at 60 min. Total tissue water or tissue electrolyte content of the liver tissue at the end of the reperfusion did not differ between groups. In conclusion, verapamil was ineffective when given as single dose iv pretreatment to the liver donor but pretreatment with CPZ or quinacrine appeared to improve the function of the preserved liver.
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PMID:Chlorpromazine, quinacrine, and verapamil as donor pretreatment in liver preservation, tested in the isolated perfused rat liver. 175 29

Twenty adult male rats per group in 4 treatment groups were injected intraperitoneally at 08.00 hours with 0.1 ml of an aqueous cotton seed extract (Gossypium barbadense Linn.) (Malvaceae) in concentrations of (a) 105.25, (b) 21.21, (c) 4.65, (d) 2.325 mg ml-1 (kg body weight)-1, respectively. A fifth group (control) was given 0.1 ml of pyrogen free distilled water per rat. Five rats per treatment group were sacrificed at 2, 8, 24 and 168 hours respectively after treatment. Plasma follicle stimulating hormone (FSH) and luteinizing hormone (LH) showed no change. Plasma testosterone was lower (p less than 0.05) than that of control at 2 and 8 hours, with recovery by 168 hours post treatment. Plasma creatinine was raised by 2 hours, with recovery by 8 hours. Plasma urea rose gradually but persistently to a maximum of 168 hours. Plasma aspartate (AST) and alanine (ALT) transaminases were significantly higher (p less than 0.001) than that of controls throughout the study. Testicular histology showed early germ cell disorganization followed by progressive fibrosis (sperm cytoskeleton) by 24 hours. There was evidence of recovery by 168 hours. It is concluded that aqueous extract of cotton seed meal contains substances that can rapidly cause damage to testicular, liver, kidney and muscular tissues.
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PMID:Effects of an aqueous extract of cotton seed (Gossypium barbadense Linn.) on adult male rats. 177 60

The photocoagulating properties of the water-jet-cooled Nd:YAG laser (1,064 nm) have been studied in a rat tumor model. A colon carcinoma CC531 was implanted in the liver; 20 days after inoculation, laser therapy was performed with 600 J, 850 J, 1,200 J, 1,700 J, or 2,400 J at a power setting of either 10 or 20 W. Liver damage was determined in tissue specimen on day 1 after treatment and by serum levels of alanine aminotransferase and aspartate aminotransferase on day 1 and 2. Tissue specimen of day 36 were used to evaluate tumor remission. Liver function was assessed by antipyrine clearance on day 2. Light microscopic examination on day 1 showed coagulative necrosis up to 10 mm in diameter at 1,700 J and 20 W. At 20 W, liver damage was 22% larger than at 10 W (P = 0.0001). A significant relationship was found between laser energy and liver damage with complete tumor destruction in all animals at 2,400 J. No deterioration in liver function was found. The results of this study show the ability of the water-jet-cooled Nd:YAG laser to produce tumor coagulation necrosis with minor liver damage.
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PMID:Water-jet-cooled Nd:YAG laser coagulation: selective destruction of rat liver metastases. 181 80

1. The effects of nitrates and nitrites on growth, erythrocytic count, liver and kidney functions, humoral and cell mediated immune responses in cockerels were investigated. 2. Sodium nitrate (4.2 g/kg diet) and sodium nitrite (1.7 g/kg) retarded growth, caused methaemoglobinaemia and changes in erythrocytic count, serum concentrations of glutamic-pyruvic transaminase, creatinine and urea. 3. Cockerels given nitrate or nitrite in the food had reduced haemagglutination responses after injection of sheep erythrocytes and a reduced delayed hypersensitivity reaction to purified protein derivative tuberculin following sensitisation to Bacille Calmette Guerin. 4. Nitrates and nitrites are environmental pollutants present in food and water and they may contribute to the aetiology of liver and kidney diseases and problems related to failure of immunity in domestic fowls.
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PMID:Pharmacotoxicological aspects of nitrate and nitrite in domestic fowls. 186 78

The erythrocyte alanine aminotransferase (E-ALAT) activity with and without in vitro stimulation by pyridoxal phosphate of 60 healthy adolescents was measured before and after 6 weeks of supplementation with different water-soluble vitamins. The subjects who were divided into six groups received placebo (lactose tablets), pyridoxine, pyridoxine + ascorbic acid, pyridoxine + iron, pyridoxine + riboflavin and multivitamin supplements, respectively. Presupplementation E-ALAT activity increased significantly (p less than 0.05) for all supplemented subjects after 6 weeks. Deficient subjects (E-ALAT) index less than 1.16) however failed to respond to a combination of pyridoxine + ascorbic acid or multivitamins. It is suggested that pyridoxine in multivitamin preparations must exceed 1 mg to produce any useful improvement in vitamin B6 status of adolescents on suboptimal vitamin B6 intakes.
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PMID:Effect of supplementation with water-soluble vitamins on erythrocyte alanine aminotransferase activity of healthy adolescents. 187 96

