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)

Male Sprague-Dawley rats, who had received 50 micrograms/ml of arsenic (as sodium arsenate) in drinking water for 320 days, showed high urinary excretion of this element. Arsenic was accumulated in tissues, mostly in the kidney and in the liver. In the kidney were evident slight focal alterations in tubules and glameruli; some of the tubules contained casts of amorphous hyaline material. The hepatocytes close to the centrolobular veins were swollen and showed ultrastructural alterations. The seric GOT, GPT and LDH activities were normal, while the alkaline phosphatase alto have been found in the brain, sciatic nerve, lung, heart and arteries. No significant changes of systolic and diastolic blood pressure levels were observed. Similarly, cardiac inotropism and chronotropism were unchanged. The electrocardiogram, also, was normal. The cardiovascular reactivity to noradrenaline, acetylcholine, histamine, serotonin, bradykinin and angiotensin II was unchanged. However, the vascular reactivity to the beta-stimulation was increased, while it was decreased to the angiotensin I. On the whole, our results suggest that chronic arsenic exposure produces focal alterations in the kidney and characteristic modifications in the hepatic structure and in the cardiovascular reactivity.
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PMID:[Chronic exposure to arsenic in rats: morphological and functional findings]. 676 36

The effects of meso 2, 3-dimercaptosuccinic acid (DMSA), sodium 2, 3-dimercaptopropane 1-sulfonate (DMPS) and S-adenosyl L-methionine (SAM) on the enzymatic activities of mice were studied. The mice were given intraperitoneal (i.p.) injections of these chelating agents (1 mmol/kg) and 3 h later the activity of delta-aminolevulinic acid dehydratase (ALAD) in the blood, and aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GT), alkaline phosphatase (ALP) in the liver and kidney were determined. The activity of blood ALAD was significantly increased by the administration of DMSA and SAM while DMPS had only a moderate effect. The activities of other hepatic enzymes changed little when the mice were treated with these chelating agents, except for a significant reduction in hepatic ALP activity following DMPS administration. Arsenic (III) administration markedly increased the activities of ALT and ALP in the liver and kidneys. The changes in the enzymatic activities by treatment with arsenic were prevented by injection of DMSA, DMPS and SAM, DMSA being the most effective. These results indicate that DMSA, DMPS and SAM were not toxic to the liver or kidneys of mice and that treatment with DMSA is more effective than DMPS or SAM in protecting mice from acute hepatic or renal toxicity caused by arsenic.
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PMID:Effects of some thiol chelators on enzymatic activities in blood, liver and kidneys of acute arsenic (III) exposed mice. 955 1

Splenic macrophages are highly efficient in trapping and concentrating foreign substances carried in the blood and also the major sites where antibodies are synthesised and from where they are released into the circulation. Lead and Arsenic as environmental agents are considered to be high priority toxic substances largely due to their carcinogenic potentials in humans. However, these heavy metals as carcinogens remain an enigma because while they are definitely active in humans, carcinogenesis in the rodent model has never been convincingly demonstrated. Although macrophages are predominantly recruited to the site of inflammation during inflammatory distress as well as in immune response, nothing is known about the interaction of lead and arsenic with macrophages and their possible role in immunotoxicologic effect. In the present study it is reported that in vivo lead acetate treatment (10 mg/kg body wt) inhibits the cell adhesion property and alters the cell morphology in the splenic macrophages. Results show that there is a significant decrease in alkaline phosphatase release in lead treated macrophages (6.7 +/- 0.88 IU/100 mL) with respect to control (14.17 +/- 0.18). In vivo exposure of sodium arsenite (0.5 mg/kg body wt) also decreases phagocytic activity for ingestion and digestion of exogenous antigens, such as whole microorganism, as evident from the phagocytic index, 11555.55 +/- 62.86 (in control) to 5555.5 +/- 1571.33 in arsenic treated cells. Arsenic exposed cells release 8.15 +/- 0.05 microM nitric oxide, whereas control cells release 10.95 +/- 0.15 microM of nitric oxide, which is also identical following LPS stimulation. Results show that the functional integrity of the target cell is also decreased after arsenic exposure as obtained from the percentage of DNA fragmentation. A greater percentage of DNA fragmentation upon arsenic treatment (43.1 +/- 0.05%) with respect to control (14.9 +/- 0.34%) indicates that arsenic induces apoptosis. In immune cells which are rapidly proliferating and differentiating, inhibition of these heavy metal induced functions may result in similar degree of toxicity and lead to diseased state.
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PMID:Effect of lead and arsenic on murine macrophage response. 1237 52

