Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of aspartate aminotransferase (GOT), alanine aminotransferase (GPT), alkaline phosphatase (alkP), creatine kinase (CPK), and ornithine carbamoyltransferase (OCT) were determined in liver, heart, skeletal muscle, brain, kidney, lung, spleen, adrenals, pancreas, thyroid, thymus, and red cells of 56 bovine fetuses varying in gestational age from 115 to 255 days. The tissue aminotransferase activities were the most variable with gestational age. The GPT activity of liver, kidney, spleen, and red cells and the GOT activity of red cells decreased with fetal age. The GPT activity of heart, brain, and skeletal muscle and the GOT activity of adrenal, brain, and skeletal muscle increased with fetal age. Increasing activities were also described for adrenal and brain alkP and for brain and skeletal muscle CPK. In contrast, the OCT activities were fairly constant for each tissue as a function of gestational age.
 ...
PMID:Developmental changes of tissue enzyme patterns in the bovine fetus with gestational age. 116 76

Oral bropirimine (an immunomodulator shown to induce interferon) was administered to timed-pregnant Sprague-Dawley rats in five experiments utilizing several different dosing schedules. Concentrations of 100, 200, and 400 mg/kg of bropirimine were used. Interferon levels were determined in maternal serum, spleen, and whole embryo extracts and uterine contents were evaluated for survival of the embryos. Maternal toxicity occurred in all experiments as evidenced by dose-related decreases in body weight during the first 24 hr postdosing. Hematoxicology analyses of maternal serum revealed significant decreases in urea nitrogen, potassium, and albumin, along with increases in aspartate transaminase, alanine transaminase, and total bilirubin, in bropirimine-treated dams as compared to the vehicle controls. In addition, the means for maternal thymus weight decreased while the means for spleen weight increased with increasing concentration of bropirimine. As compared to the vehicle controls, interferon titers were high in maternal serum, maternal spleen, and, to a lesser extent, whole embryos, 2 hr postdosing, but had decreased or were below detectable levels 24 hr postdosing. Embryolethality was pronounced (increases in pre- and postimplantational loss) after a single dose (Gestation Day 3, 4, 5, 8, 9, or 10) of bropirimine, as well as after 7 or 8 consecutive days (Gestation Days 6-12 or 6-13) of treatment. Although embryotoxicity never occurred in these experiments in the absence of pronounced maternal toxicity, the pregnant dams never died as the result of bropirimine treatment, whereas the embryos frequently failed to survive.
 ...
PMID:Bropirimine-induced embryolethality after oral administration to the pregnant rat. 247 83

In order to assess the systemic toxicity of Zwittergent 3-14, a detergent used in the protein-detergent complex vaccines for its attractive immunogenic properties, a subacute toxicity study was performed. In this 4-week toxicity experiment five female and five male rats per group were injected intramuscularly with 0.25 ml of 0, 75, 750 and 7500 micrograms Zwittergent ml-1 sterile saline solution. Body weight and food intake were recorded weekly. At day 24 urine was collected for semiquantitative (pH, protein, ketone bodies, bilirubin and occult blood) and quantitative analyses (protein, creatinine and volume). At the end of the experiment blood was sampled for haematological [haemoglobin (Hb), packed cell volume (PCV), erythrocytes, leucocytes, reticulocytes and thrombocytes and differential white blood cell count] and biochemical analyses (alanine aminotransferase and aspartate aminotransferase. At necropsy brain, heart, liver, kidneys, spleen, thymus, adrenal glands, thyroid, pituitary gland, uterus, ovaries and testes were weighed. The underlined organs and the musculus quadriceps including the injection sites were examined histopathologically. Indications for systemic toxicity were noticed in the high-dose group and included occult blood in urine, elevated protein/creatinine ratio concomitantly with an increased urine volume and increased relative kidney weight indicating a slight disturbance of the kidney function. Some changes in haematological parameters (decreased PCV and increased numbers of thrombocytes eosinophils and monocytes) and a decreased glycogen content in the liver were recorded in the high dose group. These changes may be secondary to the extensive inflammatory reaction observed in the muscle of this high-dose group.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Subacute toxicity of Zwittergent administered intramuscularly. 281 72

Polychlorinated dibenzofurans are ubiquitous environmental pollutants which have great potential for human exposure. To characterize the toxicity of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF), male F344 rats were administered a single oral dose of 0, 100, 250, 500, 1000, or 2000 micrograms 4PeCDF/kg. A progressive and dose-dependent loss of body weight was evident by 3 days after treatment. Signs of toxicity included piloerection, hair loss, hypoactivity, morbidity, and death. Death occurred as soon as 14 days after treatment and continued throughout the 35-day observation period. The LD50/35 was estimated to be 916 micrograms/kg with a 95% confidence interval of 565-1484 micrograms/kg. Dose-dependent increases were observed in serum cholesterol, triglyceride, and bile acid concentrations and in sorbitol dehydrogenase and aspartate aminotransferase activities. The hematocrit, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin concentrations were depressed in a dose-dependent fashion. Hepatic ethoxyresorufin-O-deethylase (EROD) activity was increased in all treatment groups approximately 25 times above that of control animals. Lymphoid depletion in the thymus and spleen was observed in the three highest doses and thymic atrophy was present at all dose levels. Absolute liver weight and the liver:body weight ratio were significantly increased above controls. Hepatotoxicity was dose-dependent and was characterized by lipid accumulation resulting in hepatocytomegaly. Epithelial hyperplasia and focal ulcerations of the forestomach was observed in animals administered 500 micrograms 4PeCDF/kg. Spontaneous cardiomyopathy was exacerbated by treatment with 2000 micrograms/kg. Since 4PeCDF and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produce a similar spectrum of toxic effects, the biochemical mechanism(s) of toxicity for these chemicals may be similar.
 ...
PMID:The acute toxicity of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF) in the male Fischer rat. 322 Feb 3

