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)

The euryhaline fish, Oreochromis mossambicus was exposed to sub-lethal concentration (1.15 mg l(-1)) of a organophosphorus insecticide, monocrotophos (MCP) for 30 days and allowed to recover for seven days. Alanine aminotransferase (ALAT), aspartate aminotransferase (AAT), acid phosphatase (AcP), alkaline phosphatase (ALP), glycogen, lactate dehydrogenase (LDH), Reduced glutathione (GSH), gluthathione-S-transferase (GST) and acetylcholinesterase (AChE), were assayed in plasma and different tissues at regular intervals of day -3, -7, -15, -30 and after recovery period of seven days. The ALAT and AAT activities were increased in plasma and kidney, where as liver and gill showed decrease. Increase in AcP and ALP activities were observed in plasma, gill and kidney, and reduction of 42% and 50% was observed in liver. Glycogen was depleted in plasma, liver and gill indicates of typical stress related response of the fish with pesticide. LDH activity was decreased in liver and muscle, indicating tissue damage and muscular harm, but a significant increase in LDH activity in gill and brain was observed. Depletion in GSH activity was observed in all the tissues, there by enhancing the lipid peroxidation resulting in cell damage. The induction in hepatic GST levels indicates the protection against the toxicity of xenobiotic-induced lipid peroxidation. There was a significant recovery in all the above biochemical parameters studied in plasma and different tissues, after seven days recovery period. These results revealed that MCP affects the intermediary metabolism of O. mossambicus and that the assayed enzymes can work as good biomarkers of organophosphorus contamination.
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PMID:Biochemical alterations in euryhaline fish, Oreochromis mossambicus exposed to sub-lethal concentrations of an organophosphorus insecticide, monocrotophos. 1673 Jul 77

The effect of exposure to sublethal concentrations (0.017 mg L(-1), 1/10 of LC50) of the novel organophosphate (OP) insecticide, 2-butenoic acid-3-(diethoxyphosphinothioyl) methyl ester (RPR-II) on biochemical parameters in Oreochromis mossambicus was studied during exposure for 3, 7, 15, 30 and its recovery response after seven days. Acetylcholinesterase (AChE) activity of brain, gill and muscle was inhibited by 67%, 77% and 73% respectively on day-30. The plasma and kidney alanine aminotransferase (AlaAT), and aspartate aminotransferase (AspAT) activity increased, while decreases were observed in gill and liver. Increases in acid phosphatase (AcP), and alkaline phosphatase (AP) activities were observed in plasma, gill, and kidney, and reductions of 20% and 61% in liver AcP and AP, respectively. Depletion of glycogen was observed in all tissues, an indication of typical stress related response of the fish with pesticide. Lactate dehydrogenase (LDH) activity decreased in liver and muscle, indicating tissue damage but a significant increase in LDH activity in gill and brain was observed. Depletion of glutathione (GSH) was observed in all tissues, thereby enhancing lipid peroxidation resulting in cell damage. The induction in hepatic glutathione-S-transferase (GST) levels indicates protection against the toxicity of xenobiotic-induced lipid peroxidation. There was a significant recovery in the above biochemical parameters, in all tissues of fish after a recovery period of seven days. These results revealed that the OP insecticide RPR-II is highly toxic and affects the intermediary metabolism of O. mossambicus.
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PMID:Sublethal effects of an organophosphorus insecticide (RPR-II) on biochemical parameters of tilapia, Oreochromis mossambicus. 1676 96

