Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The aim of the present study was to evaluate the influence of fluvastatin (3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor) on heterotopic ossification (HO) induced by HeLa cells. 2. C57Bl/6 mice were injected with 3 x 10(6) HeLa cells into right thigh muscles. Mice in the experimental group received fluvastatin 1.2 mg/kg per day for 17 consecutive days, while mice in the control group received placebo. Intact mice served as an additional control. Seventeen days post-HeLa cell grafting, blood samples were collected to measure total serum cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol and alkaline phosphatase (AP). 3. In all animals injected with HeLa cells, the mass of mineral deposited in the induced ossicle was established after hydrolysis of soft tissues surrounding the induced ossicles. In fluvastatin-treated mice, the mass of mineral deposited in heterotopically induced ossicles was significantly increased, when compared to mice receiving placebo. This was followed by a significant decrease of TG concentration; whereas the levels of serum AP were not significantly affected. 4. These results indicate that administration of statins may affect heterotopic ossification. This may also have clinical implication, because patients predisposed to HO and receiving statins during hypocholesterolemic treatment, may be at even greater risk of HO.
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PMID:Fluvastatin increases heterotopically induced ossicles in mice. 1662 Mar 6

Human cerebral malaria is caused by a protozoan parasitic with no cure till date. The isolation of brain capillaries i.e. microvessels has permitted the in vitro study related to cerebral function. Microvessels were isolated from normal and P. yoelii infected mice brain cortex and subjected to biochemical characterization by the following enzyme markers viz alkaline phosphatase, gamma-glutamyI transpeptidase and monoamine oxidase and electron microscopically. Limited studies have been carried out in relation to drug metabolizing enzymes in cerebral microvessels of rodents. The present studies have been carried out in relation to status of drug metabolizing enzymes during P. yoelii infection in cerebral microvessels of mice. The data obtained depicted a clear cut impairment of cytochrome P450 (a terminal monooxygenase) and related indices viz b5, benzopyrene hydroxylase, aminopyrene-n-demethylase, aniline hydroxylase except NADH cytochrome e reductase which increased during P. yoelii infection in mice as compared to normal. Further the oral drug administration (arteether) treatment brought back the altered MFO system normal a week alter cessation of drug treatment.
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PMID:Studies on drug metabolizing enzymes during arteether treatment of Plasmodium yoelii nigeriensis infected mice cerebral microvessels. 1663

Propolis, a natural beehive product has been known for centuries for a variety of beneficial traditional medicinal properties. The present study was conducted to ascertain the antineoplastic potential of propolis along with paclitaxel against experimental mammary carcinogenesis. Female Sprague Dawley rats at 55 days of age were treated with dimethylbenz(a)anthracene to induce breast cancer. Paclitaxel at a dose of 33 mg/kg body mass intraperitoneally and propolis 50 mg/kg body weight orally was administered to the experimental animals, immediately after the carcinogen treatment and continued until the termination of the study. At the end of the treatment activities of phase I and II xenobiotic metabolizing enzymes and liver marker enzymes were measured. A significant increase in carcinogen activating enzymes, cytochrome P(450), cytochrome b(5) and NADPH cytochrome C reductase with concomitant decrease in phase II enzymes, glutathione transferase and UDP-glucuronyl transferase were observed in animals with mammary cancer. Furthermore there was a significant decrease in alanine aminotransferase, aspartate aminotransferase with a sharp increase in alkaline phosphatase, acid phosphatase and 5' nucleotidase. Propolis treatment caused the activity of these enzymes return to almost normal control levels, indicating the protective effect of propolis against dimethyl benz(a) anthracene induced carcinogenesis. On the basis of the observed results propolis can be considered a promising chemotherapeutic agent and can be administered as an adjuvant with paclitaxel chemotherapy.
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PMID:Therapeutic effect of propolis and paclitaxel on hepatic phase I and II enzymes and marker enzymes in dimethylbenz(a)anthracene-induced breast cancer in female rats. 1672 Jan 5

Statins, which are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are widely used for the treatment of hyperlipidemia, and recent studies and animal data suggest that statins promote osteogenesis and increase bone strength. However, little is known about the effects of statins delivered by sustained delivery system to a target site of a defect and segmental bone fractures on certain biochemical markers including reproductive hormones. The purpose of this study was to develop a targeted statin delivery system using Tricalcium Phosphate Lysine (TCPL) for defect and segmental femoral injuries and evaluate the effects on alkaline phosphatase, total protein, malinodialdehyde, glutathione, total cholesterol, testosterone, luteinizing hormone, statins, and follicle-stimulating hormone. Because of the influence oral intake of statins might have on certain body organs, we also examine the histomorphology of the vital and reproductive organs of the animals receiving statins for a period of 30 days and 12 weeks post surgery. Simvastatin used in this study significantly increased fracture healing and without significant influence on the body weights and the weights and morphology of the vital and reproductive organs. There was a significant reduction in the cholesterol levels on the 3rd week in both phases of the study and at the conclusion of the study the difference in the cholesterol levels was no more significant in both phases. Other biochemical markers including plasma LH, FSH and testosterone levels were not affected by active treatment with simvastatin. In conclusion, short and long-term simvastatin treatment delivered at a fracture target site did not influence vital and reproductive organs, the systemic levels of the biochemical markers studied, but was able to effectively stimulate bone formation in simple and complicated segmental fractures.
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PMID:Effects of sustained release of statin by means of tricalcium phosphate lysine delivery system in defect and segmental femoral injuries on certain biochemical markers in vivo. 1681 97

