Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous methods to deplete in vivo concentrations of reduced glutathione (GSH) have not been able to lower tissue GSH levels for extended periods, have been toxic, and can alter the metabolism of xenobiotics. A possible alternative to lower in vivo concentrations of GSH may be the use of buthionine-S,R-sulfoximine (BSO) in the drinking water of laboratory animals to inhibit the biosynthesis of GSH. It has been previously reported that 20 mM BSO in the drinking water given to mice was able to lower GSH levels in a variety of tissues after 15 days. In order to more fully characterize the in vivo depletion of GSH in tissues by ingestion of BSO and determine if this method would be suitable in studies requiring depressed levels of GSH for extended periods, we added different amounts of this agent to the drinking water given to mice for various times up to 28 days. We found that ingested BSO at the highest concentration used in drinking water (30 mM) was able to maximally lower GSH concentrations in mouse lungs, lung lavage fluid, liver, kidneys, and blood to 59.0 +/- 3.6%, 35.0 +/- 5.1%, 44.3 +/- 1.5%, 69.5 +/- 3.9%, and 70.0 +/- 6.0% of control mice, respectively, for up to 28 days. These lowered concentrations of tissue GSH returned to control levels after mice were returned to untreated drinking water for 7 days. The potential toxicity of such treatments was also evaluated. Levels of alkaline phosphatase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, glutathione peroxidase, and glutathione reductase in lungs and lung lavage fluid, and total and differential cell counts from lung lavage fluid were not different between control and BSO-treated mice. This showed that BSO treatment did not produce indications of lung injury as measured by these biochemical parameters. Serum aspartyl transferase and gamma-glutamyl transpeptidase activities were unaffected by the BSO treatments, indicating normal liver functions. Lung and liver cytochrome P-450 concentrations were also not different between controls and BSO-treated animals. Thus, BSO in the drinking water of mice was able to effectively lower in vivo levels of GSH without eliciting acute toxic responses.
 ...
PMID:Effects of the long-term depletion of reduced glutathione in mice administered L-buthionine-S,R-sulfoximine. 286 40

A monkey model has been set up for protein calorie malnutrition and calcium deficiency. Oral exposure of 5ppm Cd/kg body wt./day for 24 weeks led to increased excretion of Cd, metallothionein (MT) and zinc. Rehabilitation of PCM monkeys for one year resulted in gradual reduction and finally complete disappearance of urinary metallothionein. During Cd exposure, the accumulation of Cd and induction of MT was significantly higher in liver, kidney and intestine. MT was also induced in heart, lung and testis of Cd exposed PCM and calcium deficient monkeys. Metallothionein from liver has been resolved into three isoforms, viz MTa, MTb and MTc on DEAE-Sephadex A 25 ion exchange column. MTc is the major isoform in Cd-treated, normal and protein calorie malnourished monkeys whereas MTb is the major isoprotein in the cadmium treated calcium deficient monkeys. The iso-metallothioneins varied in their metal composition in the nutritional stress conditions and showed different capacities to reactivate apo-enzymes viz. alkaline phosphatase, ceruloplasmin, superoxide dismutase and glutathione peroxidase. Thus, metallothionein plays a key role in metal metabolism during cadmium toxicity under nutritional stress conditions.
 ...
PMID:Role of metallothionein in metal detoxification and metal tolerance in protein calorie malnutrition and calcium deficient monkeys (Macaca mulatta). 295 56

Selenium deficiency has been implicated as a cause of hepatic injury, possibly from accentuated lipoperoxidation due to decreased activity of the selenoenzyme, glutathione peroxidase. Because of possible clinical and biochemical links between selenium and alcohol, we performed nutritional assessment and assayed red blood cell, plasma, and whole blood selenium by spectrofluorometry in 27 normals (group I), 30 asymptomatic alcoholics on admission to a detoxification unit, (group II) and 16 alcoholics with severe liver disease (group III). We found a mean (+/- SD) whole blood selenium of 0.109 micrograms/ml +/- 0.014 for group I vs 0.076 +/- 0.010 for group II (P less than 0.001), and 0.047 +/- 0.006 for group III (P less than 0.001 vs group I and II). For plasma, the mean (+/- SD) selenium was 0.095 micrograms/ml +/- 0.016 for group I versus 0.065 micrograms/ml +/- 0.012 in group II and 0.038 micrograms/ml +/- 0.007 in group III (All P less than 0.001). Calculated red blood selenium levels were also significantly reduced in alcoholics versus controls. Whole blood and plasma selenium correlated directly with serum albumin. For whole blood selenium versus albumin, r = 0.73 (P less than 0.01), and for plasma selenium versus albumin, r = 0.71 (P less than 0.01). A significant inverse correlation was noted between whole blood selenium and the height of the total serum bilirubin (r = -0.46), alkaline phosphatase (r = -0.50), and AST (r = -0.51) (P less than 0.01 for all). Among alcoholics admitted for detoxification, selenium was diminished despite the absence of severe malnutrition, as determined by standard nutrition assessment parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Low blood selenium levels in alcoholics with and without advanced liver disease. Correlations with clinical and nutritional status. 402 13

