Guzman David C, Bratoeff Eugene, Ortiz Aylin S, Garcia Ernestina H, Brizuela Norma O, Mejia Gerardo B, Olguin Hugo J, del Angel Daniel S, Cruz Israel M
Laboratorio de Farmacología, Instituto Nacional de Pediatría, Av Iman Nun 1, 3 er piso, Col Cuicuilco, CP 04530, Mexico City, Mexico.
Endocr Metab Immune Disord Drug Targets. 2014;14(2):126-33. doi: 10.2174/1871530314666140331102306.
Flutamide is a drug used in the treatment of androgen-dependent disorders. However, this treatment is usually accompanied by some adverse side effects. The aim of this work was to analyse the effect of flutamide and to compare this effect with that of a synthetic steroid - 3β-propionyloxy-5-androsten-17-one (PPA) - on levels of dopamine and some oxidative stress markers. For this, thirty-six male young Wistar rats (65g) were recruited and divided into 6 groups. The groups were then treated as follows: Group 1 (control), dimethyl sulfoxide (DMSO); group 2, flutamide (4 mg/kg); group 3, PPA; group 4, DMSO + fructose; group 5, flutamide + fructose; and group 6, PPA + fructose. The treatments were administered intraperitoneally at a daily dose of 4 mg/kg for 10 days. In the last day of treatment, blood samples were obtained and used to assess the levels of glucose and cholesterol. The animals were then sacrificed and their prostate gland and brains were obtained for measurement of 5α-reductase, glutathione (GSH), calcium, H2O2, and dopamine in cortex, hemispheres, and medulla/oblongata, using previously validated methods.
Dopamine levels decreased while GSH increased significantly in cortex and hemispheres of animals that received PPA plus fructose. Also in the same group, GSH decreased in cerebellum/medulla oblongata when compared with control group. Peroxidation decreased significantly in all tissues of the groups, while ATPase activity witnessed a significant decrease in cortex and an increase in hemispheres of animal groups treated with flutamide and PPA both in combination with fructose.
The steroid, 3β-propionyloxy-5-androsten-17-one, may in part act as a neuroprotector mediated by the increase of GSH and decrease of H2O2. Besides, imbalance in steroid homeostasis may alter the metabolism of dopamine.
氟他胺是一种用于治疗雄激素依赖性疾病的药物。然而，这种治疗通常伴随着一些不良副作用。这项工作的目的是分析氟他胺的作用，并将其与合成类固醇3β-丙酰氧基-5-雄烯-17-酮（PPA）对多巴胺水平和一些氧化应激标志物的作用进行比较。为此，招募了36只雄性幼年Wistar大鼠（65克）并将其分为6组。然后对这些组进行如下处理：第1组（对照组），二甲亚砜（DMSO）；第2组，氟他胺（4毫克/千克）；第3组，PPA；第4组，DMSO +果糖；第5组，氟他胺+果糖；第6组，PPA +果糖。以每日剂量4毫克/千克腹腔注射给药，持续10天。在治疗的最后一天，采集血样并用于评估葡萄糖和胆固醇水平。然后处死动物，获取其前列腺和大脑，使用先前验证的方法测量皮质、半球和延髓/延髓中5α-还原酶、谷胱甘肽（GSH）、钙、H2O2和多巴胺的水平。
接受PPA加果糖的动物的皮质和半球中多巴胺水平降低，而GSH显著增加。同样在同一组中，与对照组相比，小脑/延髓中的GSH降低。各组所有组织中的过氧化作用均显著降低，而在同时接受氟他胺和PPA并与果糖联合治疗的动物组中，ATP酶活性在皮质中显著降低，在半球中增加。
类固醇3β-丙酰氧基-5-雄烯-17-酮可能部分作为一种神经保护剂，通过GSH的增加和H2O2的减少介导。此外，类固醇稳态失衡可能会改变多巴胺的代谢。