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

Exposure to inorganic arsenic in drinking water is linked to skin, lung and bladder cancer in humans. The mechanism of arsenic-induced cancer is not clear, but exposure to arsenic and polycyclic arylhydrocarbons (PAH) is more carcinogenic than exposure to either type of carcinogen alone. Arsenic can also generate reactive oxygen species, suggesting that oxidation of DNA may play a role in carcinogenesis. Oxidization of guanosines in polyG tracts is known to cause frameshift mutations, and such events can be detected in situ using the G11 placental alkaline phosphatase (PLAP) transgenic mouse model, which reports frameshift mutations in a run of 11 G:C basepairs by generating cells containing heat-resistant alkaline phosphatase activity. PAH can also induce frameshift mutations. In the study described here, FVB/N mice carrying the G11 PLAP transgene were crossed to C57Bl/6 mice. Half of the hybrid mice were given drinking water with sodium arsenite (10 mg/L) for 10 weeks. Half of the arsenic treated mice were also exposed to benzo[a]pyrene (BaP) by skin painting (500 nmol/week) for 8 weeks. Another group of mice was exposed to BaP but not arsenic. The effect on frameshift mutation was assessed by staining sections of skin tissue to detect cells with PLAP activity. Arsenic alone had no significant effect. On average, mice given BaP alone had approximately three times more PLAP-positive (PLAP+) cells. By contrast, mice exposed to both arsenic and BaP exhibited 10-fold more PLAP+ cells in the skin, and these cells were often arranged in large clusters, suggesting derivation from stem cells. Whereas combined treatment produced more PLAP+ cells, stable BaP adduct levels and arsenic burdens were not higher in mice exposed to both agents compared to mice exposed to either one agent or the other.
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PMID:Co-mutagenic activity of arsenic and benzo[a]pyrene in mouse skin. 1624 80

The present study deals with the therapeutic potential of combined administration of N-acetylcysteine (NAC) along with monoisoamyl DMSA (MiADMSA) against chronic arsenic poisoning in guinea pigs. Animal were exposed to 50 ppm arsenic in drinking water for 8 mo and subsequently treated for 5 consecutive days with 100 mg/kg NAC (orally) and MiADMSA (intraperitoneally), individually or in combination (50 mg/kg each). Arsenic exposure produced a significant depletion of blood delta- aminolevulinic acid dehydrate (ALAD) activity, increased the blood zinc protoporphyrin (ZPP) level, and reduced blood and liver glutathione (GSH) levels in guinea pigs. Hepatic oxidized glutathione (GSSG) and thiobarbituric acid reactive substance (TBARS) levels showed a marked increase, whereas hepatic alkaline phosphatase (ALP) activity decreased and acid phosphatase (ACP) activity increased on arsenic exposure. Significant depletion of liver transaminase activities on arsenic exposure suggests organ injury. Administration of MiADMSA, alone and in combination with NAC after arsenic exposure, was able to significantly enhance hepatic GSH and to reduce GSSG and TBARS levels compared to the arsenic control. Biochemical variables indicative of liver injury generally remained insensitive to any of these treatments. The recoveries in parameters indicative of oxidative stress were more marked in guinea pigs treated with combined administration of NAC and MiADMSA than monotherapy. Interestingly, there was a more pronounced depletion of arsenic from blood and tissues after combined treatment with NAC plus MiADMSA than MiADMSA. Blood and tissues copper, zinc, iron, and calcium concentrations showed a significant increase after arsenic exposure, which showed improvement, particularly after combined administration of MiADMSA and NAC. Based on these data, a proposal can be made that greater effectiveness in chelation treatment against chronic arsenic poisoning (i.e., turnover in the oxidative stress and removed of arsenic from the system) could be achieved by combined administration of an antioxidant (preferably having a thiol moiety) with MiADMSA.
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PMID:Combined administration of N-acetylcysteine and monoisoamyl DMSA on tissue oxidative stress during arsenic chelation therapy. 1667 47

