Τίτλος – Title
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Μεταβολές στη Δραστικότητα της Ακετυλχολινεστεράσης Εγκεφάλου Ενηλίκων Επιμύων μετά από Χορήγηση Θειοακεταμίδης ή/και Ελλιπούς σε Χολίνη Δίαιτας: ο Ρόλος του Οξειδωτικού Στρες και της In Vitro Επώασης με L-Καρνιτίνη Changes in the Activity of Adult Rat Brain Acetylcholinesterase after Administration of Thioacetamide and/or Choline-Deficient Diet: the Role of Oxidative Stress and of In Vitro Incubation with L-Carnitine |
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Συγγραφέας – Author
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Χ. Λιάπη1, Η. Al-Humadi1, Κ. Κοσμά2, Α. Ζάρρος1,3, Π. Γαλανοπούλου1, Β. Στολάκης3, Κ. Λιάτσος1, Ε. Γκρούζμαν1, Ζ. Μέλλιος3, Ν. Σκανδάλη1, Φ. Ανυφαντάκη1 , Σ. Τσακίρης3 1Εργαστήριο Φαρμακολογίας, 3Εργαστήριο Φυσιολογίας, Ιατρική Σχολή Εθνικού & Καποδιστριακού Πανεπιστημίου Αθηνών, Αθήνα, Ελλάς C. Liapi1, H. Al-Humadi1, K. Kosma2, A. Zarros1,3, P. Galanopoulou1, V. Stolakis3, K. Liatsos1, E. Gkrouzman1, Z. Mellios3, N. Skandali1, F. Anifantaki1, S. Tsakiris3 1Department of Pharmacology, 3Department of Physiology, Medical School, National & Kapodistrian University of Athens, Athens, Hellas |
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Παραπομπή – Citation
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Λιάπη,Χ., AlHumadi,Η., Κοσμά,Κ., Ζάρρος,Α., Γαλανοπούλου,Π., Στολάκης,Β., Λιάτσος,Κ., Γκρούζμαν,Ε., Μέλλιος,Ζ., Σκανδάλη,Ν., Ανυφαντάκη,Φ., Τσακίρης,Σ. : Μεταβολές στη Δραστικότητα της Ακετυλχολινεστεράσης Εγκεφάλου Ενηλίκων Επιμύων μετά από Χορήγηση Θειοακεταμίδης ή/και Ελλιπούς σε Χολίνη Δίαιτας: ο Ρόλος του Οξειδωτικού Στρες και της In Vitro Επώασης με L-Καρνιτίνη, Επιθεώρηση Κλιν. Φαρμακολ. Φαρμακοκινητ. 27: 40-41 (2009)
Liapi,C.,Al-Humadi,H., Kosma,K., Zarros,A., Galanopoulou,P., Stolakis,V., Liatsos,K., Gkrouzman,E., Mellios,Z., Skandali,N., Anifantaki,F., Tsakiris,S. : Changes in the Activity of Adult Rat Brain Acetylcholinesterase after Administration of Thioacetamide and/or Choline-Deficient Diet: the Role of Oxidative Stress and of In Vitro Incubation with L-Carnitine, Epitheorese Klin. Farmakol. Farmakokinet. 27: 40-41 (2009)
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Ημερομηνία Δημοσιευσης – Publication Date
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8 Μαρτίου 2009 – 2009-03-08
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Γλώσσα Πλήρους Κειμένου –
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Λέξεις κλειδιά – Keywords
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Εγκέφαλος επιμύων, έλλειψη χολίνης, θειοακεταμίδη, ακετυλχολινεστεράση, οξειδωτικό στρες, L-καρνιτίνη
Rat brain, choline-deficiency, thioacetamide, acetylcholinesterase, oxidative stress, L-carnitine
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Λοιποί Όροι – Other Terms
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Κλινική Μελέτη Clinical Trial |
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Περίληψη – Summary
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– Choline (Ch) is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions that affect the nervous system, while thioacetamide (TAA) is a well-known hepatotoxic agent. The induction of prolonged Ch-deprivation (CD) in rats receiving TAA (through the drinking water) provides an experimental model of mild progressive hepatotoxicity that could simulate commonly-presented cases in clinical practice. In this respect, the aim of this study was to investigate the effects of a 30-day dietary CD and/or TAA administration (300mg/L of drinking water) on the activity of brain acetylcholinesterase (AChE) in adult rats, as well as on the serum total antioxidant status (TAS). Μale Wistar rats were divided into four groups: A (control), B (CD), C (TAA), D (CD+TAA). Dietary CD was provoked through