Male BALB/c mice were treated with intraperitoneal injections of carbon tetrachloride (CCl4) (0.2 g/kg body weight) and/or 50 R of whole-body gamma irradiation, three times per week, for 4 weeks. The effects of the treatments on superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in liver extracts and homogenates, and on alkaline phosphatase (ALP) in serum were investigated. A significant decrease in the SOD and GSH-Px activities in liver extracts and an increase of serum ALP of hepatic origin were found in CCl4-treated animals. In contrast, only an increase in SOD activity was observed in liver homogenates after the combined treatment.
 ...
PMID:Interaction of low doses of ionizing radiation and carbon tetrachloride on liver superoxide dismutase and glutathione peroxidase in mice. 408 56

A number of plasma biochemical parameters were examined in five outbreaks of runting in broiler chickens. In four of the five outbreaks, runts showed consistent elevations in plasma amylase activity and reductions in glutathione peroxidase activity. In two of the five outbreaks the plasma vitamin E concentration was reduced, as was the activity of plasma alkaline phosphatase. A highly significant number of runted chickens were found to have pancreatic degeneration, elevated plasma amylase activity and reduced plasma glutathione peroxidase activity, compared with non-runted chickens. The implications of these changes are discussed in relation to the aetiology of runting and stunting syndrome and, in particular, the possible involvement of selenium.
 ...
PMID:Pancreatic degeneration in broilers with runting and stunting syndrome. 608 56

The pulmonary biochemical and morphological changes resulting from the inhalation of relatively low levels of NO2 for up to 15 wk were investigated. Specific pathogen-free Fischer 344 rats were exposed to 0, 1, or 5 ppm NO2 or 1 ppm with two spikes to 5 ppm NO2 for 7 h/d, 5 d/wk for up to 15 wk. These exposures produced a mild concentration-related pulmonary injury, with the 5-ppm group sustaining the most damage. The other NO2-exposed animals showed similar types of damage, although the extent was less than that observed in the 5-ppm-exposed group. After 15 wk of exposure, histopathological examination revealed focal areas of hyperinflation and alveolar macrophage accumulation in some of the 5-ppm- and 1-5-ppm-exposed-exposed animals. These changes were preceded by a series of biochemical changes in the bronchoalveolar lavage fluid. Cell necrosis was indicated by elevated lavage fluid concentrations of lactate dehydrogenase after 1.7 to 2.7 wk of exposure. Also elevated were alkaline phosphatase and glutathione peroxidase. Lung tissue levels of glutathione reductase and glucose-6-phosphate dehydrogenase were also increased, indicating a possible protective response to the oxidant gas. After 15 wk of exposure, all biochemical indicators of injury has resolved. These data suggest that intermittent exposure to relatively low levels of NO2 with spike concentrations produces biochemical changes that resolve with continued exposure but produce histopathological changes that may persist with continued exposure.
 ...
PMID:Pulmonary effects of intermittent subacute exposure to low-level nitrogen dioxide. 668 55

After application of SnCl2 and tin incorporated into baker's yeast, the effects on carbonic anhydrase (CA), glutathione peroxidase (GPx), lactate dehydrogenase (LDH), alkaline phosphatase (AP) and leucine aminopeptidase (LAP) were measured. The tin contents of liver and kidneys were determined. CA and GPx are not affected. AP and LAP are inhibited by high concentrations of tin (as SnCl2). Tin incorporated into yeast exerts no effect. Inorganic tin produces increases in liver and kidneys.
 ...
PMID:[Effects of tin on rats. II. Comparison of the effects of tin (II) chloride and yeast-incorporated tin]. 677 55

