Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tocotrienols are added as antioxidants to food. As there have been no reports of toxicological evaluation, a 13-week oral toxicity study was performed in Fischer 344 rats of both sexes at dose levels of 0 (group 1), 0.19 (group 2), 0.75 (group 3) and 3% (group 4) of a preparation in powdered diet. Suppression of body weight gain was observed in group 4 males. On hematological examination, significant decrease in mean corpuscular volume (MCV) was observed in all treated males. Platelets were significantly reduced in group 3 and 4 males. Hemoglobin concentration, MCV, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were significantly decreased in group 3 and 4 females and hematocrit in group 4 females. On serum biochemical examination, increase in the albumin/globulin ratio (A/G) and alkaline phosphatase in all treated males, elevated alanine transaminase in group 4 of both sexes and increases in asparagine transaminase and gamma-glutamyl transaminase in group 4 females were observed. With regard to relative organ weights, liver weights in group 4 of both sexes and adrenal weights in all treated males demonstrated an increase, and ovary and uterus weights in group 4 females were reduced. Histopathologically, slight hepatocellular hypertrophy in group 3 and 4 males, and reduction of cytoplasmic vacuolation in the adrenal cortical region in group 4 males were observed. Because of pathological changes in male liver and hematological changes in females, the no-observed-adverse-effect level (NOAEL) was concluded to be 0.19% in the diet (120 mg/kg body weight/day for male rats and 130 mg/kg body weight/day for female rats). As a decrease in MCV, an increase in the A/G, elevation of alkaline phosphatase and increase in adrenal weight were observed in all treated males, a no-observed-effect level (NOEL) could not be determined in this examination.
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PMID:Oral toxicity of a tocotrienol preparation in rats. 1143 87

The purpose of this study was to determine ameliorative effects of crude aqueous extract of Anoectochilus formosanus (AFE) on osteopenia in ovariectomized (OVX) rats. First, all of the rats were divided into sham and OVX groups. The OVX rats were allowed to lose bone for 6 weeks. At 6 weeks post-OVX, the OVX rats were divided into four groups treated with water, 17beta-estradiol (30 microg/kg, daily s.c. injection) or AFE (0.5, 2 g/kg, daily, orally) for 12 weeks. In OVX rats, the increases of body weight and serum total cholesterol were significantly decreased by AFE or 17beta-estradiol treatment. In OVX rats, atrophy of uterus and vagina was preserved by treatment with 17beta-estradiol, but not by AFE. The decreased weight of pituitary was increased by treatment with both 17beta-estradiol and AFE. There were decreases in bone density and calcium content including the right femur and the fourth lumbar vertebra, when compared with the sham control rats. Treatment with either 17beta-estradiol or AFE ameliorated these changes induced by OVX. In addition, ovariectomy increased serum alkaline phosphatase levels. The increases were suppressed by the treatment with 17beta-estradiol and AFE. Our results demonstrated that AEF could ameliorate ovariectomy-induced osteopenia.
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PMID:Ameliorative effects of Anoectochilus formosanus extract on osteopenia in ovariectomized rats. 1153 69

