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Disubstituted diaryl diselenides inhibit δ-ALA-D and Na+, K+-ATPase activities in rat brain homogenates in vitro

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Abstract

Toxicological and pharmacological studies demonstrated that the introduction of functional groups into the aromatic ring of diphenyl diselenide alter its effect. The aim of this study was to evaluate the in vitro effect of m-trifluoromethyl-diphenyl diselenide (m-CF3–C6H4Se)2, p-chloro-diphenyl diselenide (p-Cl–C6H4Se)2 and p-methoxyl-diphenyl diselenide (p-CH3O–C6H4Se)2 on δ-aminolevulinate dehydratase (δ-ALA-D) and Na+, K+-ATPase activities in rat brain homogenates. Diselenides inhibited δ-ALA-D activity (IC50 4–6 μM [concentration inhibiting 50%]), and dithiothreitol (DTT) restored the enzyme activity. ZnCl2 (100 μM) did not restore δ-ALA-D inhibition caused by (p-Cl–C6H4Se)2 and (m-CF3–C6H4Se)2. Na+, K+-ATPase activity was more sensitive to (p-Cl–C6H4Se)2 and (m-CF3–C6H4Se)2 (IC50 6 μM) than (p-CH3O–C6H4Se)2 and (PhSe)2 (IC50 45 and 31 μM, respectively). DTT restored the activity of Na+, K+-ATPase inhibited by diselenides. The effect of diselenides on Na+/K+-ATPase is dependent on their substitutions in the aromatic ring. The mechanism through which diselenides inhibit δ-ALA-D and Na+, K+-ATPase activities involves the oxidation of thiol groups.

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Acknowledgments

The financial support by Universidade Federal de Santa Maria (UFSM), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) is gratefully acknowledged. C.A.B, C·W.N and G.Z. are recipients of CNPq fellowships.

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  1. Departamento de Química, Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil

    César Augusto Brüning, Marina Prigol, Daniela A. Barancelli, Cristina Wayne Nogueira & Gilson Zeni

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  1. César Augusto Brüning
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  2. Marina Prigol
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Correspondence to Gilson Zeni.

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Brüning, C.A., Prigol, M., Barancelli, D.A. et al. Disubstituted diaryl diselenides inhibit δ-ALA-D and Na+, K+-ATPase activities in rat brain homogenates in vitro. Mol Cell Biochem 332, 17–24 (2009). https://doi.org/10.1007/s11010-009-0169-3

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