Contamination of ground water by arsenic has become a cause of global public health concern. In West Bengal, India, almost 6 million people are endemically exposed to inorganic arsenic by drinking heavily contaminated groundwater through hand-pumped tube wells. No safe, effective and specific preventive or therapeutic measures for treating arsenic poisoning are available. We recently reported that some of the herbal extracts possess properties effective in reducing arsenic concentration and in restoring some of the toxic effects of arsenic in animal models. Moringa oleifera Lamarack (English: Horseradish-tree, Drumstick-tree, Hindi: Saijan, Sanskrit: Shigru) belongs to the Moringaceae family, is generally known in the developing world as a vegetable, a medicinal plant and a source of vegetable oil. The objective of the present study was to determine whether Moringa oleifera (M. oleifera) seed powder could restore arsenic induced oxidative stress and reduce body arsenic burden. Exposure to arsenic (2.5 mg/kg, intraperitoneally for 6weeks) led to a significant increase in the levels of tissue reactive oxygen species (ROS), metallothionein (MT) and thiobarbituric acid reactive substance (TBARS) which were accompanied by a decrease in the activities in the antioxidant enzymes such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in mice. Arsenic exposed mice also exhibited liver injury as reflected by reduced acid phosphatase (ACP), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) activities and altered heme synthesis pathway as shown by inhibited blood delta-aminolevulinic acid dehydratase (delta-ALAD) activity. Co-administration of M. oleifera seed powder (250 and 500 mg/kg, orally) with arsenic significantly increased the activities of SOD, catalase, GPx with elevation in reduced GSH level in tissues (liver, kidney and brain). These changes were accompanied by approximately 57%, 64% and 17% decrease in blood ROS, liver metallothionein (MT) and lipid peroxidation respectively in animal co-administered with M. oleifera and arsenic. Another interesting observation has been the reduced uptake of arsenic in soft tissues (55% in blood, 65% in liver, 54% in kidneys and 34% in brain) following administration of M. oleifera seed powder (particularly at the dose of 500 mg/kg). It can thus be concluded from the present study that concomitant administration of M. oleifera seed powder with arsenic could significantly protect animals from oxidative stress and in reducing tissue arsenic concentration. Administration of M. oleifera seed powder thus could also be beneficial during chelation therapy with a thiol chelator.
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PMID:Concomitant administration of Moringa oleifera seed powder in the remediation of arsenic-induced oxidative stress in mouse. 1705 7