Among the 10 commonly used therapeutic agents investigated, concurrent oral administration of tetracycline (140 mg/kg) twice daily on Days 1-5 post-coitum (pc) interfered with the post-coital anti-implantation activity and almost completely abolished estrogen antagonistic activity of the single anti-implantation (1.5 mg/kg, orally) dose of dl-ormeloxifene administered on Day 1 pc, resulting in the occurrence of resorbed implantations in 50% of the females. However, no such interaction was evident when tetracycline was administered intramuscularly or when ormeloxifene was administered at twice its anti-implantation dose. There was no effect of ormeloxifene and/or tetracycline treatment on serum estradiol and progesterone levels, and all animals presented apparently normal corpora lutea. Ormeloxifene administered per se inhibited aminopyrine-N-demethylase (AD), glucose-6-phosphate dehydrogenase (G-6-PDH) and glutathione-S-transferase (GST) in the liver on the day of maximal endometrial receptivity, which was prevented by tetracycline co-administration. Aniline hydroxylase and AD were not detected in small intestine or uterus in vehicle control or any of the treatment groups. There was, however, no effect of ormeloxifene plus tetracycline treatment on serum total alkaline phosphatase activity. Findings suggest that interference with anti-implantation action of ormeloxifene by tetracycline might be due primarily to the almost complete abolition of its estrogen antagonistic activity at the uterine level, effected by decreased bioavailability of ormeloxifene and/or its active metabolite(s) by altered enterohepatic recirculation because of the effect on gut microflora. This might alternatively be related to an increased rate of its metabolism and elimination from the system via prevention of ormeloxifene-induced inhibition of hepatic AD, G-6-PDH, and GST, which, by effecting a decreased rate of metabolism, might be responsible for prolonged (approximately 120 h) duration of estrogen antagonistic/anti-implantation action of ormeloxifene in this species.
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PMID:Interaction with anti-implantation and estrogen antagonistic activities of dl-ormeloxifene, a selective estrogen receptor modulator, by tetracycline in female Sprague-Dawley rats. 1174 77

Groups of five male and female Wistar rats were treated by gavage with 0, 0.01, 0.05 or 0.2 mg/kg body weight of the known synthetic estrogen ethinylestradiol for 28-32 days according to a modified enhanced OECD Test Guideline no. 407 in order to investigate which of the current and/or additional parameters would detect effects on the endocrine system reliably and sensitively and to provide data on intra-laboratory variability. Two identical studies (A and B) were run concurrently. The modified enhanced protocol requests the additional determination of triiodothyronine, thyroxine and thyroid-stimulating hormone (TSH), of the stage of the estrous cycle to ensure necropsy of all females in diestrus, of the number and morphology of cauda epididymal spermatozoa, and of additional organ weights (ovaries, uterus, thyroid, and male accessory reproductive organs), and histopathology of additional organs (pituitary, epididymides, coagulation glands, pancreas, and vagina). There were no treatment-related mortalities, clinical signs or changes in behavioral parameters. In male rats, 0.2 mg/kg was the maximum tolerated dose (MTD) resulting in reduced body weight gain. The only treatment-related alteration in hematological parameter was prolonged blood clotting time in high-dose females of both studies. Changes in clinical chemistry observed in study A were elevated alkaline phosphatase activity (high-dose females) and triglyceride levels (mid- and high-dose females and high-dose males). Changes in thyroid hormones and TSH of treated animals showed high variability with no clear dose-dependency, and could not be clearly related to estrogenic activity. In accordance to a suppression of the hypothalamic-pituitary-gonadal axis, decreased relative organ weights of the male accessory reproductive organs were obtained in both studies at the high dose. Corresponding histological changes were degeneration of the testicular germinal epithelium and atrophy of Leydig cells and of all accessory sex glands. Atrophy of the coagulating gland (study A) and seminal vesicles (study B) was also seen at 0.05 mg/kg. A marked increase in relative adrenal weight in male rats, accompanied by decreased vacuolization of zona fasciculata cells observed in both studies at the high dose seems to reflect an activation of the hypothalamic-pituitary-adrenal axis. The male mammary gland was sensitively affected. Increased numbers of small basophilic over large acidophilic cells indicated an estrogen-mediated feminisation and were detected at the low (study A) or mid dose (study B). Co-mitogenic properties of estrogens in rat liver were reflected by increased relative liver weights in females at the mid and high dose of study A and also at the high dose in study B. No treatment-related changes in endocrine organ weights were observed in treated females. Histological changes in the ovaries were increased numbers of apoptotic corpora lutea (from mid dose, study B) and of early stage follicles at the high dose in both studies. Classical direct estrogenic effects on the uterus, i.e. an increased height of luminal and glandular epithelium and increased granulocytic infiltration of the endometrium, were observed even at the low dose in both studies. Uterine findings occurring with a greater variability were dilation, squamous metaplasia of glands and thickened walls. Although females were necropsied in diestrus, as diagnosed by vaginal cytology, typical signs of estrogenic action in the vagina such as keratinization (indicative of estrus in normally cycling rats), mucification (indicative of proestrus), or thickened epithelia were observed in both studies even at the lowest dose. This unexpected discrepancy between vaginal cytology and vaginal and uterine morphology of treated females was considered to be treatment-related as it was not observed in the controls. Studies on liver enzymes that were performed outside the scope of the enhanced protocol showed that ethinylestradiol at 0.2 mg/kg decreased the activity of the sex-specific testosterone-dependent liver enzyme CYP2C11 in male rats. A simulation of doubling group size (to ten animals) by combining both studies did not increase the sensitivity of detection of endocrine-mediated effects above the level already obtained by histopathological examination of groups containing five animals. Only some of the enhancements to the current OECD Test Guideline no. 407 evaluated in this study (additional organs weights and additional histopathological investigations) were helpful in detecting the endocrine-mediated effects of ethinylestradiol, while other enhancements did not contribute towards this aim. Spermatology was completely insensitive at the MTD and measurement of thyroid hormones and TSH did not contribute to increased sensitivity. Vaginal cytology appeared to be an unreliable procedure for estrous cycle staging in estrogen-treated animals. Ongoing investigations, according to the modified version of the enhanced OECD Test Guideline no. 407 protocol, into the interference of ten compounds with the endocrine system by different mechanisms will result in the identification of the most appropriate enhancements.
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PMID:Sensitive detection of the endocrine effects of the estrogen analogue ethinylestradiol using a modified enhanced subacute rat study protocol (OECD Test Guideline no. 407). 1202 82