The biochemical and clinical effects of selenium (Na2SeO3) on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in male Sprague-Dawley rats are presented. A 4-ppm selenium supplement to the drinking water was provided before, during, and after 20 weekly injections of 20 mg DMH per kg body weight. Immediately after the 20th DMH injection, part of the rats were sacrificed. The incidences of colon tumors in groups provided selenium before DMH, before and during DMH, and only during DMH treatment were reduced to 39, 43, and 36%, respectively. The incidence in the DMH only control was 63%. Other rats in all treated and control groups were maintained up to 5 months post-DMH treatment. At 10-week intervals throughout the study, selected blood and tissue components were analyzed. The following hematological changes correlated with DMH treatment. (a) Serum glutamic oxalacetic transaminase increased 2-fold (normal, 66 +/- 14 g/dl). (b) Serum alkaline phosphatase increased 24% (normal, 166 +/- 56 units/liter). (c) Serum protein decreased 14% (normal, 6.77 +/- 0.48 g/dl). (d) White blood count increased 2- to 3-fold (normal, 7.7 +/- 2.7 X 10(3)/cu mm). And (e) hemoglobin decreased 67% (normal, 18.1 +/- 1.3 g/dl). The magnitude of these changes varies with each selenium treatment group and with each 10-week analysis period. Provision of 4 ppm selenium doubled both liver and blood selenium levels compared to unsupplemented controls. The effects of selenium and DMH treatments on glutathione peroxidase and beta-glucuronidase activities and on sialic acid are presented. Possible mechanisms by which selenium protects against DMH-induced neoplasia are discussed.
 ...
PMID:Biochemical and clinical effects of selenium on dimethylhydrazine-induced colon cancer in rats. 730 70

Acute and chronic effects of Se as sodium selenite given as a supplement in the drinking water of Sprague-Dawley rats for 35 d, 1 yr, and 2 yr are compared. For the 35-d study the experimental groups were untreated controls and rats supplemented with 1, 4, 8, 16, and 64 ppm Se. Survival was 100% in the control and 1 and 4 ppm groups, decreased in the 8 and 16 ppm groups, and was zero in the 64 ppm group. Body weights increased and were equivalent in the control and 1 and 4 ppm groups and substantially decreased in the 16 and 64 ppm groups., Serum alkaline phosphatase and glutamic-oxaloacetic transaminase (SGOT) increased with 16 ppm Se and higher supplements. Se toxicity was apparent in microscopic pathology showing liver congestion, fatty degeneration of parenchymal cells, and necrosis. In the chronic studies untreated controls are compared with rate receiving 4 ppm Se in the drinking water. In general, the weight gains throughout were equivalent for both groups. The 1-yr survival in each was above 90% and the 2-yr survival above 50%. With increased age there was a slight reduction in hemoglobin and white blood cells. The latter effect was greater in Se-treated then in control rats. Several serum components were equivalent in both groups, including alkaline and acid phosphatase, SGOT, protein, glucose, and sialic acid. Liver glutathione peroxidase was half and Se levels in the Se-treated rats were twice those in the controls. Data are presented for male rats in the chronic study with occasional reference to data on females. The parameters measured in the chronic study are highly dependent on the age of the rat when Se-supplemented drinking water is initiated.
 ...
PMID:Toxicological effects of sodium selenite in Sprague-Dawley rats. 733 30

Se as sodium selenite was administered by gavage (three consecutive times) and as drinking water supplements for 46 d to male and female Swiss mice. With respect to survival in 7-wk-old mice, Se was less toxic in males than in females when gavaged. Drinking water supplements of 1-64 ppm Se resulted in 1 male and 1 female death in mice first given Se at 7 wk of age. Se supplements to the drinking water of adult (18-wk-old) mice was less toxic in females. All young (7-wk-old) and adult (18-wk-old) mice provided 1-16 ppm Se in the drinking water survived the 46-d treatment, but in adult mice 64 ppm Se significantly reduced survival. Only 64 ppm Se supplements caused a sharp reduction in body weight in young and adult mice of both sexes. Supplements of 1-8 ppm Se in all mice elicited growth responses similar to those of untreated controls. Occasional liver and kidney congestion, liver necrosis, parenchymal cell degeneration, and bile duct proliferation were observed in control and treatment groups. Serum alkaline phosphatase and glutamic-oxaloacetic transaminase (SGOT) increased with 32 ppm Se and higher supplements. Survival, growth, serum enzymes, and pathology were normal in untreated controls and in mice of growth ages and sexes give 1, 4, and 8 ppm Se supplements. A chronic toxicity study was conducted in female Swiss mice given 1, 4, and 8 ppm Se supplements for 50 wk. The survival of Se-treated groups was more than 90% and that of controls was only 72% after 50 wk. All mice gained weight, but the group treated with 8 ppm Se gained half as much as other groups. Both liver Se and glutathione peroxidase activity increased in Se-treated mice compared to controls at 25 and 50 wk. A reduced white blood cell count and increased alkaline phosphatase and SGOT suggested a mild toxic effect of the 8 ppm Se supplement in the chronic study.
 ...
PMID:Toxicological effects of sodium selenite in Swiss mice. 733 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>