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

Mercury is a well-recognized health hazard and an environmental contaminant. Mercury modulates immune responses ranging from immune suppression to autoimmunity but the mechanisms responsible for these effects are still unclear. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm mercury in drinking water for 14 days. Body weight was reduced at the highest dose of mercury whereas the relative kidney and spleen weights were significantly increased. The dose range of mercury used did not cause hepatotoxicity as indicated by circulating alanine aminotransferase and aspartate aminotransferase levels. Circulating blood leukocytes were elevated in mice treated with the highest dose of mercury. Mercury ranging from 1.5 to 37.5 ppm dose-dependently decreased CD3(+) T lymphocytes in spleen; both CD4(+) and CD8(+) single-positive lymphocyte populations were decreased. Exposure to 7.5 and 37.5 ppm mercury decreased the CD8(+) T lymphocyte population in the thymus, whereas double-positive CD4(+)/CD8(+) and CD4(+) thymocytes were not altered. Mercury altered the expression of inflammatory cytokines (tumor necrosis factor alpha, interferon gamma, and interleukin-12), c-myc, and major histocompatibility complex II, in various organs. Results indicated that a decrease in T lymphocyte populations in immune organs and altered cytokine gene expression may contribute to the immunotoxic effects of inorganic mercury.
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PMID:Oral exposure to inorganic mercury alters T lymphocyte phenotypes and cytokine expression in BALB/c mice. 1292 68

As stress is linked to many diseases, research on an effective antistress agent (adaptogen) from plants has gained importance. We report the investigations on the adaptogenic property of a standardized extract of Bacopa monniera against acute (AS) and chronic stress (CS) models in rats. Panax root powder (Panax quinquefolium) was taken as a standard. Male SD rats, weighing 180-200 g, exposed to immobilization stress for 150 min once only for AS and for seven consecutive days in CS, were fed with B. monniera or Panax root powder daily for 3 days in AS and for 7 days in CS, 45 min prior to each exposure of stress. Rats were sacrificed immediately after stress, the blood was collected, and the plasma was separated out for biochemical estimation. Adrenals, spleen, and thymus were dissected for organ weight and stomach for ulcer score. AS exposure significantly increased the ulcer index, adrenal gland weight, plasma glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK) but significantly decreased the spleen weight. Pretreatment with B. monniera at 40 mg/kg po significantly reduced the AS-induced increase in the ulcer index, adrenal gland weight, plasma glucose, AST, and CK. A dose of 80 mg/kg po significantly reversed the AS-induced changes in adrenal gland weight, spleen weight, plasma glucose, ALT, and AST. Panax root powder, 100 mg/kg po, significantly reversed the AS-induced changes in spleen weight, plasma ALT, AST, and CK. CS exposure resulted in a significant increase in the ulcer index, adrenal gland weight, plasma AST, and CK with a significant decrease in the thymus and spleen weight, plasma triglyceride, and cholesterol. Pretreatment with low dose of B. monniera extract at 40 mg/kg significantly reversed changes in ulcer index and plasma AST only, whereas the pretreatment with higher dose significantly reversed CS-induced changes in ulcer index, adrenal gland weight, CK, and AST. Panax root powder significantly reversed CS-induced increase in ulcer index, adrenal gland weight, CK, and AST. On the basis of our result, it is concluded that the standardized extract of B. monniera possesses a potent adaptogenic activity.
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PMID:Adaptogenic effect of Bacopa monniera (Brahmi). 1295 24

In the present studies, the acute toxic effects of 2-bromopropane (2-BP) and its analog, 1,2-dibromopropane (1,2-DBP), were investigated in female BALB/c mice. The mice were treated orally with either 2-BP at 2000 and 4000 mg/kg or 1,2-DBP at 300 and 600 mg/kg. Four days before necropsy, the mice were immunized intraperitoneally with sheep red blood cells (SRBCs). 1,2-DBP reduced the weights of the spleen and thymus weights and decreased the number of splenic cells. In addition, treatment with 1,2-DBP suppressed the antibody response to SRBCs. Meanwhile, only the antibody response was significantly suppressed by treatment with 2-BP. In the subsequent studies, the time course effects of 2-BP and 1,2-DBP on the hepatotoxic parameters were compared in female BALB/c mice. When mice were treated orally with either one of these chemicals for 6, 12, 24 and 48 h, the activities of serum alanine aminotransferase and aspartate aminotransferase elevated significantly only with 1,2-DBP 24 h after the treatment. The hepatic content of glutathione was reduced by 1,2-DBP. Meanwhile, these parameters were increased by 2-BP. The present results suggest that 1,2-DBP in the Solvent 5200 also contributes to the immnunotoxicity, although 2-BP is a major component.
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PMID:Acute effects of 2-bromopropane and 1,2-dibromopropane on hepatotoxic and immunotoxic parameters in female BALB/c mice. 1466 61

