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)

Phagocytic activity as a function of the reticuloendothelial system (RES) has been studied in CCl4-induced liver injury by using the carbon clearance test. Liver damage in mice was induced by administration of 20% CCl4 in olive oil (p.o.). After a single administration of CCl4, significant increases in liver/body weight ratio, serum GOT and GPT levels, alpha, beta and gamma-globulins and BSP retention, and decreases in serum albumin, an activity of the hepaplastintest and the correct phagocytic activity, alpha value, were found. After 15 administrations of CCl4 (3 times a week), mild increases in serum GPT level and BSP retention and decreases in the activity of the hepaplastintest and both phagocytic indices, K and alpha values, were observed. However, zymosan treatment 3 days before sacrifice induced an increase in K value depressed by multiple administrations of CCl4. The depression of carbon uptake by Kupffer cells can be seen by light microscopy after multiple administrations of CCl4 compared with that of saline and olive oil. These findings indicate that the RES phagocytosis is suppressed more strongly in chronic liver injury by 15 CCl4 administrations than in acute injury by a single one, although the biochemical parameters indicating liver injury are shown to have an opposite tendency. A clear correlation between the alteration of RES activity and the degree of liver injury was not noted.
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PMID:Function of reticuloendothelial system on CCl4 induced liver injury in mice. 409 93

The toxicokinetic parameters of phenobarbital (PB) were assessed in a female rat model of liver disease. In a preliminary study to determine the optimum dose of DL-ethionine (ET) for creating liver damage, intraperitoneal injection of 250, 500, or 1,000 mg/kg of ET was done for 4 days. ET treatment caused an increase in serum GOT and GPT activity and a decrease in the serum glucose concentration. In the liver, triglycerides and free fatty acids were increased and glucose and S-adenosylmethionine (SAM) were decreased. Histologic examination revealed diffuse fatty degeneration of the hepatocytes. These findings accorded with those already reported as characteristic of ET intoxication. The toxicokinetic parameters for PB were determined after oral or intravenous administration of 100 mg/kg of PB to rats with ET (500 mg/kg, i.p.)-induced hepatotoxicity. After oral administration of PB, prolongation of the Tmax, increased AUC0-infinity, and decreased ke and CL values were noted in ET-treated rats. When PB was given intravenously, the AUC0-infinity was increased while the values of alpha, beta and CL were decreased. A high level of urinary excretion of PB persisted for 48 hr. Protein binding of PB was unchanged in ET-treated animals, but the extent of bioavailability of PB tended to increase. These results indicate that elimination of PB was impaired in the ET-treated rats.
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PMID:Toxicokinetics of phenobarbital in rats with DL-ethionine-induced liver injury. 829 28

BMS-189453 is a synthetic retinoid that acts as an antagonist at retinoic acid receptors alpha, beta, and gamma. In Sprague Dawley rats at daily oral doses of 15, 60, or 240 mg/kg for 1 month, BMS-189453 produced increases in leukocyte counts, alkaline phosphatase and alanine aminotransferase levels, and marked testicular degeneration and atrophy at all doses. Significant overt signs of toxicity and deaths occurred at 240 mg/kg, whereas body-weight and food-consumption decreases occurred at 60 and 240 mg/kg. When BMS-189453 was administered to male rats at daily doses ranging from 12.5 to 100 mg/kg for 1 week, only minimal testicular changes occurred at all doses, shortly after the dosing period. However, after a 1-month drug-free observation period, marked testicular atrophy was evident at all doses. BMS-189453 was then administered at doses of 2, 10, or 50 mg/kg to male rats for 1, 3, or 7 consecutive days. Dose- and duration-dependent testicular toxicity that occurred after a 1-month observation period did not recover, and, in some cases, was more severe 4 months after the last dose. In rabbits administered BMS-189453 at oral doses of 2, 10, or 50 mg/kg for 1 week, testicular degeneration and atrophy were evident in the high-dose group at 1 month following treatment. These studies indicate that retinoid antagonists can selectively produce progressive and prolonged testicular toxicity after single or repeated oral doses that are otherwise well tolerated.
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PMID:BMS-189453, a novel retinoid receptor antagonist, is a potent testicular toxin. 1115 23