the administration of Ch-deficient diet. Rats were sacrificed by decapitation at the end of the 30-day experimental period and serum TAS, as well as whole brain AChE, were determined spectro-photometrically. Moreover, in vitro experiments were conducted in order to evaluate the potential neuroprotective role of L-carnitine (Carn, 5 mΜ) towards the combined toxicity of CD and TAA on the above crucial brain enzyme. Serum TAS was found significantly lowered by CD (-11%, p<0.01, BvsA) and CD+TAA (-19%, p<0.001, DvsA). The rat brain AChE activity was found significantly increased by TAA administration (+11%, p<0.01, CvsA), as well as by CD+TAA administration (+14%, p<0.01, DvsA). However, AChE was not found to be significantly altered by the 30-day dietary CD. The in vitro experiments showed that Carn cannot reverse the AChE activity increase. Further in vivo experiment are required in order to fully investigate the potential neuropretective role of Carn against the above-described (slight but significant) neurotoxic effect of CD and TAA coadministration on brain AChE activity. |
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Αναφορές – References
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1. Zeisel S.H.: Dietary choline: biochemistry, physiology, and pharmacology. Annu. Rev. Nutr. 1: 95-121 (1981)
2. Zeisel S.H.: Choline: an essential nutrient for humans. Nutrition 16: 669-671 (2000) 3. Fernández I., Fontana L., Gil A., Ríosc A., Torres M.I.: Dietary supplementation with monounsaturated and long-chain polyunsaturated fatty acids influences the liver structural recovery and hepatocyte binuclearity in female Wistar rats in experimental cirrhosis induced by thioacetamide. Exp. Toxicol. Pathol. 57: 65-75 (2005) 4. Pérez M.J., Sánchez-Medina F., Torres M., Gil A., Suárez A.: Dietary nucleotides enhance the liver redox state and protein synthesis in cirrhotic rats. J. Nutr. 134: 2504-2508 (2004) 5. Zarros A., Theocharis S., Skandali N., Tsakiris S.: Effects of fulminant hepatic encephalopathy on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase: comparison of the enzymes’ response to in vitro treatment with ammonia. Metab. Brain Dis. 23: 255-264 (2008) 6. Carageorgiou H., Tzotzes V., Pantos C., Mourouzis C., Zarros A., Tsakiris S.: In vivo and in vitro effects of cadmium on adult rat brain total antioxidant status, acetylcholinesterase, (Na+,K+)-ATPase and Mg2+-ATPase activities: protection by L-cysteine. Basic Clin. Pharmacol. Toxicol. 94: 112-118 (2004) 7. Lowry O.H., Rosebrough N.J., Farr A.L., Randall R.J.: Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193: 265-275 (1951) 8. Ellman G.L., Courtney K.D., Andres V.Jr., Featherstone R.M.: A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7: 88-95 (1961) 9. Virmani A., Gaetani F., Imam S., Binienda Z., Ali S.: Possible mechanism for the neuroprotective effects of L-carnitine on methamphetamine-evoked neurotoxicity. Ann. N. Y. Acad. Sci. 993: 197-207 (2003) 10. Schulpis K.H., Tsakiris S., Traeger-Synodinos J., Papassotiriou I.: Low total antioxidant status is implicated with high 8-hydroxy-2-deoxyguanosine serum concentrations in phenylketonuria. Clin. Biochem. 38: 239-242 (2005) 11. Liapi C., Feskou I., Zarros A., Galanopoulou P., Tsakiris S.: Effects of gestational and lactational choline deprivation on brain antioxidant status, acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase activities in offspring rats. Clin. Chem. Lab. Med. 45: 651-656 (2007) 12. Liapi C., Feskou I., Zarros A., Carageorgiou H., Galanopoulou P., Tsakiris S.: Equilibrated diet restores the effects of early age choline-deficient feeding on rat brain antioxidant status and enzyme activities: the role of homocysteine, L-phenylalanine and L-alanine. Metab. Brain Dis. 23: 289-301 (2008) |
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