Cigarette smoke contains low levels of agonists for the aryl hydrocarbon receptor (AhR; also called the dioxin receptor). However, little is understood about the whole potential of cigarette smoke for activating AhR. In this report, we evaluated the total "dioxin-like" activity of cigarette smoke using in vitro and in vivo reporter systems. Cigarette smoke extract (CSE) was prepared from seven cigarette brands (1-20 mg tar content) and subjected to in vitro bioassay based on the xenobiotic-responsive element (XRE) as the sensor and secreted alkaline phosphatase (SEAP) as the reporter. Exposure of reporter cells to CSE triggered activation of XRE in a dose-dependent manner, which was suppressed by functional inhibition of AhR. Direct, brief exposure of the cells to cigarette smoke similarly induced activation of XRE. Using 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) as the standard, the XRE-activating potential (XAP) of individual smoke was evaluated quantitatively. Positive correlation was observed between the tar content and XAP values. The XAP values estimated were extremely high with a range from 18.5 to 51.2 ng 2,3,7,8-TCDD equivalent per cigarette. To further estimate XAP of cigarette smoke in vivo, we generated transgenic reporter mice that secrete SEAP under the control of XRE. After exposure of the mice to smoke, serum levels of SEAP were significantly elevated within 12 hours, peaked at 24 hours, and declined thereafter. These results evidenced for the first time that cigarette smoke has unexpectedly high dioxin-like potential that triggers the AhR-XRE pathway in vitro and in vivo.
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PMID:High levels of dioxin-like potential in cigarette smoke evidenced by in vitro and in vivo biosensing. 1684 60

The effect of oxfendazole (OX), a benzimidazole anthelmintic, on hepatic gene expression was investigated in the liver of rats as a preliminary study to elucidate the possible mechanism of its non-genotoxic hepatocarcinogenesis. The liver from a male F344/N rat given a diet containing 500 ppm of OX for 3 weeks was examined by global gene expression analysis in comparison with an untreated rat. Microarray analysis revealed that phase I and phase II detoxifying enzymes were up-regulated in an OX-treated rat. In addition to these genes, the expressions of several upregulated genes related to xenobiotic metabolism and oxidative stress [e.g. Cyp1a1; NAD(P)H dehydrogenase, quinone 1 (Nqo1); glutathione peroxidase 2 (Gpx2); glutathione S-transferase Yc2 subunit (Yc2)], were confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR). Furthermore, rats were administered 500 or 1,000 ppm of OX for 9 weeks, and the effect of OX on oxidative stress responses was evaluated by real-time RT-PCR along with conventional toxicological assays, including lipid peroxidation (thiobarbituric acid-reactive substance; TBARS). A longer treatment period and/or a higher dose of OX tended to increase the gene expressions of not only phase I (Cyp1a1 and Cyp1a2) but also phase II (Nqo1, Gpx2, Yc2, and Akr7a3) drug metabolizing enzymes. Toxicological parameters, such as TBARS, serum aspartate aminotransferase (AST), and serum alkaline phosphatase (ALP), showed slight but significant increases after treatment with OX for 9 weeks. These results indicate that OX elicits adaptive responses against oxidative stress in the liver and suggest that the imbalance in redox status might be one of the factors triggering the initial step of OX-induced non-genotoxic carcinogenesis in the liver of rats.
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PMID:Gene expression analyses of the liver in rats treated with oxfendazole. 1734 Jan 21

A large number of xenobiotics are reported to be potentially hepatotoxic. Free radicals generated from the xenobiotic metabolism can induce lesions of the liver and react with the basic cellular constituents - proteins, lipids, RNA and DNA. Hepatoprotective activity of aqueous ethanol extract of Zingiber officinale was evaluated against single dose of acetaminophen-induced (3g/kg, p.o.) acute hepatotoxicity in rat. Aqueous extract of Z. officinale significantly protected the hepatotoxicity as evident from the activities of serum transaminase and alkaline phosphatase (ALP). Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and ALP activities were significantly (p<0.01) elevated in the acetaminophen alone treated animals. Antioxidant status in liver such as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase and glutathione-S-transferase (GST), a phase II enzyme, and levels of reduced glutathione (GSH) were declined significantly (p<0.01) in the acetaminophen alone treated animals (control group). Hepatic lipid peroxidation was enhanced significantly (p<0.01) in the control group. Administration of single dose of aqueous extract of Z. officinale (200 and 400mg/kg, p.o.) prior to acetaminophen significantly declines the activities of serum transaminases and ALP. Further the hepatic antioxidant status was enhanced in the Z. officinale plus acetaminophen treated group than the control group. The results of the present study concluded that the hepatoprotective effect of aqueous ethanol extract of Z. officinale against acetaminophen-induced acute toxicity is mediated either by preventing the decline of hepatic antioxidant status or due to its direct radical scavenging capacity.
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PMID:Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status. 1763 89

