Teratogenic and anticonvulsant effects of zinc and copper valproate complexes in zebrafish.

Autor: Grünspan LD; LBIOP - Laboratory of Biotechnology of Natural and Synthetics Products, Technology Department, Biotechnology Institute, University of Caxias do Sul, Caxias do Sul, Brazil., Mussulini BHM; Laboratory of Cellular Neurochemistry - Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Biológicas - Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Porto Alegre, RS, Brazil., Baggio S; Laboratory of Cellular Neurochemistry - Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Biológicas - Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Porto Alegre, RS, Brazil., Dos Santos PR; LBIOP - Laboratory of Biotechnology of Natural and Synthetics Products, Technology Department, Biotechnology Institute, University of Caxias do Sul, Caxias do Sul, Brazil., Dumas F; Laboratoire BioCIS, UMR CNRS 8076, Chimie des SubstancesNaturelles, IPSIT, Université Paris-Saclay, Université Paris-Sud, Faculté de Pharmacie, 5, rue Jean-Baptiste Clément, 92296, Châtenay-Malabry, France., Rico EP; Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense UNESC, Av. Universitária, 1105, Bairro Universitário, 88806-000 Criciúma, SC, Brazil., de Oliveira DL; Laboratory of Cellular Neurochemistry - Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Ciências Biológicas - Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Porto Alegre, RS, Brazil., Moura S; LBIOP - Laboratory of Biotechnology of Natural and Synthetics Products, Technology Department, Biotechnology Institute, University of Caxias do Sul, Caxias do Sul, Brazil. Electronic address: sidnei.moura@ucs.br.
Jazyk: angličtina
Zdroj: Epilepsy research [Epilepsy Res] 2018 Jan; Vol. 139, pp. 171-179. Date of Electronic Publication: 2018 Jan 19.
DOI: 10.1016/j.eplepsyres.2018.01.005
Abstrakt: Valproic acid (VPA) is an antiepileptic drug (AED) that has the broadest spectrum across all types of seizures and epileptic syndromes. Unfortunately, approximately 30% of epileptic patients are refractory to the classical AED. Metal ions have been frequently incorporated into pharmaceuticals for therapeutic or diagnostic purposes and research. In this preliminary study, we assess the embryo toxicity and the anticonvulsant activity of 4 novel metallodrugs, with Zn +2 and Cu +2 , a derivative of valproic acid and the N-donor ligand in an adult zebrafish epileptic seizure model induced by pentylenetetrazole. The most toxic complex was [Cu(Valp) 2 Bipy], in which the LC 50 was 0.22 μM at 48 h post fertilization (HPF) and 0.12 μM at 96 HPF, followed by [Zn(Valp) 2 Bipy] (LC 50  = 10 μM). These same metallodrugs ([Cu(Valp) 2 Bipy] 10 mM/kg and [Zn(Valp) 2 Bipy] 30 mM and 100 mM/kg) displayed superior activity, thus reducing the seizure intensity by approximately 20 times compared to sodium valproate (175 mM/kg). Overall, [Cu(Valp) 2 Bipy] showed the best anticonvulsant effects. However, because of the toxicity of copper, [Zn(Valp) 2 Bipy] is considered the most promising anticonvulsant for future studies.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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