The progression of aflatoxicosis was evaluated in growing crossbred barrows given 0, 1, 2, 3, or 4 mg of aflatoxin (AF)/kg of feed for 28 days (6 to 10 weeks of age). On day 28, pigs were euthanatized and necropsied, and tissues were removed for histologic examination. Body weight gains were decreased in barrows fed 2 mg of AF/kg after 7 days and in barrows fed 1 mg of AF/Kg after 14 days. By 28 days, all barrows fed AF had decreased body weights and weight gains. Compared with decreased in all barrows fed AF. Neither liver weights nor bone ash values were altered, although liver lipid values were increased in barrows fed AF. Serum aspartate transaminase, gamma-glutamyl transferase, and alkaline phosphatase activities were increased in barrows fed AF, whereas creatine kinase activity was decreased. Aflatoxin diets resulted in decreases in serum concentrations of urea nitrogen, phosphorus, cholesterol, albumin, and total protein. Histologic alterations in liver included interlobular fibrosis, periportal lipidosis, bile duct hyperplasia, and periportal lymphocytic infiltration. Lymphocytes in the thymus were depleted, and numbers of granulocytic cells in the bone marrow were reduced. The frequency and severity of lesions increased with increased doses of AF.
 ...
PMID:Progression of aflatoxicosis in growing barrows. 337 6

Clarified slurry oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 male and 10 female Sprague-Dawley rats 5 days/week for 13 weeks at doses of 8, 30, 125, or 500 mg/kg/day, and to another group for 2 weeks at doses of 2000 mg/kg/day. The rats were fitted with cardboard Elizabethan collars to minimize the ingestion of the test material, which was applied undiluted and remained uncovered on the skin. A similar group of rats served as controls; they were treated in the same manner except that no CSO was applied to their skin. There was a dose-related mortality and depression of body weight gain in the rats treated with CSO at doses of 30 mg/kg/day or greater; none of the rats dosed at 2000 mg/kg/day survived more than 2 weeks. The primary target organs of CSO toxicity were the liver, thymus, and bone marrow. The effects on the liver included increased weight (250% at 500 mg/kg/day), cholangiolitis, diffuse liver cell degeneration and hypertrophy, necrosis, fibrosis, decreased serum glucose, increased levels of alkaline phosphatase, aspartate aminotransferase, alanine amino transferase, bilirubin, and triglycerides. The thymus was found to be small and upon microscopic examination to be atrophic or hypoplastic. Erythroid hypoplasia was found in the bone marrow of some of the rats dosed at 30 mg/kg/day and increased in severity with increasing dose. The erythroid hypoplasia was accompanied by a dose-related anemia. Even in the rats dosed at 8 mg/kg/day, very slight abnormalities in the bile ducts were observed upon microscopic examination of the liver. Chromatographic separation and analyses demonstrated that CSO contains about 58% 3- to 5-ring polycyclic aromatic hydrocarbons (PAHs) and approximately 8-10% carbazole derivatives. In vitro and in vivo skin penetration studies demonstrated that the carbazole materials penetrate through the skin to a considerable extent (about 44%); less penetration was observed with 2- or 3-ring (8-13%) or 5-ring PAHs (3%).
 ...
PMID:Systemic toxicity from subchronic dermal exposure, chemical characterization, and dermal penetration of catalytically cracked clarified slurry oil. 359 Jan 98

Female BALB/c and B6C3F1 mice were examined after a 3-wk exposure to dietary estradiol (0, 400, 800, 1600, and 3200 ppb) in a purified (AIN-76A) or a natural-ingredient (NIH-07) diet. The use of AIN-76A was associated with a 9-13% greater (p less than 0.001) body weight and a 36-43% higher (p less than 0.001) serum cholesterol in both mouse genotypes when compared to mice fed NIH-07. Conversely, when fed NIH-07, both mouse genotypes had a 20-22% higher (p less than 0.003) serum urea nitogren and 2-3.5% higher erythrocyte count (p less than 0.001) and hemoglobin concentration (p less than 0.04) than when fed AIN-76A. Reduced erythrocyte parameters suggest that chronic feeding of the purified diet might result in anemia. No significant compound or diet-related differences were noted for serum creatinine, alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyl transferase. Although there was no diet effect on absolute or differential white blood cell count, estradiol caused a decrease in the total white blood cell count (p less than 0.014) and an increase in the percentage of polymorphonuclear leukocytes (p less than 0.014) in BALB/c and decreased the percentage of lymphocytes (p less than 0.005) in B6C3F1 females. In addition, estradiol increased uterine weight and inhibited thymic and splenic weights in one or both genotypes. Spleen and thymus weight responses to estradiol were not significantly influenced by diet. However, the uterine weight responses to estradiol were apparently influenced by diet in both genotypes. In B6C3F1 mice, the uterus weighed more at each level of estradiol when mice were fed AIN-76A compared to NIH-07 diet. In BALB/c mice, this was true only at the two lower dietary concentrations of estradiol. In conclusion, mice fed the purified diet, AIN-76A, differed from those fed the cereal-based diet, NIH-07, in hematology, clinical chemistry, and uterine weight response to estradiol.
 ...
PMID:Effects of purified (AIN-76A) and natural-ingredient (NIH-07) diets on responses of BALB/c and B6C3F1 female mice to estradiol. 368 22

