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

• Published in: The Journal of membrane biology 2021-04, Vol.254 (2), p.189-199
• Main Authors: Parreira, Gabriela Machado, Faria, Jéssica Alves, Marques, Sarah Melo Silva, Garcia, Israel José Pereira, Silva, Isabella Ferreira, De Carvalho, Luciana Estefani Drumond, Villar, José Augusto Ferreira Perez, Machado, Matthews Vieira, de Castro Lima, Maira, Barbosa, Leandro Augusto, Cortes, Vanessa Faria, de Lima Santos, Hérica
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Brain; Digoxin; Disorders; Dosage; Heart; Hippocampus; Human Physiology; Isoforms; Kidneys; Life Sciences; Lipid peroxidation; Lipids; Na+/K+-exchanging ATPase; Oxidative stress; Parameters; Prefrontal cortex; Steroids
• ISSN: 0022-2631; 1432-1424
• DOI: 10.1007/s00232-021-00173-2

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. Graphic Abstract