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)

The purpose of this study was to test the hypothesis that acetaminophen would alter an estrogen-regulated process in human cells that express endogenous estrogen receptor alpha and beta (ERalpha and ERbeta). Specifically, the extent to which acetaminophen altered the expression of estrogen-inducible alkaline phosphatase in endometrial adenocarcinoma (Ishikawa) cells and directly interacted with ERbeta and ERalpha was determined. Ishikawa cells were exposed to estradiol and/or to a range of concentrations of acetaminophen for four days, and alkaline phosphatase activity was measured spectrophotometrically. Acetaminophen inhibited both basal and estradiol-induced alkaline phosphatase activity in Ishikawa cells in a concentration-dependent manner. The reduction of Ishikawa cell alkaline phosphatase was not due to direct inhibition of enzyme activity by acetaminophen. Toxic effects of acetaminophen on Ishikawa cells were determined by measuring loss of cellular lactate dehydrogenase to culture medium. High concentrations of acetaminophen (>/=0.5 mM) induced lactate dehydrogenase release from cells and reduced the amount of cellular protein in culture dishes, indicating some acetaminophen-induced reduction of alkaline phosphatase activity might be attributed to toxic effects. However, lower concentrations of acetaminophen significantly reduced alkaline phosphatase activity in the absence of detectable toxicity. Acetaminophen also augmented 4-hydroxy-tamoxifen reduction of alkaline phosphatase activity. Competition binding assays with human ERalpha and ERbeta demonstrated 10(6)-fold molar excess acetaminophen did not directly interact significantly with the ligand-binding domain of either receptor. These studies indicate acetaminophen exerts weak antiestrogenic activity in Ishikawa cells without directly binding ERalpha or ERbeta.
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PMID:Acetaminophen exhibits weak antiestrogenic activity in human endometrial adenocarcinoma (Ishikawa) cells. 1260 34

Acetaminophen is used as an analgesic and antipyretic. Due to its relative safety at therapeutic dose, it is frequently used in children and in pregnant women. We evaluated the effect of a dose equivalent to the therapeutic dose of Acetaminophen in undernourished rats; 72 Wistar male rats of 18 weeks of age, with weight between 270 and 280 g, were distributed randomly in four groups: A, normal without food restriction; B, normal without food restriction treated with Acetaminophen (100 mg/kg); C; undernourished by food restriction and D, undernourished by food restriction treated with Acetaminophen (100 mg/kg). The results showed decreasing of body and hepatic weight in undernourished rats and in undernourished treated with Acetaminophen, significant decrease of serum albumin concentration (p < 0.001). It was demonstrated that activity of the enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase significantly decreased (p < 0.001) in the group of undernourished rats treated with Acetaminophen compared with the other groups. We concluded that the Acetaminophen induces hepatic lesions in undernourished rats treated with a single non toxic dose of 100 mg/kg of weight, probably as a consequence of the inherent susceptibility to malnutrition.
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PMID:[Modification of liver enzymes in undernourished rats treated with acetaminophen]. 1463 61

The effect of oral administration of methanolic extract of Asteracantha longifolia (AL) seeds on acetaminophen (APAP)-induced acute liver damage in rats was investigated. The activities of marker enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma glutamyl transferase) and bilirubin level in serum and the levels of cholesterol, triglycerides, and free fatty acids in both serum and liver were found to be increased when rats were challenged with APAP. This was also associated with a significant reduction of serum and tissue phospholipids. Pretreatment with AL extract prior to the administration of APAP prevented these alterations as evidenced by liver histopathology. Results indicated that the extract could offer protection against APAP-induced liver damage, suggesting its hepatoprotective activity.
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PMID:Evaluation of the protective efficacy of Asteracantha longifolia on acetaminophen-induced liver damage in rats. 1529 74

Enzyme levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and alkaline phosphatase (ALP) increased following paracetamol induction were significantly lowered due to pretreatment with the beta-carotene (BC). This supplementation reversed the trend inducing a significant decrease in bilirubin and urea levels. Paracetamol administration significantly reduced hepatic glycogen, glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPX) and glutathione reductase (GSH-R). Pretreatment of rats with BC significantly increased the enzyme activities. The results suggest hepatoprotective activity of BC.
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PMID:Antihepatotoxic effect of beta-carotene on paracetamol induced hepatic damage in rats. 1587 20

