Department of Human Physiology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Delta State, Nigeria.
Department of Basic Medical Science, Achievers University, Owo, Ondo State, Nigeria.
Naunyn Schmiedebergs Arch Pharmacol. 2021 Apr;394(4):717-734. doi: 10.1007/s00210-020-02003-z. Epub 2020 Nov 4.
Over the years, mounting evidences have suggested a strong association between chronic chlorpromazine therapy, a popular first-generation antipsychotic drug, and psycho-neuroendocrine changes. In this study, we aim to examine whether treatment with taurine and coenzyme Q10 (COQ-10), compounds with steroidogenic-gonadotropin hormone-enhancing properties, can attenuate the negative impacts of chlorpromazine on steroidogenic, gonadotropin, thyroid and HPA-axis hormones, dopamine levels, catalepsy behavior and neuronal cells of the hypothalamus and pituitary gland in the preventive and reversal treatments in male Wister rats. In the drug treatment alone or preventive protocol, rats received oral administration of saline (10 mL/kg), taurine (150 mg/kg/day), COQ-10 (10 mg/kg/day), or both (taurine + COQ-10/day) alone for 56 consecutive days, or in combination with oral chlorpromazine (30 mg/kg/day) treatment from days 29 to 56. In the reversal protocol, the animals received chlorpromazine or saline for 56 days prior to taurine, COQ-10, or the combination from days 29 to 56. Thereafter, serum prolactin, steroidogenic (testosterone, estrogen, progesterone), gonadotropin (luteinizing hormone, LH, follicle-stimulating hormone, FSH), thyroid (thyrotropin-stimulating hormone, tetraiodothyronine, triiodothyronine) hormones, corticosterone, brain dopamine levels and cataleptic behavior were investigated. The histopathological features of the hypothalamus and pituitary gland were also evaluated. Taurine, COQ-10, or their combination prevented and reversed chlorpromazine-induced hyperprolactinemia, decrease in FSH, LH, testosterone, progesterone and dopamine concentrations, as well as the increase in estrogen levels. Taurine and COQ-10 reduced the changes in thyroid hormones, corticosterone release, histological distortions of the hypothalamus and the pituitary gland of chlorpromazine-treated rats. Taurine and COQ-10 attenuated chlorpromazine-induced catalepsy. The study showed that taurine and COQ-10 prevented and reversed chlorpromazine-induced changes in reproductive, thyroid hormones, dopamine level, corticosterone release, neurodegenerations, and cataleptic behavior in rats.
多年来，越来越多的证据表明，慢性氯丙嗪治疗（一种流行的第一代抗精神病药物）与神经精神内分泌变化之间存在密切关联。在这项研究中，我们旨在研究牛磺酸和辅酶 Q10（COQ-10）的治疗是否可以减轻氯丙嗪对雄性 Wistar 大鼠下丘脑和垂体的甾体生成、促性腺激素、甲状腺和 HPA 轴激素、多巴胺水平、僵住行为和神经元细胞的负面影响，这两种化合物具有增强甾体生成促性腺激素的特性。在单独药物治疗或预防方案中，大鼠连续 56 天接受口服生理盐水（10 mL/kg）、牛磺酸（150 mg/kg/天）、COQ-10（10 mg/kg/天）或两者（牛磺酸+COQ-10/天），或从第 29 天到第 56 天与口服氯丙嗪（30 mg/kg/天）联合治疗。在逆转方案中，动物在第 29 天至第 56 天接受氯丙嗪或生理盐水治疗 56 天后，接受牛磺酸、COQ-10 或两者联合治疗。此后，研究了血清催乳素、甾体生成（睾酮、雌激素、孕酮）、促性腺激素（促黄体生成素、LH、促卵泡激素、FSH）、甲状腺（促甲状腺激素刺激素、四碘甲状腺原氨酸、三碘甲状腺原氨酸）激素、皮质酮、脑多巴胺水平和僵住行为。还评估了下丘脑和垂体的组织病理学特征。牛磺酸、COQ-10 或两者的联合预防和逆转了氯丙嗪引起的高催乳素血症、FSH、LH、睾酮、孕酮和多巴胺浓度降低，以及雌激素水平升高。牛磺酸和 COQ-10 减少了甲状腺激素、皮质酮释放、氯丙嗪治疗大鼠下丘脑和垂体的组织扭曲的变化。牛磺酸和 COQ-10 减轻了氯丙嗪引起的僵住行为。该研究表明，牛磺酸和 COQ-10 预防和逆转了氯丙嗪引起的大鼠生殖、甲状腺激素、多巴胺水平、皮质酮释放、神经退行性变和僵住行为的变化。