The purpose of the present study was to assess the therapeutic effect of hypothermic retrograde jugular vein flush (HRJVF) on heatstroke. HRJVF was accomplished by infusion of 4 degrees C isotonic sodium chloride solution via the external jugular vein (1.7 mL/100 g of body weight over 5 min). Immediately after the onset of heatstroke, anesthetized rats were divided into 2 major groups and given the following: 36 degrees C or 4 degrees C isotonic sodium chloride solution, i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. When the 36 degrees C saline-treated rats underwent heat exposure, their survival time values were found to be 23 to 28 min. Immediately after the onset of heatstroke, resuscitation with an i.v. dose of 4 degrees C saline significantly improved survival during heatstroke (208-252 min). All heat-stressed animals displayed systemic inflammation and activated coagulation, evidenced by increased tumor necrosis factor alpha, prothrombin time, activated partial thromboplastin time, and d-dimer, and decreased platelet count and protein C. Biochemical markers evidenced cellular ischemia and injury/dysfunction: plasma levels of blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase; and striatal levels of glycerol, glutamate, and lactate/pyruvate; dihydroxy benzoic acid, lipid peroxidation, oxidized-form glutathione reduced-form glutathione, dopamine, and serotonin were all elevated during heatstroke. Core and brain temperatures and intracranial pressure were also increased during heatstroke. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and striatal levels of local blood flow, partial pressure of oxygen, superoxide dismutase, catalase, glutathione peroxidase, and glutathions reductase activities were all significantly lower during heatstroke. The circulatory dysfunction, systemic inflammation, hypercoagulable state, and cerebral oxidative stress, ischemia, and damage during heatstroke were all significantly suppressed by HRJVF. These findings demonstrate that brain cooling caused by HRJVF therapy may resuscitate persons who had a stroke by attenuating cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke.
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PMID:Brain cooling causes attenuation of cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke. 1687 31

Statins, the widely used lipid-lowering drugs, are inhibitors of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, which catalyses a rate-limiting step in the biosynthesis of cholesterol. Many previous reports show that statins can act both as bone anabolic and as anti-resorptive agents but their beneficial effects on bone turnover are still controversial. Considering their high liver specificity and low oral bioavailability, the distribution of statins to the bone microenvironment is questionable. In this study, the distribution of lovastatin and its active metabolites to bone, with respect to plasma and liver compartments, was examined after oral and intravenous administration in female rats. As compared with oral administration, the distribution of lovastatin to the bone compartment was significantly enhanced after intravenous administration. Further, the effect of lovastatin on bone turnover was studied in-vitro and in-vivo to assess its anti-osteoporotic potential. Lovastatin acid but not lovastatin was found to inhibit parathyroid-hormone-induced bone resorption in an in-vitro chick embryo bone assay. Oral, as well as intravenous, short-term lovastatin treatment significantly reduced the serum total cholesterol, serum total alkaline phosphatase and urinary crosslinks in ovariectomized rats. In accordance with its increased distribution to the bone compartment, intravenously administered lovastatin was more effective in reducing the ovariectomy-induced increase in markers of bone metabolism, especially urinary crosslinks. The findings of this study suggest that statins inhibit bone resorption and that their anti-resorptive efficacy can be increased by administering them by routes other than oral so as to achieve their enhanced concentration in bone.
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PMID:Distribution of lovastatin to bone and its effect on bone turnover in rats. 1713 7

