The γ-Benzylidene Digoxin Derivative BD-15 Increases the α3-Na, K-ATPase Activity in Rat Hippocampus and Prefrontal Cortex and no Change on Heart

Abstract

Our study aimed to investigate the effects of the new cardiotonic steroid BD-15 (γ-benzylidene derivatives) in the behavioral parameters, oxidative stress and the Na, K-ATPase activity in the hippocampus, prefrontal cortex and heart from rats to verify the safety and possible utilization in brain disorders. For this study, groups of male Wistar rats were used after intraperitoneal injection of 20, 100 and 200 µg/Kg with BD-15. The groups were treated for three consecutive days and the control group received 0.9% saline. BD-15 did not alter behavior of rats treated with different doses. An increase in the specific α2,3-Na, K-ATPase activity was observed for all doses of BD-15 tested in the hippocampus. However, in the prefrontal cortex, only the dose of 100 µg/Kg increased the activity of all Na, K-ATPase isoforms. BD-15 did not cause alteration in the lipid peroxidation levels in the hippocampus, but in the prefrontal cortex, a decrease of lipid peroxidation (~ 25%) was observed. In the hippocampus, GSH levels increased with all doses tested, while in the prefrontal cortex no changes were found. Subsequently, when the effect of BD-15 on cardiac tissue was analyzed, no changes were observed in the tested parameters. BD-15 at a dosage of 100 µg/Kg proved to be promising because it is considered therapeutic for brain disorders, since it increases the activity of the α3-Na, K-ATPase in the hippocampus and prefrontal cortex, as well as decreasing the oxidative stress in these brain regions. In addition, this drug did not cause changes in the tissues of the heart and kidneys, preferentially demonstrating specificity for the brain.

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Acknowledgements

This study was partially funded by the FAPEMIG (Fundação de Amparo a Pesquisa do Estado de Minas Gerais) APQ-00290-16, APQ-00855-19 and CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) 401914/2016-0. We are grateful to Maria das Graças Carvalho for his contribution in correcting English. We would like to thank Dr. Hélio Batista dos Santos and Ralph Gruppi Thomé for their assistance in the histology experiments.

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Parreira, G.M., Faria, J.A., Marques, S.M.S. et al. The γ-Benzylidene Digoxin Derivative BD-15 Increases the α3-Na, K-ATPase Activity in Rat Hippocampus and Prefrontal Cortex and no Change on Heart. J Membrane Biol (2021). https://doi.org/10.1007/s00232-021-00173-2

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Keywords

  • Cardiotonic steroids
  • Na, K-ATPase
  • Oxidative stress
  • Hippocampus
  • Prefrontal cortex
  • Heart