Silymarin, a standardized extract of the milk thistle (Silybum marianum), has a long tradition as a herbal remedy, and was introduced as a hepatoprotective agent a few years ago. However, the therapeutic effects of silymarin remain undefined. Carbon tetrachloride (CCl4) is a xenobiotic used extensively to induce oxidative stress and is one of the most widely used hepatic toxins for experimental induction of liver fibrosis in the laboratory. In this study, we investigated the restoration of the CCl4-induced hepatic fibrosis by high dose of silymarin in rats. After treatment with oil (as normal group; n = 6) or CCl4 [as model (n = 7) and therapeutic (n = 7) groups] by intragastric delivery for 8 weeks for the induction of liver fibrosis, the rats in the normal and model group were administered orally normal saline four times a week for 3 weeks whilst the therapeutic group received silymarin (200 mg/kg). The histopathological changes were observed with Masson staining. The results showed that the restoration of the CCl4-induced damage of liver fibrosis in the therapeutic group was significantly increased as compared to that in the model group. Moreover, silymarin significantly decreased the elevation of aspartate aminotransferase (AST), alanine aminotransferase, and alkaline phosphatase in serum, and also reversed the altered expressions of alpha-smooth muscle actin in liver tissue. Therefore, these findings indicated that silymarin may have the potential to increase the resolution of the CCl4-induced liver fibrosis in rats.
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PMID:Effects of silymarin on the resolution of liver fibrosis induced by carbon tetrachloride in rats. 1839 25

Concurrent use of more than one antibiotic in clinical treatment of serious infections is common. Trospectomycin sulphate, a semi-synthetic aminocyclitol, may be used in combination with the aminoglycoside gentamicin sulphate. To investigate any potential interaction, trospectomycin and gentamicin toxicity were assessed in vitro using a two-factor response surface design study with each factor at four levels. Cultures of the LLC-PK(1) cell line (proximal renal epithelium) were treated with 0, 125, 250 or 500 mug/ml of the drugs, alone or in combination, and cytotoxicity was evaluated at 3, 7, 10 and 14 days of continuous exposure. Cytotoxicity was assessed by morphological and biochemical criteria (lactate dehydrogenase, LDH; alkaline phosphatase, ALP; gamma-glutamyl transpeptidase, GGT; aspartate transaminase, AST; alanine transaminase, ALT; acid phosphatase, ACP). ALP, GGT, LDH and AST activity increased in the control cultures over the experimental period. Cytoplasmic vacuolation, increased number of detached cells and reduced dome formation occurred at 250 and 500 mug gentamicin/ml and in combination with these levels of trospectomycin at study days 10 and 14. There was a statistically significant (P < 0.05) interaction (decrease) for ALP and GGT at study day 14. In summary, the LLC-PK(1) culture system provides a useful in vitro screen to evaluate potential xenobiotic interactions to assess nephrotoxicity.
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PMID:In vitro assessment of trospectomycin and gentamicin sulphate in the LLC-PK(1) cell line. 2073 59

To investigate the presence and localization of a variety of xenobiotic biotransforming isozymes of the cytochrome P-450 superfamily in the organogenesis-stage rat conceptal tissue, pregnant female rats were dosed with one of two inducing agents, 3-methylcholanthrene [3MC, 40 mg/kg body weight, ip, day 7 post coitum (pc)] and phenobarbital (PB, 40 mg/kg, ip, days 5, 6, 7 and 8 pc), or with their vehicles (3MC, olive oil; PB, 0.9% NaCl) as controls. The conceptuses were allowed to grow either in vivo, or in vitro, using the whole embryo culture system, from days 9.5 to 11.5 pc. The embryos and isolated visceral yolk sacs were submitted to immunohistochemical investigation using light microscopy. The livers of the dams served as positive controls. Polyclonal and monoclonal antibodies raised against a variety of cytochrome P-450 isozymes were used in the alkaline phosphatase-anti-alkaline phosphatase enzyme immune complex method. All pre-induced dam livers showed positive staining with all polyclonal and monoclonal antibodies tested. The presence of P450IA1 was detected in the visceral yolk sac of both ex vivo and cultured conceptuses, preinduced in utero with 3MC, with the appropriate polyclonal antibodies but not with the monoclonal antibodies. P450IIB1/2 was detected in the visceral yolk sac of both ex vivo and cultured conceptuses, pre-induced in utero by phenobarbital, with the appropriate polyclonal antibodies, but not with the monoclonal antibodies. No staining was seen in any embryo proper, with any vehicle-treated conceptal tissue, or with antibodies raised against P-450s IIE1, IIIA or IVA. Our results support the hypothesis that the organogenesis-stage rat conceptus contains, in the visceral yolk sac, a 3MC-inducible P-450 isozyme similar, but not identical, to adult IA1. They also provide evidence that a PB-inducible isozyme similar, but not identical, to adult IIB1/2, is present in the visceral yolk sac at this stage of conceptus development.
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PMID:An immunohistochemical investigation into the presence and localization of cytochrome P-450 isozymes in organogenesis-stage rat conceptal tissue. 2073 68

