Possible Induction of Cholinesterase in Epileptic Patients Treated With Anticonvulsant Drugs: Relationship With Lipoprotein Levels

Tutor-Crespo, María J.; Hermida, Jesús; Tutor, J. Carlos

doi:10.1177/0091270004266486

Cited by 6 publications

(3 citation statements)

References 41 publications

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“…However, other studies found no changes in serum Zn concentration in epileptic patients compared with the control group as described in some studies. 9 , 15 , 16 , 17 On the other hand, Hamed et al 18 demonstrated that the untreated epileptics exhibited unaltered Zn levels and sodium valproate treated epileptics showed significantly higher levels of Zn ( p <0.05). The real mechanism of the possible effect of AEDs on Zn concentrations is not completely understood, valproate binds Zn protects GABA from the inhibitory effect of Zn; hence, increased level of GABA.…”

Section: Discussionmentioning

confidence: 99%

Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants

Talat

Ahmed

Mohammed

2015

NSJ

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Objective:To evaluate the serum levels of zinc and copper in epileptic children during the long-term treatment of anticonvulsant drugs and correlate this with healthy subjects.Methods:A hospital-based group matched case-control study was conducted in the Department of Pediatrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt between November 2013 and October 2014. Ninety patients aged 7.1±3.6 years were diagnosed with epilepsy by a neurologist. The control group was selected from healthy individuals and matched to the case group. Serum zinc and copper were measured by the calorimetric method using a colorimetric method kit.Results:The mean zinc level was 60.1±22.6 ug/dl in the cases, and 102.1±18 ug/dl in the controls (p<0.001). The mean copper level was 180.1±32.4 ug/dl in cases compared with 114.5±18.5 ug/dl in controls (p<0.001).Conclusion:Serum zinc levels in epileptic children under drug treatment are lower compared with healthy children. Also, serum copper levels in these patients are significantly higher than in healthy people. No significant difference in the levels of serum copper and zinc was observed in using one drug or multiple drugs in the treatment of epileptic patients.

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Section: Discussionmentioning

confidence: 99%

Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants

Talat

Ahmed

Mohammed

2015

NSJ

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“…Significant increases of serum ChE (37,38) and CRP (39,40) have been reported in epileptic patients treated with different anticonvulsant drugs. In our patients having CRP concentrations lower than 10 mg/L (subclinical chronic inflammation), a significant positive correlation between serum ChE and CRP was found ( r = 0.410; P < 0.001); however, in the cases with CRP greater than 10 mg/L (acute inflammation conditions) the correlation coefficient between these two variables was negative, although due to the low number of patients considered, statistical significance was not achieved ( r = –0.405; P = 0.084).…”

Section: Discussionmentioning

confidence: 99%

A preliminary investigation on the possible association between diminished copper availability and non-alcoholic fatty liver disease in epileptic patients treated with valproic acid

Lampón

Tutor

2010

Upsala Journal of Medical Sciences

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BackgroundPatients treated with valproic acid (VPA) present a high incidence of non-alcoholic fatty liver disease (NAFLD) (around 61%). Several recent studies suggest that low copper stores could be associated with NAFLD, and a significant decrease of copper availability in VPA-treated patients has been described.Design and methodsIn 101 adult epileptic patients treated with valproic acid in monotherapy (n = 75) and polytherapy (n = 26) the copper availability was evaluated using the specific oxidase activity of ceruloplasmin (activity per unit mass of enzyme protein) and the copper/ceruloplasmin ratio. Copper deficiency was supposed in the cases in which this biochemical variable was smaller than the lower reference limit (333 U/g).ResultsThe differences between the groups of patients with ceruloplasmin oxidase activity smaller or greater than 333 U/g for the serum levels of aminotransferases, gamma-glutamyltransferase, butyrylcholinesterase, cholesterol, triglycerides, and C-reactive protein, and the APRI and FIB-4 liver fibrosis scores were not statistically significant. Most patients (93%) had low APRI and FIB-4 scores, suggesting absence of significant liver fibrosis.ConclusionsThe results obtained do not confirm the hypothesis of an association between diminished copper availability and NAFLD in patients treated with valproic acid.