The aim of this study was to investigate the hepatoprotective action of the protein fraction of Phyllanthus niruri against acetaminophen (APAP) hepatotoxicity. The partially purified protein fraction of P. niruri was injected intraperitoneally in mice either prior to (preventive) or after the induction of toxicity (curative). Levels of different liver marker enzymes in serum and different antioxidant enzymes, as well as lipid peroxidation in total liver homogenates were measured in normal, control (toxicity induced) and P. niruri protein fraction-treated mice. P. niruri significantly reduced the elevated glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) levels in the sera of toxicity induced mice, compared with the control group. Lipid peroxidation levels were also reduced in mice treated with P. niruri protein fraction compared with the APAP treated control group. Among the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST) levels were restored to almost normal levels compared with the control group. P. niruri treatment also enhanced reduced hepatic glutathione (GSH) levels caused by APAP administration. The results demonstrated that the protein fraction of P. niruri protected liver tissues against oxidative stress in mice, probably acting by increasing antioxidative defense.
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PMID:The protein fraction of Phyllanthus niruri plays a protective role against acetaminophen induced hepatic disorder via its antioxidant properties. 1671 36

Vernonia amygdalina Del. (Family Compositae) is used in Nigerian folk medicine as a tonic and remedy against constipation, fever, high blood pressure, and many infectious diseases. We have evaluated the hepatoprotective and antioxidant effects of an aqueous extract of V. amygdalina leaves against acetaminophen-induced hepatotoxicity and oxidative stress in mice in vivo. Activities of liver marker enzymes in serum (glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, lactate dehydrogenase, and alkaline phosphatase) and bilirubin levels were determined colorimetrically, while catalase activity, lipid peroxidation products, thiobarbituric acid-reactive substances (TBARS), iron, and total protein concentrations were measured in liver homogenate. Acetaminophen challenge (300 mg/kg, i.p) for 7 days caused significant (P < .01) increases in the levels of bilirubin, liver enzymes, TBARS, and iron, while catalase activity and total protein level were reduced significantly (P < .01). Preadministration of V. amygdalina resulted in a dose-dependent (50-100 mg/kg) reversal of acetaminophen-induced alterations of all the liver function parameters by 51.9-84.9%. Suppression of acetaminophen-induced lipid peroxidation and oxidative stress by the extract was also dose-dependent (50-100 mg/kg). The results of this study suggest that V. amygdalina elicits hepatoprotectivity through antioxidant activity on acetaminophen-induced hepatic damage in mice.
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PMID:Hepatoprotective and antioxidant activities of Vernonia amygdalina on acetaminophen-induced hepatic damage in mice. 1720 40

Acetaminophen (APAP) is a widely-used analgesic and a known hepatotoxic agent. Vascular endothelial growth factor (VEGF) is a growth factor with multiple functional roles. VEGF plays an important role in angiogenesis and hepatic regeneration. The aim of this study was to determine the expression of VEGF isoforms and its receptors throughout liver regeneration after the administration of a toxic dose of APAP in rats. Ten groups of adult male rats received a dose of 3.5 g/kg b.w. of APAP per os. The rats were killed post administration at 0-288 h. Blood and liver tissue were extracted. Determination of serum transaminases and alkaline phosphatase activities was performed. Liver injury and regeneration were assessed with hematoxylin-eosin specimens, morphometric analysis, hepatic thymidine kinase assay and Ki-67 expression. Reverse transcription-polymerase chain reaction and immunohistochemical methods were used for assessment of VEGF isoforms and receptors differential expression. High activities of aspartate aminotransferase were observed at 24 and 36 h with another peak of activity at 192 h post administration. Alanine aminotransferase was highest at 36 h. Alkaline phosphatase was increased post 24 h being higher at 72,192 and 240 h. Centrilobular necrosis was observed at 48-72 h and thorough restoration of the liver microarchitecture was observed at 288 h. Liver regeneration lasted from 24-192 h according to the results from thymidine kinase activity and Ki-67 expression. VEGF and VEGF receptor-2 m-RNA levels presented with a three-peak pattern of expression at 12-24, 72-96 and 192-240 h post administration. Significant difference was noted between periportal and centrilobular immunohistochemical expression. VEGF proves to play a critical role during APAP-induced liver regeneration as it presents with three points of higher expression. The first two time points are associated with the initial inflammatory reaction to the noxious stimulus and the hepatocyte regenerative process where as the third one is indicative of the potential involvement of VEGF in processes of remodeling.
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PMID:VEGF isoforms and receptors expression throughout acute acetaminophen-induced liver injury and regeneration. 1743 90

