Laboratório de Tecnologia Farmacêutica, Programa de Pós-graduação em Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde, Porto Alegre, RS, Brazil.
J Trace Elem Med Biol. 2019 Sep;55:180-189. doi: 10.1016/j.jtemb.2019.06.010. Epub 2019 Jul 5.
Gliomas are the most aggressive malignant tumors of the central nervous system. The diphenyl diselenide [(PhSe)] is an organoselenium compound that has multiple pharmacological properties. Previous reports showed that (PhSe) nanoencapsulation potentiates its in vitro antitumoral action and reduces its toxicity.
In this sense, the current study was designed to further evaluate the (PhSe) antitumoral effect by a set of in vitro techniques using a glioma cell line as well as by an animal model of gliobastoma.
For the in vitro tests, the cell viability, propidium iodide uptake and nitrite levels of rat glioma C6 cells were determined after incubation with free (PhSe) or (PhSe)-loaded nanocapsules (NC). The glioblastoma model was induced by implantation of C6 glioma cells in the right striatum of rats. Following, animals were submitted to a repeated intragastric administration treatment with (PhSe) or NC (PhSe) (1 mg/kg/day for 15 days) to assess the possible antitumor effect.
Both compound forms decreased the C6 glioma cells viability without causing any effect in astrocytes cells (healthy control). Importantly, the NC (PhSe) had superior cytotoxic effect than its free form and increased the nitrite content. Independent of the (PhSe) forms, the intragastric treatment reduced brain tumor size and caused neither alteration in the plasma renal and hepatic markers of function nor in the parameters of oxidative balance in brain, liver and kidneys.
The (PhSe) nanoencapsulation improved its cytotoxic effect against C6 glioma cells and both compound forms attenuated the tumor development.
神经胶质瘤是中枢神经系统最具侵袭性的恶性肿瘤。二苯基二硒醚[(PhSe)]是一种具有多种药理特性的有机硒化合物。先前的报告表明,(PhSe)纳米囊化增强了其体外抗肿瘤作用,并降低了其毒性。
从这个意义上说,本研究旨在进一步通过一组体外技术评估(PhSe)的抗肿瘤作用,该技术使用神经胶质瘤细胞系和神经胶质瘤动物模型进行。
在体外试验中,用游离(PhSe)或(PhSe)负载纳米胶囊(NC)孵育大鼠神经胶质瘤 C6 细胞后,测定细胞活力、碘化丙啶摄取和亚硝酸盐水平。采用 C6 神经胶质瘤细胞植入大鼠右侧纹状体诱导神经胶质瘤模型。随后,动物接受重复灌胃给予(PhSe)或 NC(PhSe)(1mg/kg/天,共 15 天)治疗,以评估可能的抗肿瘤作用。
两种化合物形式均降低了 C6 神经胶质瘤细胞的活力,但对星形胶质细胞(健康对照)没有任何影响。重要的是,NC(PhSe)的细胞毒性作用优于游离形式,并增加了亚硝酸盐含量。无论(PhSe)的形式如何,灌胃治疗均降低了脑肿瘤的大小,并且不会改变血浆肾和肝功能标志物,也不会改变脑、肝和肾的氧化平衡参数。
(PhSe)纳米囊化提高了其对 C6 神经胶质瘤细胞的细胞毒性作用,两种化合物形式均减轻了肿瘤的发展。