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“…[137]). It is possible that induction of cholinesterase in epileptic patients treated with phenobarbital contributes to the changes in lipid levels [138]. Beneficial effects of phenobarbital on hyperbilirubinemia [139] and of phenobarbital and rifampicin on cholestasis [140] have been observed for decades.…”

Section: Experimental and Clinical Observationsmentioning

confidence: 99%

Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR

Handschin¹,

Meyer²

2005

Archives of Biochemistry and Biophysics

156

105

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Cloning and characterization of the orphan nuclear receptors constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2) led to major breakthroughs in studying drug-mediated transcriptional induction of drugmetabolizing cytochromes P450 (CYP). More recently, additional roles for CAR and PXR have been discovered. As examples, these xenosensors are involved in the homeostasis of cholesterol, bile acids, bilirubin and other endogenous hydrophobic molecules in the liver: CAR and PXR thus form an intricate regulatory network with other members of the nuclear receptor superfamily, foremost the cholesterol-sensing liver X receptor (LXR, NR1H2/3) and the bileacid-activated farnesoid X receptor (FXR, NR1H4). In this review, functional interactions between these nuclear receptors as well as the consequences on physiology and pathophysiology of the liver are discussed.Key Words: nuclear receptors; drug-induction; lipids; bile acids; cholesterol; CAR; PXR; LXR; FXR; cytochrome P450 -4 -Metabolism of drugs and other xenobiotics in the liver is our body's primary defense against accumulation of potentially toxic, lipophilic compounds. The superfamily of cytochromes P450 (CYPs) are the best-studied class of enzymes in this task [1]. Transcriptional and post-transcriptional regulation of CYPs after exposure to certain drugs or other xenobiotics has been described several decades ago. Classically, the barbiturate phenobarbital induces its own metabolism and excretion by elevating CYP levels [2]. However, the molecular mechanisms underlying this observation remained a conundrum until the discovery and subsequent characterization of the constitutive androstane receptor (CAR, official nomenclature NR1I3) and the pregnane X receptor (PXR, NR1I2, alternatively called PAR or SXR), two members of the superfamily of nuclear receptors [3][4][5][6][7]. Mice with genetic ablations of CAR and PXR have significantly reduced inducibility of CYPs by a variety of drugs [8,9]. Whereas these two receptors share some common ligands and also have an overlapping target gene pattern [10][11][12][13], the mode of activation for CAR and PXR is quite different [14]. PXR is located in the nucleus, it has a low basal activity and is highly activated upon ligand binding [14,15]. In contrast, in the non-induced state, CAR resides in the cytoplasm. After treatment with activators such as phenobarbital, CAR shuttles to the nucleus to activate its target genes. Moreover, CAR localization and activity is regulated by various protein phosphorylation events [16][17][18]. For a more detailed discussion of CAR and PXR functions in drug-mediated induction of CYPs, see some recent reviews (e.g. refs. [19-23] and references therein).-5 - The nuclear receptor NR1I group includes xenosensors and lipid-sensing membersCompounds that induce transcription of CYPs and that activate CAR and PXR are structurally very diverse [21]. However, most of them are small in size and are highly lipophilic [24]. Whereas the CAR ligand-binding domain stru...

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Possible Induction of Cholinesterase in Epileptic Patients Treated With Anticonvulsant Drugs: Relationship With Lipoprotein Levels

Cited by 6 publications

References 41 publications

Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants

Serum levels of zinc and copper in epileptic children during long-term therapy with anticonvulsants

A preliminary investigation on the possible association between diminished copper availability and non-alcoholic fatty liver disease in epileptic patients treated with valproic acid

Regulatory network of lipid-sensing nuclear receptors: roles for CAR, PXR, LXR, and FXR

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