The acute intravenous, intragastric, subcutaneous, intraperitoneal and intratracheal toxicity of T2 toxin has been studied in rats, mice, guinea-pigs, and pigeons. The acute LD50 values obtained varied between 1.0 and 14 mg X kg-1, there being little difference between the various routes in any given species. T2 caused vomiting in pigeons at doses of one fifth or less the LD50. In rats doses of 3.0 and 5.0 mg X kg-1 T2 produced lymphopenia, reticulocytosis, and in the highest dose groups normoblastaemia. Additionally, changes in plasma alkaline phosphatase and aspartate aminotransferase activities were seen. Histological changes were observed in lymphoid organs and were most severe in the thymus, lymph nodes, and Peyer's patches. The spleen was less severely affected. Gastrointestinal changes consisting of dead and dying lymphoid cells throughout the lamina propria were seen together with, in some cases, mucosal ulceration. The time course of the development and of the reversal of the changes was followed.
 ...
PMID:Acute toxicity of T2 toxin in rats, mice, guinea pigs, and pigeons. 381 Jun 51

Involution of the thymus was observed in rats bearing AH 130 (solid-type) tumors. The thymus weight decreased with tumor growth. Daily injection of a pharmacological dose of hydrocortisone into normal rats resulted in involution of the thymus and marked increase in alanine aminotransferase activity. This treatment also caused slight increase in the activity of tyrosine aminotransferase but not of aspartate aminotransferase in these animals. Involution of the thymus in tumor-bearing rats, however, was not accompanied by appreciable increases in the activities of these aminotransferases, even at an advanced stage of tumor growth when the plasma corticosterone level was very high and significant increase in the activities of all these enzymes was observed in the liver. Further, additional injections of hydrocortisone into rats with tumors weighing more than 5% of the body weight did not cause any appreciable change in alanine aminotransferase activity in the thymus, although in rats with smaller tumors it slightly increased the enzyme activity in the thymus. Furthermore, in normal rats, increase in alanine aminotransferase activity in the thymus with involution of the glands was observed with a dose of corticosterone close to the physiological range attained in rats with tumors in an advanced stage.
 ...
PMID:Aminotransferase activities and involution of the thymus in rats bearing AH 130 tumors. 611 Apr 78

Female Sprague-Dawley rats were fed diets containing 0, 0.01, 0.1, or 1.0 mg/kg 3,3',4,4',5,5'-hexabromobiphenyl (345-HBB) for 140 days after a 70% partial hepatectomy and diethylnitrosamine administration (10 mg/kg body weight) to determine if 345-HBB had tumor-promoting ability in a two-stage hepatocarcinogenesis assay. Tumor-promoting ability was assessed by measuring enzyme-altered foci exhibiting gamma-glutamyl transpeptidase activity. Enhancement of enzyme-altered foci occurred only at a dietary concentration of 345-HBB (1.0 mg/kg) that was toxic. The toxic effects were decreased body weight gain, involution of the thymus, increased liver weight, histologic and ultrastructural alterations of the liver, and elevated serum concentrations of aspartate aminotransferase. 345-HBB is a strict 3-methylcholanthrene (MC) type of hepatic microsomal drug metabolizing enzyme inducer and caused a dose-related increase of cytochrome P-450. 345-HBB, at a dietary concentration of 0.1 mg/kg, caused a physiologic response in rats as determined by induction of hepatic microsomal drug metabolizing enzymes, but there was minimal evidence of toxicity and no evidence of tumor-promoting ability. Results indicate that there can be induction of MC type of hepatic microsomal drug-metabolizing enzymes without toxicity or tumor-promoting ability and that the tumor-promoting ability of 345-HBB was most likely the result of hepatic degeneration and necrosis. This finding is in contrast to previous studies in which a closely related congener, 2,2',4,4',5,5'-hexabromobiphenyl, enhanced the development of enzyme-altered foci at dietary concentrations that were not hepatotoxic.
 ...
PMID:Hepatic tumor-promoting ability of 3,3',4,4',5,5'-hexabromobiphenyl: the interrelationship between toxicity, induction of hepatic microsomal drug metabolizing enzymes, and tumor-promoting ability. 631 5


1 2 3 4 5 6 Next >>