The efficacy of Tiron (4,5-dihydroxybenzene 1,3-disulfonic acid disodium salt) was examined in the treatment of beryllium-induced maternal and developmental toxicity in rats. Single administration of beryllium nitrate at a dose of 50 mg/kg (i.m.) on day 13 of gestation caused reductions in fetal and placental weights, the number of implantation sites and number of corpora lutea, as well as causing post-implantation loss, stunted growth, increase in the number of resorptions, and also a disturbed sex ratio. Maternal toxicity was demonstrated by reduction in body weight gain. Administration of beryllium also showed significant alteration in the hematological and biochemical indices of the mother as well as the fetus. Marked decreases were recorded in hemoglobin percentage, blood sugar levels, serum protein contents and serum alkaline phosphatase activity. By contrast, significant elevation was found in the activity of transaminases (aspartate aminotransferase and alanine aminotransferase). Tissue protein contents, glycogen contents, activities of alkaline phosphatase, adenosine triphosphatase and succinic dehydrogenase of kidney, lungs and uterus, and maternal and fetal liver all showed significantly decreased values after beryllium exposure, and remarkable elevation was observed in acid phosphatase, glucose-6-phosphatase and hepatic lipid peroxidation. These parameters were restored considerably with administration of 471 mg/kg i.m. Tiron from days 14 to 18 of gestation. Atomic absorption spectrophotometry also revealed a high concentration of beryllium in different organs of pregnant rats. Interestingly, a small amount of metal ion was also detected in the fetus and reduced accumulation of beryllium was noticed after Tiron treatment.
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PMID:Protective effect of Tiron (4,5-dihydroxybenzene-1,3-disulfonic acid disodium salt) against beryllium-induced maternal and fetal toxicity in rats. 1218 11

We evaluated whether hysterectomy with ovarian conservation (HYX) has an effect on bone metabolism and density in 176 healthy Caucasian postmenopausal women aged 48-59 years. Bone properties of the hip, spine, radius, tibia, and calcaneus were measured using different bone assessment modalities. In addition, bone turnover was assessed using serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), and tartrate-resistant acid phosphatase (TRAP) 5b as biomarkers. Our results showed that women having HYX had a significantly lower level of OC ( P = 0.017) and a marginally lower level of TRAP 5b ( P = 0.051) and higher bone mineral density (BMD) of the femoral neck ( P = 0.037) and lumbar spine ( P= 0.001) than women with no history of HYX. In addition, the cortical BMD and bone strength index (I(polar)) of the tibia also showed higher values at different sections in women having HYX than women with no history of HYX ( P = 0.055 to P< 0.005). These results suggest that the uterus may have a role in regulating bone metabolism that has not been detected previously.
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PMID:Does hysterectomy with ovarian conservation affect bone metabolism and density? 1249 Oct 88