Three experiments were conducted to assess mortality rate, blood chemistry, and histologic changes associated with acute exposure to T-2 mycotoxin in adult bobwhite quail. In Experiment 1, adult quail were orally dosed with T-2 toxin to determine the lethal dose that resulted in 50% mortality of the affected population (LD50), and that dose was determined to be 14.7 mg of T-2 toxin per kilogram of body weight (BW). A second experiment was performed to study the effects of 12-18 mg/kg BW T-2 toxin on blood chemistry and liver enzyme profiles. Posttreatment uric acid, aspartate aminotransferase, lactic dehydrogenase, and gamma glutamyltransferase increased as compared with pretreatment values. In contrast, posttreatment plasma total protein, cholesterol, and triglyceride levels numerically decreased as compared with pretreatment values. Changes in blood chemistry values were consistent with liver and kidney damage after T-2 toxin exposure. In Experiment 3, histologic analyses of bone marrow, spleen, liver, small intestine, kidney, and heart were conducted on birds dosed in Experiment 2. Marked lymphocyte necrosis and depletion throughout the spleen, thymus, bursa, and gut-associated lymphoid tissue in the small intestine were observed in birds dosed with 15 and 18 mg/kg BW T-2 toxin. Necrosis of liver and lipid accumulation as a result of malfunctioning hepatocytes were also observed. Little or no morphologic change was observed in bone marrow and heart tissue. The LD50 for adult bobwhite quail as found in this study is two to three times higher than that reported for other species of commercial poultry. Results from these data confirm previous reports of immunosuppressive and/or cytotoxic effects of T-2 toxin in other mammalian and avian species. T-2 toxin may have a negative impact on the viability of wild quail populations.
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PMID:Determination of the acute 50% lethal dose T-2 toxin in adult bobwhite quail: additional studies on the effect of T-2 mycotoxin on blood chemistry and the morphology of internal organs. 1528 27

Indices of oxidative stress, nitric oxide (NO) metabolism as well as the activity of caspase-3, an important enzyme of apoptotic cell death, were measured during the morphine withdrawal syndrome in liver and thymus of rats. Male Wistar rats were administered with morphine hydrochloride (i.p., at increasing doses from 10 to 100 mg/kg, twice a day, for 6 days). Thirty-six hours after the last administration the withdrawal syndrome was monitored using the specific autonomic and locomotor indices. During this period, weights of body and thymus significantly decreased. Oxidative stress in liver was accompanied by an increase in aspartate aminotransferase and gamma-glutamyl transferase in blood serum. No signs of oxidative stress could be demonstrated in thymus. The activity of the Ca(2+)-dependent isoform of nitric oxide synthase (NOS) in liver increased, while, the activity of the Ca(2+)-independent NOS diminished, the total activity of NOS in liver and thymus remained unchanged. The concentration of nitrates/nitrites in blood was decreased, in thymus increased, and in liver unchanged. Caspase-3 activity changed neither in liver, nor in thymus. The results are discussed from the perspective of possible antioxidant and antiapoptotic role of NO during morphine withdrawal syndrome.
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PMID:[Effects of morphine withdrawal on the indices of free radical homeostasis and nitric oxide system in rat liver and thymus]. 1562 95

Methanol is primarily metabolized by oxidation to formaldehyde and then to formate. These processes are accompanied by formation of superoxide anion and hydrogen peroxide. This paper reports data on the effect of methanol on antioxidant status and lipid peroxidation in lymphoid organs such as the spleen, thymus, lymph nodes and bone marrow of rats. Male Wistar albino rats were intoxicated with methanol (2.37 g/kg b.w intraperitoneally) for detecting toxicity levels for one day, 15 d and 30 d, respectively. Administration of methanol at 15 and 30 d significantly (p<0.05) increased lipid peroxidation and decreased the enzymatic (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic antioxidants (reduced glutathione and vitamin C) in lymphoid organs. However, lipid peroxidation and enzymatic and non-enzymatic antioxidants in the acute methanol exposed group animals were found to be significantly (p<0.05) increased. In one day methanol intoxication, the levels of free radicals initially increased, and to remove these free radicals, antioxidants levels were elevated, which generally prevented oxidative cell damage. But in longer periods of intoxication, when the generation of reactive free radicals overwhelmed the antioxidant defense, lipid peroxidation increased. Further, decreased antioxidants in 15 and 30 d methanol intoxication may have been due to overutilization of non-enzymatic and enzymatic antioxidants to scavenge the products of lipid peroxidation. In addition, the liver and kidney markers of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine significantly increased. This study concludes that exposure to methanol causes oxidative stress by altering the oxidant/antioxidant balance in lymphoid organs of the rat.
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PMID:Methanol-induced oxidative stress in rat lymphoid organs. 1648 59