Methanolic extract of Phyllanthus-polyphyllus was evaluated for hepatoprotective and antioxidant activities in rats. The plant extract (200 and 300 mg/kg, p.o.) showed a remarkable hepatoprotective and antioxidant activity against acetaminophen induced hepatotoxicity as judged from the serum marker enzymes and antioxidant levels in liver tissues. Acetaminophen induced a significant rise in aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO) with a reduction of total protein, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione S-transferase (GST). Treatment of rats with different doses of plant extract (200 and 300 mg/kg) significantly (P<0.001) altered serum marker enzymes and antioxidant levels to near normal against acetaminophen treated rats. The activity of the extract at dose of 300 mg/kg was comparable to the standard drug, silymarin (50 mg/kg, p.o.). Histopathological changes of liver sample were compared with respective control. Results indicate the hepatoprotective and antioxidant properties of Phyllanthus polyphyllus against acetaminophen-induced hepatotoxicity in rats.
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PMID:Protective effect of Phyllanthus polyphyllus on acetaminophen induced hepatotoxicity in rats. 1816 21

Initiation of acetaminophen (APAP) toxicities is believed to be promoted by oxidative stress during the event of overdosage. The aim of the present study was to evaluate the hepatoprotective action of Moringa oleifera Lam (MO), an Asian plant of high medicinal value, against a single high dose of APAP. Groups of five male Sprague-Dawley rats were pre-administered with MO (200 and 800 mg/kg) prior to a single dose of APAP (3g/kg body weight; p.o). Silymarin was used as an established hepatoprotective drug against APAP induced liver injury. The hepatoprotective activity of MO extract was observed following significant histopathological analysis and reduction of the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in groups pretreated with MO compared to those treated with APAP alone. Meanwhile, the level of glutathione (GSH) was found to be restored in MO-treated animals compared to the groups treated with APAP alone. These observations were comparable to the group pretreated with silymarin prior to APAP administration. Group that was treated with APAP alone exhibited high level of transaminases and ALP activities besides reduction in the GSH level. The histological hepatocellular deterioration was also evidenced. The results from the present study suggested that the leaves of MO can prevent hepatic injuries from APAP induced through preventing the decline of glutathione level.
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PMID:Moringa oleifera Lam prevents acetaminophen induced liver injury through restoration of glutathione level. 1851 95

We have addressed in the current study the postulate whether or not carnitine deficiency would represent a risk factor in hepatotoxicity. Carnitine-deficient male Swiss albino rats were obtained following administration of D-carnitine (500 mg/kg, IP) for 10 consecutive days. Serum and liver carnitine levels, both total and free, were assessed to confirm carnitine depletion. Hepatotoxicity was induced by challenging animals with a single dose of paracetamol (1 g/kg, IP). Serum tumor necrosis factor (TNF-alpha) concentration, and serum activities of aspartate amino transferase (AST), alanine amino transferase (ALT) and alkaline phosphatase (ALP) were undertaken as biomarkers for toxicity. Liver contents of reduced glutathione (GSH), malondialdehyde (MDA), total nitric oxide (NO) and myeloperoxidase (MPO) activities were also investigated. Histopathological examination of liver sections was achieved to confirm the biochemical alterations. D-carnitine altered all biochemical markers and also induced mild tissue inflammation with dilatation and congestion of central and portal veins. Paracetamol produced an obvious hepatotoxicity model that was well characterized biochemically and morphologically. Combined administration of D-carnitine and paracetamol synergistically provoked marked toxicity that was more profound than either agent given alone. The present work was further extended to elucidate any hepatoprotective effect of carnitine supplementation in such toxicity paradigm. It was apparent that L-carnitine notably ameliorated all biochemical markers and also mitigated the gross histologic alterations induced by paracetamol. Data obtained so far would suggest that carnitine deficiency could possibly be a sequela as well as a causative clue for paracetamol hepatotoxicity.
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PMID:Carnitine deficiency: a possible risk factor in paracetamol hepatotoxicity. 1859 74


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