The steroid and xenobiotic receptor (SXR) and its murine ortholog pregnane X receptor (PXR) are nuclear receptors that are expressed mainly in the liver and intestine where they function as xenobiotic sensors. In addition to its role as a xenobiotic sensor, previous studies in our laboratories and elsewhere have identified a role for SXR/PXR as a mediator of bone homeostasis. Here, we report that systemic deletion of PXR results in marked osteopenia with mechanical fragility in female mice as young as 4 months old. Bone mineral density (BMD) of PXR knockout (PXRKO) mice was significantly decreased compared with the BMD of wild-type (WT) mice. Micro-computed tomography analysis of femoral trabecular bones revealed that the three-dimensional bone volume fraction of PXRKO mice was markedly reduced compared with that of WT mice. Histomorphometrical analysis of the trabecular bones in the proximal tibia showed a remarkable reduction in bone mass in PXRKO mice. As for bone turnover of the trabecular bones, bone formation is reduced, whereas bone resorption is enhanced in PXRKO mice. Histomorphometrical analysis of femoral cortical bones revealed a larger cortical area in WT mice than that in PXRKO mice. WT mice had a thicker cortical width than PXRKO mice. Three-point bending test revealed that these morphological phenotypes actually caused mechanical fragility. Lastly, serum levels of phosphate, calcium, and alkaline phosphatase were unchanged in PXRKO mice compared with WT. Consistent with our previous results, we conclude that SXR/PXR promotes bone formation and suppresses bone resorption thus cementing a role for SXR/PXR as a key regulator of bone homeostasis.
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PMID:Pregnane X receptor knockout mice display osteopenia with reduced bone formation and enhanced bone resorption. 2087 38

Many phytochemicals are known to exert cancer chemopreventive activity by eliminating chemical carcinogens or toxic xenobiotics through the action of detoxification enzymes. In this study, we investigated the cancer chemopreventive effects of youngiasides isolated from Crepidiastrum denticulatum. These youngiasides significantly induced quinone reductase (QR) activity in mouse hepatoma Hepa-1c1c7 cells, and showed a relatively high chemoprevention index (CI; divided IC(50) value with CD value). The youngiasides also significantly induced transcriptional activation of QR in Hepa-QR-secreted alkaline phosphatase (SEAP) cells, which is a stable cell line containing the intact promoter region of QR. In order to determine if upregulation of QR by the youngiasides was mediated through a mono-functional or bi-functional mechanism, we examined the nuclear factor-E2 p45-related factor 2(Nrf2)-antioxidant response element (ARE) and aryl hydrocarbon receptor (AhR)-xenobiotic response element (XRE) pathways, which are two major pathways, involved in regulation of Phase I and/or Phase II detoxification enzymes. The youngiasides increased the cytochrome P450 1A1 (CYP1A1) mRNA and protein levels in human colorectal cancer Caco-2 cells and also increased the QR mRNA and protein levels in Caco-2 cells through ARE and XRE activation which resulted from translocation of Nrf2 and AhR into the nucleus. These results suggest that regulation of QR by the youngiasides was due to bi-functional induction through the Nrf2-ARE and AhR-XRE pathways. Thus, these youngiasides as bi-functional inducers of QR have potential as cancer chemopreventive agents.
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PMID:Bi-functional induction of the quinone reductase and cytochrome P450 1A1 by youngiasides via Nrf2-ARE and AhR-XRE pathways. 2093 Mar 71


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