This study was carried out to investigate the potential subchronic inhalation toxicity of dimethyl disulfide (DMDS) via whole-body exposure in F344 rats. Groups of 10 rats of each sex were exposed to DMDS vapor by whole-body exposure at concentrations of 0, 5, 25, or 125 ppm for 6 h/day, 5 days/wk for 13 wk. All the rats were sacrificed at the end of treatment period. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. At 25 ppm, a decrease in the body weight gain, food intake, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and blood urea nitrogen (BUN) was observed in the males, but not in the females. However, at 125 ppm, a decrease in the body weight gain, food intake, and thymus weight and an increase in the weights of adrenal glands were observed in both genders. Serum biochemical investigations revealed a decrease in the AST, ALT, BUN, creatine phosphokinase (CPK), and triglyceride levels and an increase in the glucose level. In contrast, no treatment-related effects were observed in the 5 ppm group. The toxic potency of DMDS was slightly higher in males than that in females. In these experimental conditions, the target organ was not determined in rats. The no-observed-adverse-effect concentration (NOAEC) was found to be 5 ppm, 6 h/day for male rats and 25 ppm, 6 h/day for female rats.
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PMID:Evaluation of subchronic inhalation toxicity of dimethyl disulfide in rats. 1651 96

This study was designed to evaluate the hepatoprotective effects of S. miltiorrhiza polysaccharides (SMPS) in immunological liver injury induced by Bacille-Calmette-Guerin (BCG) and lipopolysaccharide (LPS) in mice. SMPS effectively improved the liver index, spleen index and thymus index, reduced the serum levels of alanine aminotransferase, aspartate aminotransferase and nitric oxide, and restored liver homogenate contents of tumor necrosis factor-alpha and interleukin-1beta. The histopathological analysis suggested that SMPS reduced the degree of liver injury. The results suggest that SMPS play a protective role against immunological liver injury, which may have important implications for our understanding on the immunoregulatory mechanisms of polysaccharides.
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PMID:Protection of a polysaccharide from Salvia miltiorrhiza, a Chinese medicinal herb, against immunological liver injury in mice. 1857 Dec 29

This study comprehensively describes the effects of various levels of food reduction on a wide range of toxicological parameters in dietary-optimized rats (fed with approximately 75% of ad libitum food consumption daily; 16 g and 22 g/day for females and males, respectively) that has been established as a nutritionally appropriate and well-controlled animal model in conducting toxicity studies. Toxicological parameters, including general condition, ophthalmology, clinical pathology and anatomic pathology, were examined in dietary-optimized Crl:CD(SD) female and male rats fed 16 g and 22 g/day (control), 12 g and 17 g/day (75% group), 8 g and 11 g/day (50% group), or 4 g and 6 g/day (25% group), respectively for 2 weeks. There was mortality and morbidity including reddish urine in 25% group females. The reddish urine was identified as "hemoglobinuria" that resulted from extra/intra-vascular hemolysis induced by severe food reduction. Hemoconcentration, decreased leukocytes and platelets, decreases in nutritional elements (serum glucose, protein, and lipids), increased aspartate aminotransferase and alanine aminotransferase, imbalanced electrolytes, and/or decreased urinary pH were observed in all restriction groups. Histopathologically remarkable changes included erythrophagocytosis in the spleen/liver and renal tubular necrosis with hyaline cast/droplets in 25% group; in addition to bone marrow depletion, lymphoid depletion in thymus/spleen/lymph node, and/or decreased secretion in the prostate/seminal vesicle in all restriction groups. Most of these changes were considered attributable to nutritional deficiency, dehydration, accelerated protein catabolism, stress and/or hemolysis secondary to severe food reduction. These results will enable toxicologists to help distinguish primary drug-induced effects from secondary changes associated with decreases in food consumption.
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PMID:Effects of reduced food intake on toxicity study parameters in rats. 1904 75

Anisomycin is a pyrrolidine antibiotic isolated from Streptomyces griseolus. Recent studies have shown that Anisomycin as a novel immunosuppressive agent is superior to Cyclosporine A (J. Immunother. 31, 858-870, 2008). In order to make toxicological evaluation of Anisomycin, acute and four-week continuously intravenous toxicity studies were performed in mice. IC(50) value tested on peripheral lymphocytes was 25.44 ng/ml. The calculated LD(50) for Anisomycin was 119.64 mg/kg. The mice were intravenously injected through mouse tail vein with a total dose of 5, 15, 30 and 60 mg/kg/mice of Anisomycin every other day for 4 weeks. Just in the high-dose mice, death of three mice happened and body weight of the mice was significantly decreased. Statistically significant changes in organ index included increases in ratios of the spleen, liver, lung and brain to the body weight, and decrease in ratio of the thymus to the body weight. Changes in clinical biochemistry parameters included increases in the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, and decreases in the glucose (GLU) activity. The distinct inflammation appeared in the lung, liver and kidney, and the number and size of megakaryocytes in the spleen were significantly increased. Anisomycin did not induce formation of the peripheral blood micronucleus, but increased the number of micronucleated polychromatic erythrocytes in bone marrow and sperm aberrations. However, the above aberrant changes occurred only in the mice treated with the high-dose Anisomycin. These results indicate that although Anisomycin has no significant side effects at effectively therapeutic doses, its over-dosage may lead to toxicity, particularly pulmo-, nephro- and hepato-toxicity.
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PMID:In vivo toxicological evaluation of Anisomycin. 2200 51


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