A hormonal servomechanism has been proposed to regulate differentiation and function of the endometrial glandular epithelium (GE) in the ovine uterus during pregnancy. This mechanism involves sequential actions of estrogen, progesterone, ovine interferon tau (IFNtau), placental lactogen (oPL), and placental growth hormone (oGH). The biological actions of oPL in vitro are mediated by homodimerization of the prolactin receptor (oPRLR) and heterodimerization of the oPRLR and oGH receptor. The objectives of the study were to determine the effects of intrauterine oPL, oGH, and their combination on endometrial histoarchitecture and gene expression and to localize and characterize binding sites for oPL in the ovine uterus in vivo using an in situ ligand binding assay. Intrauterine infusion of oPL and/or oGH following IFNtau into ovariectomized ewes treated with progesterone daily differentially affected endometrial gland number and expression of uterine milk proteins and osteopontin. However, neither hormone affected PRLR, insulin-like growth factor (IGF)-I, or IGF-II mRNA levels in the endometrium. A chimeric protein of placental secretory alkaline phosphatase (SEAP) and oPL was used to identify and characterize binding sites for oPL in frozen sections of interplacentomal endometrium from pregnant ewes. Specific binding of SEAP-oPL was detected in the endometrial GE on Days 30, 60, 90, and 120 of pregnancy. In Day 90 endometrium, SEAP-oPL binding to the endometrial GE was displaced completely by oPL and prolactin (oPRL) but only partially by oGH. Binding experiments using the extracellular domain of the oPRLR also showed that iodinated oPL binding sites could be competed for by oPRL and oPL but not by oGH. Collectively, results indicate that oPL binds to receptors in the endometrial glands and that oPRL is more effective than oGH in competing for these binding sites. Thus, effects of oPL on the endometrial glands may be mediated by receptors for oPRL and oGH.
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PMID:Ovine placental lactogen specifically binds to endometrial glands of the ovine uterus. 1260 25

The present study was conducted to evaluate the therapeutic effectiveness of chelating agents [glutathione, 2,3 dimercapto propane sulfonic acid (DMPS) and D-penicillamine (DPA)] in combination with antioxidant (sodium selenite) in beryllium induced toxicity in female rats. A bolus dose of 50mg/kg-beryllium nitrate was administered singly followed by chelation therapy with GSH, DMPS + Se and DPA + Se at various durations of 1,3 and 7 days respectively. Results revealed a significant fall in the glycogen content, whereas, a marginal fall in the protein was also observed. The enzymatic activity of alkaline phosphatase and adenosine triphosphatase was depleted; on the contrary, there was a significant rise in the acid phosphatase and glucose-6-phosphatase pattern. A rise in the hepatic lipid peroxidation activity is a direct indication of oxidative damage resulting in free radical generation. The distribution of the metal by atomic absorption spectrophotometry revealed an increased concentration of beryllium in liver and kidney, followed by lung and uterus. The relative ability of three chelating agents to act as antagonists, for acute beryllium poisoning, have been examined in liver, kidney, lungs and uterus. The appreciable change in the beryllium concentration in various organs is duration dependent during the entire period being highly significant at 7 days regimen. Biochemical and distribution studies reveal that DPA + Se was the most effective therapeutic agent followed by DMPS + Se and GSH.
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PMID:Role of chelating agents and antioxidants in beryllium induced toxicity. 1262 5