No consensus has been reached on whether the 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, known as statins, have beneficial effects on bone health. The purpose of our study was to evaluate the effects of atorvastatin on bone metabolism by means of measuring bone turnover markers in male patients with hypercholesterolemia both at diagnosis and prospectively after 3 months of treatment. Twenty-two Japanese male patients (mean age 62.36 +/- 10.1 years) with untreated hypercholesterolaemeia were selected for this study. After 3-months treatment of atorvastatin, total cholesterol and low density lipoprotein cholesterol significantly decreased as expected (p<0.001 for both parameters). Bone-specific alkaline phosphatase (BAP) did not change significantly (p = 0.444). However, serum N-terminal telopeptide of type I collagen (NTx) significantly decreased by -19.86 +/- 26.4% (p = 0.020). In addition, delta NTx during the course of this study was negatively correlated with NTx at baseline (r = -0.645, p = 0.0008). Although there was a tendency of positive correlations of delta NTx with delta total cholesterol, delta triglycerides, and delta low density lipoprotein cholesterol, and of negative correlations of delta NTx and delta BAP with delta high density lipoprotein cholesterol, none of them reached statistical significance. Our findings suggest that atorvastatin may have potentially beneficial effects on bone metabolism in patients with hypercholesterolemia mostly by reducing bone resorption rather than by stimulating bone formation. Further studies with more patients and longer duration are warranted to evaluate its effects, if any, on prevention of osteoporosis and subsequent fractures.
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PMID:Short-term effects of atorvastatin on bone turnover in male patients with hypercholesterolemia. 1718 79

The present study investigates the hepatoprotective effect of fenugreek seed polyphenolic extract (FPEt) against ethanol-induced hepatic injury and apoptosis in rats. Chronic ethanol administration (6 g/kg/day x 60 days) caused liver damage that was manifested by the elevation of markers of liver dysfunction--aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin and gamma-glutamyl transferase (GGT) in plasma and reduction in liver glycogen. The effects on alcohol metabolizing enzymes such as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were studied and found to be altered in the alcohol-treated group. Ethanol administration resulted in adaptive induction of the activities of cytochrome p450 (cyt-p-450) and cytochrome-b5 (cyt-b5) and reduction in cytochrome-c-reductase (cyt-c-red) and glutathione-S-tranferase (GST), a phase II enzyme. Further, ethanol reduced the viability of isolated hepatocytes (ex vivo) as assessed by the trypan blue exclusion test and increased hepatocyte apoptosis as assessed by propidium iodide staining (PI). Treatment with FPEt restored the levels of markers of liver injury and mitigated the alterations in alcohol metabolizing and detoxification enzymes and the electron transport component cytochrome-c reductase. Increased hepatocyte viability and reduced apoptotic nuclei were observed in FPEt-treated rats. These findings demonstrate that FPEt acts as a protective agent against ethanol-induced abnormalities in the liver. The effects of FPEt are comparable with those of a known hepatoprotective agent, silymarin.
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PMID:Fenugreek (Trigonella foenum graecum) seed polyphenols protect liver from alcohol toxicity: a role on hepatic detoxification system and apoptosis. 1748 88

PDI enzymes are oxidoreductases that catalyze oxidation, reduction and isomerization of disulfide bonds in polypeptide substrates. We have previously identified an E. histolytica PDI enzyme (EhPDI) that exhibits oxidase activity in vivo. However, little is known about the specific role of its redox-related structural features on the enzymatic activity. Here, we have studied the in vivo oxidative folding of EhPDI by mutagenic analysis and functional complementation assays as well as the in vitro oxidative folding and reductive activities by comparative kinetics using functional homologues in standard assays. We have found that the active-site cysteine residues of the functional domains (Trx-domains) are essential for catalysis of disulfide bond formation in polypeptides and proteins, such as the bacterial alkaline phosphatase. Furthermore, we have shown that the recombinant EhPDI enzyme has some typical properties of PDI enzymes: oxidase and reductase activities. These activities were comparable to those observed for other functional equivalents, such as bovine PDI or bacterial thioredoxin, under the same experimental conditions. These findings will be helpful for further studies intended to understand the physiological role of EhPDI.
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PMID:Oxidative folding and reductive activities of EhPDI, a protein disulfide isomerase from Entamoeba histolytica. 1936 71

The marine diazotroph Trichodesmium is a major contributor to primary production and nitrogen fixation in the tropical and subtropical oceans. These regions are often characterized by low phosphorus (P) concentrations, and P starvation of Trichodesmium could limit growth, and potentially constrain nitrogen fixation. To better understand how this genus responds to P starvation we examined four genes involved in P acquisition: two copies of a high-affinity phosphate binding protein (pstS and sphX) and two putative alkaline phosphatases (phoA and phoX). Sequence analysis of these genes among cultured species of Trichodesmium (T. tenue, T. erythraeum, T. thiebautii and T. spiralis) showed that they all are present and conserved within the genus. In T. erythraeum IMS101, the expression of sphX, phoA and phoX were sensitive to P supply whereas pstS was not. The induction of alkaline phosphatase activity corresponded with phoA and phoX expression, but enzyme activity persisted after the expression of these genes returned to basal levels. Additionally, nifH (nitrogenase reductase; involved in nitrogen fixation) expression was downregulated under P starvation conditions. These data highlight molecular level responses to low P and lay a foundation for better understanding the dynamics of Trichodesmium P physiology in low-P environments.
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PMID:Molecular analysis of the phosphorus starvation response in Trichodesmium spp. 1955 81


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