The Journal of Membrane Biology ( IF 2.3 ) Pub Date : 2021-02-18 , DOI: 10.1007/s00232-021-00173-2 Gabriela Machado Parreira 1 , Jéssica Alves Faria 2 , Sarah Melo Silva Marques 1 , Israel José Pereira Garcia 1 , Isabella Ferreira Silva 3 , Luciana Estefani Drumond De Carvalho 1 , José Augusto Ferreira Perez Villar 4 , Matthews Vieira Machado 4 , Maira de Castro Lima 2 , Leandro Augusto Barbosa 1 , Vanessa Faria Cortes 1 , Hérica de Lima Santos 1
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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
中文翻译：
γ-亚苄基地高辛衍生物 BD-15 增加大鼠海马和前额叶皮层的 α3-Na、K-ATP 酶活性，对心脏无变化
我们的研究旨在研究新型强心类固醇 BD-15（γ-亚苄基衍生物）对大鼠海马、前额叶皮层和心脏的行为参数、氧化应激和 Na、K-ATP 酶活性的影响，以验证其安全性。并可能用于脑部疾病。对于这项研究，在腹腔注射 20、100 和 200 µg/Kg 的 BD-15 后，使用了几组雄性 Wistar 大鼠。各组连续治疗三天，对照组接受0.9%生理盐水。BD-15 没有改变用不同剂量治疗的大鼠的行为。对于在海马中测试的所有剂量的 BD-15，观察到特定 α2,3-Na, K-ATPase 活性的增加。然而，在前额叶皮层中，仅 100 µg/Kg 的剂量增加了所有 Na、K-ATPase 异构体的活性。BD-15 不会引起海马中脂质过氧化水平的改变，但在前额叶皮质中，观察到脂质过氧化水平降低（~25%）。在海马中，GSH 水平随着所有测试剂量的增加而增加，而在前额叶皮层中没有发现变化。随后，当分析 BD-15 对心脏组织的影响时，在测试参数中没有观察到变化。100 µg/Kg 剂量的 BD-15 被证明是有希望的，因为它被认为可以治疗脑部疾病，因为它可以增加海马和前额叶皮层中 α3-Na、K-ATP 酶的活性，并降低这些大脑区域的氧化应激。此外，这种药物不会引起心脏和肾脏组织的变化，优先表现出对大脑的特异性。
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