This experiment was conducted to investigate the effect of dietary arsenic (As) levels on growth performance, serum biochemistry, and the retention of iron, copper, and zinc in tissues of growing and finishing pigs. Ninety-six crossbred pigs were randomly allotted to four dietary treatments. The corn-soybean basal diets were supplemented with 0, 10, 20, and 30 mg As/kg. Arsenic trioxide was used as the arsenic source. The feeding experiment lasted for 78 d. The results showed that the high arsenic diet decreased average daily gain (ADG) (p<0.05) and increased feed gain ratio (F/G) (p<0.05). Arsenic intake significantly increased (p<0.05) serum gamma-gultamyltransferase (GGT), glutamic-pyruvic transaminase (GPT), and alkaline phosphatase (ALP) activities, and decreased (p<0.05) total protein, urea nitrogen, creatinine, and triglycerides. Glutamic-oxalacetic transaminase (GOT) activity, albumin, and cholesterol were not affected (p>0.05). Arsenic feeding elevated (p<0.05) liver and kidney copper concentration, but reduced (p<0.05) copper concentration in heart, bile, and lymphaden of intestine mesentery. There were increases in iron levels in liver, bile, spleen, thymus, and pancreas in pigs fed the high As diets (p<0.05), but iron contents in kidney, heart, and serum were decreased by the arsenic treatment (p<0.05). Zinc concentrations were increased (p<0.05) in liver, kidney, and thymus of pigs with arsenic treatment, but decreased (p<0.05) in bile and lymphaden of intestine mesentery. This study suggested that high dietary As levels could alter serum biochemical parameters and the retention of copper, iron, and zinc in the viscera of growing and finishing pigs.
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PMID:Effects of dietary arsenic levels on serum parameters and trace mineral retentions in growing and finishing pigs. 1719 18

We studied the hepatocellular alterations induced by sub-lethal concentrations (0.50 muM) of arsenic in Indian catfish Clarias batrachus L. Sub-lethal arsenic exposure altered serum aspartate aminotransferase and alkaline phosphatase levels and brought about significant changes in different serum biochemical parameters. Arsenic exposure reduced total hepatocyte protein content and suppressed the proliferation of hepatocytes in a time-dependent manner. Routine histological studies on liver documented arsenic-induced changes characterized by dilated sinusoids, formation of intracellular edema, megalocytosis, vacuolation and appearance of hepatic cells with distorted nuclei. Transmission electron microscopy of hepatocytes further revealed hyperplasia and hypertrophy of mitochondria, development of dilated rough endoplasmic reticulum and changes in peroxisome size with duration of arsenic exposure. Degeneration of mitochondrial cristae and condensation of chromatin was also evident in arsenic-exposed hepatocytes. A significant number of hepatocytes isolated from arsenic-exposed fish stained with annexin V and demonstrated DNA ladder characteristic of apoptosis. Single-cell gel electrophoresis of exposed hepatocytes also revealed the development of comets usually seen in apoptotic cells. Using specific inhibitors it was determined that the arsenic-induced apoptosis of hepatocytes was caspase-mediated, involving the caspase 3 pathway.
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PMID:Sub-lethal concentration of arsenic interferes with the proliferation of hepatocytes and induces in vivo apoptosis in Clarias batrachus L. 1733 63

Arsenic is a potent environmental toxin. Present study has been designed to evaluate the protective role of taurine (2-aminoethanesulfonic acid) against arsenic induced cytotoxicity in murine hepatocytes. Sodium arsenite (NaAsO(2)) was chosen as the source of arsenic. Incubation of hepatocytes with the toxin (1 mM) for 2 h reduced the cell viability as well as intra-cellular antioxidant power. Increased activities of alanine transaminase (ALT) and alkaline phosphatase (ALP) due to toxin exposure confirmed membrane damage. Toxin treatment caused reduction in the activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx). In addition, the same treatment reduced the level of glutathione (GSH), elevated the level of oxidized glutathione (GSSG) and increased the extent of lipid peroxidation. Incubation of hepatocytes with taurine, both prior to and in combination with NaAsO(2), attenuated the extent of lipid peroxidation and enhanced the activities of enzymatic as well as non enzymatic antioxidants. Besides, taurine administration normalized the arsenic-induced enhanced levels of the marker enzymes ALT and ALP in hepatocytes. The cytoprotective activity of taurine against arsenic poisoning was found to be comparable to that of a known antioxidant, vitamin C. Combining all, the results suggest that taurine protects mouse hepatocytes against arsenic induced cytotoxicity.
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PMID:Taurine, a conditionally essential amino acid, ameliorates arsenic-induced cytotoxicity in murine hepatocytes. 1762 16


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