Abdelkader Noha F, Saad Muhammed A, Abdelsalam Rania M
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
J Neurochem. 2017 May;141(3):449-460. doi: 10.1111/jnc.13978. Epub 2017 Mar 21.
One-third of cancer patients undergoing chemotherapy treatment often display symptoms of depression leading to poor adherence and decreased quality of life. Thus, this study aimed to investigate the possible protective effect of nebivolol against cisplatin-associated depressive symptoms in adult male rats. Nebivolol is a highly cardioselective β-adrenergic receptor blocker that possesses endothelium-dependent vasodilator properties and antioxidant capacities. Animals were allocated into four groups. Group one was given aqueous solution of carboxymethyl cellulose and served as control, group two was given nebivolol (10 mg/kg p.o., daily), group three was given cisplatin (2 mg/kg i.p. once per week) for 10 consecutive weeks and group four was treated with cisplatin concomitantly with nebivolol as per above schedule. Cisplatin-treated rats showed an increase in both depressive-like behaviors in open-field and forced swimming tests. In addition, histopathological examination revealed cortical encephalomalacia along with hippocampal neuronal degeneration and kidney dysfunction. In parallel, cisplatin administration prominently reduced GABA and elevated glutamate levels in the cortical and hippocampal tissues. Furthermore, it resulted in a significant decline in cortical and hippocampal brain-derived neurotrophic factor and nitric oxide contents concomitantly with a marked decrease in endothelial- and an increase in inducible-nitric oxide synthase genes expression. On the other hand, treatment with nebivolol effectively mitigated the aforementioned cisplatin-associated behavioral, biochemical, and histopathological alterations without changing its antitumor activity as evidenced by sulforhodamine B cell survival assay. Taken together, our results suggest that nebivolol may offer a promising approach for alleviating depressive symptoms associated with the use of cisplatin.
接受化疗的癌症患者中有三分之一经常表现出抑郁症状，导致依从性差和生活质量下降。因此，本研究旨在探讨奈必洛尔对成年雄性大鼠顺铂相关抑郁症状的可能保护作用。奈必洛尔是一种高度心脏选择性β-肾上腺素能受体阻滞剂，具有内皮依赖性血管舒张特性和抗氧化能力。将动物分为四组。第一组给予羧甲基纤维素水溶液作为对照，第二组给予奈必洛尔（10毫克/千克口服，每日），第三组连续10周每周一次腹腔注射顺铂（2毫克/千克），第四组按照上述方案同时给予顺铂和奈必洛尔治疗。顺铂处理的大鼠在旷场试验和强迫游泳试验中的抑郁样行为均增加。此外，组织病理学检查显示皮质脑软化以及海马神经元变性和肾功能障碍。同时，顺铂给药显著降低了皮质和海马组织中的γ-氨基丁酸水平并升高了谷氨酸水平。此外，它导致皮质和海马脑源性神经营养因子和一氧化氮含量显著下降，同时内皮型一氧化氮合酶基因表达显著降低，诱导型一氧化氮合酶基因表达增加。另一方面，如磺基罗丹明B细胞存活试验所示，奈必洛尔治疗有效地减轻了上述与顺铂相关的行为、生化和组织病理学改变，而不改变其抗肿瘤活性。综上所述，我们的结果表明奈必洛尔可能为减轻与顺铂使用相关的抑郁症状提供一种有前景的方法。