Previous studies have demonstrated that various compounds, including the common groundwater contaminants trichloroethylene (TCE) and chloroform (CHCl3), can produce a synergistic toxic response when coadministered with the model hepatotoxicant carbon tetrachloride (CCl4). This phenomenon has not, however, been demonstrated following administration of these compounds in drinking water. Initial experiments indicated that Fischer 344 (F-344) rats were significantly more sensitive to these effects than the more commonly utilized Sprague-Dawley strain. To establish the suitability of this strain as a model, a variety of indicators of hepatotoxicity was evaluated and compared to histological evidence of injury 24 hr after dosing with CCl4 or a combination of CCl4 + TCE. Plasma alanine aminotransferase (ALT) activity was the most reliable indicator of hepatic injury and was well-correlated with the histologic data. Dose-response studies utilizing simultaneous ip dosing confirm the sensitivity of the F-344 rat, demonstrating synergistic toxicity at doses as low as 0.165 mmol/kg of CCl4 and 0.6 mmol/kg of TCE. Synergism was also detected following simultaneous ip administration of 1 mmol/kg CCl4 and 0.5 mmol/kg of CHCl3. To evaluate the effects of drinking water exposure, rats were pretreated for 3 days with solutions containing TCE (0-40 mM) or CHCl3 (0-8 mM) stabilized with 1% Emulphor (EL-620P) as their only source of fluids. A single, ip dose of CCl4 (1 mmol/kg) was then administered and 24 hr later animals were killed for examination of liver histology and determination of ALT activity. Although none of the pretreatments were detectably hepatoxic, rats which drank 15 and 40 mM TCE or 8 mM CHCl3 exhibited an enhanced response to CCl4.
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PMID:Pretreatment with drinking water solutions containing trichloroethylene or chloroform enhances the hepatotoxicity of carbon tetrachloride in Fischer 344 rats. 188 17

Ten- and ninety-day toxicity studies of 1,2-dichlorobenzene (DCB) were conducted in male and female Sprague-Dawley rats to meet the needs of the U.S. Environmental Protection Agency for toxicity data on this chemical for use in their determination of possible health risks related to human exposure. 1,2-Dichlorobenzene was administered at doses of 37.5, 75, 150, and 300 mg/kg/day (10-day), and 25, 100, and 400 mg/kg/day (90-day) in corn oil by oral gavage; control animals received corn oil. At time of sacrifice, gross necropsies were performed and selected tissues were weighed and prepared for histological evaluation. Blood was taken for hematology and clinical chemistries. In the 10-day study, exposure of 300 mg DCB/kg body weight to male rats resulted in a statistically significant decrease in final body weight, organ weights (heart, kidneys, spleen, testes, and thymus), and relative organ weights (spleen and thymus). A significant increase in absolute and relative liver weights was also noted in this dose group. Males also displayed significant increases in water consumption (300 mg/kg group), ALT (300 mg/kg) and leukocyte count (150 and 300 mg/kg). A significant increase in the incidence of hepatocellular necrosis was seen in the 300 mg/kg group of males compared to controls. In the 90-day study, male rats exposed to 400 mg DCB/kg displayed a statistically significant decrease in body weight, organ weight (spleen), and relative organ weight (spleen). The absolute weights of kidney and liver and the relative weights for heart, kidney, liver, lung, brain, and testes were increased significantly for this dose group. The absolute and relative weights of both the kidney and liver were significantly increased in the female 400 mg/kg dose group. The only clinical chemistry parameters statistically different than control were increased ALT (100 and 400 mg/kg groups), BUN and total bilirubin in the male 400 mg/kg group and total bilirubin in the 400 mg/kg female group. Histopathological evaluation showed hepatocellular lesions associated with DCB treatment which included centrolobular degeneration and hypertrophy, and single cell necrosis in male and females receiving 400 mg DCB/kg. The NOAEL observed in this study is 25 mg/kg/day.
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PMID:Ten- and ninety-day toxicity studies of 1,2-dichlorobenzene administered by oral gavage to Sprague-Dawley rats. 188 79

Antimony potassium tartrate (APT) is a complex salt that until recently was used worldwide as an antischistosomal drug. Treatment was efficacious only if APT was administered intravenously to humans at a near lethal total dose of 36 mg/kg. Because unconfirmed epidemiologic studies suggested there might be an association between APT treatment and bladder cancer, we initiated prechronic toxicity studies with the drug to select a route of administration and doses in the event that chronic studies of APT were needed. The toxicity and concentration of tissue antimony levels were compared in 14-d studies with F344 rats and B6C3F1 mice administered APT in the drinking water or by ip injection to determine the most appropriate route for longer term studies. Drinking water doses estimated by water consumption were 0, 16, 28, 59, 94 and 168 mg/kg in rats and 0, 59, 98, 174, 273, and 407 mg/kg in mice. APT was poorly absorbed and relatively nontoxic orally, whereas ip administration of the drug caused mortality, body weight decrements, and lesions in the liver and kidney at doses about one order of magnitude below those in drinking water. Because of these data and the dose-related accumulation of antimony in the target organs, an ip dose regimen was selected for subsequent studies. Both sexes of F344 rats and B6C3F1 mice were given 0, 1.5, 3, 6, 12, and 24 mg/kg doses of APT every other day for 90 d by ip injection. There were no clinical signs of toxicity nor gross or microscopic lesions in mice that could be attributed to toxicity of APT, although elevated concentrations of antimony were detected in the liver and spleen of mice. Rats were more sensitive than mice to the toxic effects of APT, exhibiting dose-related mortality, body weight decrements, and hepatotoxicity. The concentrations of antimony measured in liver, blood, kidney, spleen, and heart of rats were proportional to dose, but there were no biochemical changes indicative of toxicity except in the liver. Hepatocellular degeneration and necrosis occurred in association with dose-related elevations in activities of the liver-specific serum enzymes sorbitol dehydrogenase and alanine aminotransferase. By alternating the site of abdominal injection and the days of treatment, mesenteric inflammation at the site of administration was minimized in the rats and mice, indicating that the ip route would be suitable for chronic studies.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparative toxicity and tissue distribution of antimony potassium tartrate in rats and mice dosed by drinking water or intraperitoneal injection. 189 Jun 93


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