The subchronic treatment of mature female Wistar-strain albino rats in diestrous phase with sodium arsenite at a dose of 0.4 ppm/100 g body weight/rat/day via drinking water for period of 28 days (seven estrous cycles) caused a significant reduction in the plasma levels of leutinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol along with a significant decrease in ovarian activities of delta five, 3 beta-hydroxysteroid dehydrogenase (Delta5,3beta-HSD), and 17 beta-hydroxysteroid dehydrogenase (17beta-HSD) followed by a reduction in ovarian and uterine peroxidase activities. A significant weight loss of the ovary and uterus was also observed after this treatment, along with a prolonged diestrous phase and a high accumulation of arsenic in the plasma and these organs. Moreover, sodium arsenite was also responsible for ovarian follicular and uterine cell degeneration characterized by a high number of regressing follicles and a reduction in the uterine luminal diameter, respectively, in comparison with the controls. A dietary supplementation of sodium selenite at the dose of 0.6 mg/100 g body weight/rat/day for a period of 28 days along with arsenic treatment minimized the gonadal weight loss significantly and increased the activities of the ovarian steroidogenic enzymes as well as the ovarian and uterine peroxidase at the control level. Selenium was also able to increase the plasma levels of LH, FSH, and estradiol toward the control level. Vaginal smears showed normal estrous cyclicity in sodium selenite-supplemented arsenic-treated rats along with lower arsenic levels in the plasma and gonadal tissue in comparison with arsenic-only-treated rats. Histological sections of ovary and uterine tissues in the control and experimental groups confirmed that sodium selenite supplementation was able to prevent arsenic-induced histopathological changes in the ovary and uterus. Plasma levels of norepinephrine and dopamine in the midbrain and diencephalon decreased significantly, whereas the serotonin level was increased significantly after 28 days of sodium arsenite treatment. All of these parameters were, in most cases, unchanged from the control level when sodium selenite was co-administered with sodium arsenite. Arsenic intoxication was also associated with increased liver weight and elevation in the activities of hepatic and renal acid phosphatase, alkaline phosphatase, and transaminases, but selenium co-administration was not able to change these toxic effects of arsenic. The results of our experiments indicate the significant protective action of sodium selenite on arsenic-induced toxicity in the female reproductive system, while there was no significant protective effect of selenium on arsenic-induced toxicity in other organs.
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PMID:Effect of dietary co-administration of sodium selenite on sodium arsenite-induced ovarian and uterine disorders in mature albino rats. 1288 85

Catechol-O-methyltransferase (COMT) enzyme is a widely distributed enzyme that catalyses O-methylation of catecholamines and other compounds having a catechol structure. Because there has been some concern about the consequences of a low COMT activity in the development of oestrogen-dependent cancers and because one of the COMT inhibitors, tolcapone, has caused serious liver injuries in Parkinsonian patients, the histopathology and clinical chemistry of Comt-gene-disrupted mice were studied at the age of 12 months. Owing to the high COMT activities in liver and kidney and the role of COMT in the metabolism of catechol oestrogens, special emphasis was given to the histology of the liver, kidney and oestrogen-dependent organs such as mammary glands and uterus. The mice of both heterozygous and homozygous genotypes appear to be physically healthy and fertile. Diurnal motility rhythm and behaviour in measuring anxiety and depression were equal in all genotypes. At the age of 12 months, the body weight of homozygous mice was 7-9% lower than that of the other groups. This was reflected in histology as a diminished incidence of vacuolation of liver cells (fatty change). Macroscopic pathology and histopathology revealed no abnormal findings in any COMT genotype. The values of some clinical chemistry parameters, such as alkaline phosphatase, alanine aminotransferase, urea, glucose, calcium and proteins, were at a higher level in homozygous animals compared with the wild-type mice. However, all the values remained within the normal physiological range, and the differences in enzyme levels between genotypes were not reflected as histopathological findings in the relevant organs. No changes in haematological parameters or plasma catecholamine concentrations were noted but plasma 3,4-dihydroxyphenylethylene glycol levels were high in COMT null mice. The results suggest that the full or 50% lack of Comt gene as such is not associated with any toxic consequences.
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PMID:Tissue histopathology, clinical chemistry and behaviour of adult Comt-gene-disrupted mice. 1288 3


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