The possible involvement of oxidative damage in the progression of atherosclerosis has been suggested. There is some evidence that antioxidant therapy may be beneficial for the prevention of coronary heart disease. In this study, we investigated the relationship between coronary artery disease (CAD) and serum antioxidative status by measuring the total antioxidant status (TAS). Other relevant antioxidants, such as retinol, alpha, gamma-tocopherol, ascorbic acid, alpha, beta-carotenoids, erythrocyte glutathione peroxidase (GSH-Px) and oxidative products, were also determined in 31 male CAD patients with angiographically defined CAD and 66 male controls, aged 40-70 years, in a case-control study. The TAS levels, ratio and the concentrations of retinol, albumin, total protein and HDL cholesterol were significantly lower in the CAD patients than in the controls (p<0.01), and alpha-tocopherol and alpha/gamma-tocopherol were significantly higher in the CAD patients than in the controls. The TAS level correlated positively with gamma-GTP, GPT, GOT and uric acid (p<0.01). A multiple regression analysis in the CAD patients revealed that the TAS levels correlated most negatively with the number of diseased vessels. The concentrations of carotenoids and GSH-Px, as well as the alpha/gamma-tocopherol ratio were also significantly associated. Although conditional logistic regression analysis suggested low levels of HDL-cholesterol to be a significant coronary risk factor (OR=5.1, 95% CI=1.09-24.3), the TAS level showed no significant independent contribution to CAD. This study demonstrated an association of antioxidant parameters with the atherosclerosis progression, however, it did not confirm antioxidants as an independent risk factor for CAD event.
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PMID:Association of serum antioxidant capacity with coronary artery disease in middle-aged men. 1193 18

The European Commission Recommendation 2006/576/EC, suggests that the maximum level of Ochratoxin A (OTA) in poultry feeds should be set at 0.1 mg OTA/kg. Thirty-six one-day-old male Hubburd broiler chickens were divided into two groups, a Control (basal diet) and an Ochratoxin A (basal diet + 0.1 mg OTA/kg) group. The growth and slaughter performance traits were recorded. The liver, spleen, bursa of Fabricius and thymus weights were measured. The erythrocyte and leukocyte numbers were assayed in blood samples, and the heterophils to lymphocytes (H/L) ratio was determined. Alpha-1-acid glycoprotein (AGP), lysozyme, the total protein and the electrophoretic pattern were evaluated in serum samples. Liver enzymes (alanino aminotransferase, ALT and aspartate aminotransferase, AST) and kidney function parameters (uric acid and creatinine) were quantified. The results revealed that feeding a 0.1 mg OTA/kg contaminated diet to chicks caused a decrease in the absolute thymus weight (p < 0.05) and a lower total protein (p < 0.01), albumin (p < 0.01), alpha (p < 0.05), beta (p = 0.001) and gamma (p = 0.001) globulins serum concentration in the Ochratoxin A group. Moreover, the albumin-to-globulin (A/G) ratio of the OTA-treated animals resulted to be higher (p < 0.05). Feeding broiler chickens, a diet contaminated with the maximum level admitted by the European Commission Recommendation (0.1 mg OTA/kg), did not affect the animal performance, slaughter traits, organ weights, haematological parameters, liver enzyme or renal function parameters concentrations but had an overall immunosuppressant effect, with reduction in the thymus weight and of the total serum protein, albumin, alpha, beta and gamma globulins concentration.
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PMID:Feeding a diet contaminated with ochratoxin A for chickens at the maximum level recommended by the EU for poultry feeds (0.1 mg/kg). 1. Effects on growth and slaughter performance, haematological and serum traits. 2363 13

Based on a review of the literature, reference intervals for water buffalo (Bubalus bubalis) serum biochemistry and haematology have not previously been published. The current study was done to establish reference intervals for water buffalo heifers. The International Federation of Clinical Chemistry stated that at least 120 values are necessary to obtain reliable estimates for reference intervals. A total number of 127 clinically healthy buffalo heifers (1-2 years old) were included in the study. Animals were examined at buffalo farms that belong to Assiut Governorate, Egypt. Three types of samples were collected: serum samples for biochemical analysis, whole blood samples for haematological analysis and faecal samples for parasitological examination. Animals that fitted the inclusion criteria were included in the study. Biochemical analysis included serum total proteins, albumin, total globulins, alpha, beta and gamma globulin levels, and aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, creatine phosphokinase and lactate dehydrogenase activity. In addition to the above, serum creatinine, urea, total bilirubin, direct bilirubin, indirect bilirubin, sodium, potassium, chloride, magnesium, calcium, phosphorus, copper, zinc, iron, triglycerides, high density lipoprotein, low density lipoprotein, very low density lipoprotein, glucose levels and 20 haematological variables were measured. The 95.0% reference intervals were calculated by removing the upper and lower 2.5% of the interval for each serum biochemical constituent to give the 2.5 and 97.5 percentiles. Confidence intervals were calculated for each reference limit. Reference intervals from the current study were compared with established values for cows. The current study is as far as could be determined the first that establishes reference intervals for the serum biochemical and haematological parameters in water buffalo heifers.
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PMID:Serum biochemical and haematological reference intervals for water buffalo Bubalus bubalis heifers. 2483 56