Department of Pharmacology, College of Pharmacy, Chung-Ang University, Seoul, 156-756, Republic of Korea.
Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 156-756, Republic of Korea.
Life Sci. 2015 Jun 1;130:81-7. doi: 10.1016/j.lfs.2015.03.013. Epub 2015 Mar 25.
The present study was designed to investigate the therapeutic potential of phosphatidylcholine (PC) on oxaliplatin-induced peripheral neuropathy.
Male Sprague-Dawley rats were randomly divided into three groups: the control group, the oxaliplatin group (4mg/kg, twice per week for 4weeks) and the oxaliplatin+PC (300mg/kg) group. To evaluate the effect of PC, we examined the thermal nociceptive threshold changes in oxaliplatin-induced peripheral neuropathy by conducting paw pressure, hot-plate and tail-flick tests. Additional experiments on the degree of oxidative stress in the sciatic nerves were performed by measuring the level of MDA, total glutathione (GSH), glutathione peroxidase (GPx) activity and superoxide dismutase (SOD) activity. We also used histopathological and immunohistochemical methods to observe neuronal damage and glial activation.
PC attenuated oxidative stress by increasing antioxidant levels. In histopathological evaluation, the PC administrated group maintained normal morphologic appearance of sciatic nerves, similar to the control group. In spinal cords, however, no significant difference between the oxaliplatin-alone group and the oxaliplatin+PC group was observed. In the immunohistochemical evaluation, PC administration ameliorated oxaliplatin-induced microglial activation.
It is suggested that PC has a therapeutic potential against oxaliplatin-induced peripheral neuropathy due to its antioxidant property and modulation of microglial activities.
本研究旨在探讨磷脂酰胆碱(PC)对奥沙利铂诱导的周围神经病变的治疗潜力。
雄性 Sprague-Dawley 大鼠随机分为三组:对照组、奥沙利铂组(4mg/kg,每周两次,共 4 周)和奥沙利铂+PC 组(300mg/kg)。为了评估 PC 的效果,我们通过足底压力、热板和尾巴闪烁测试来检测奥沙利铂诱导的周围神经病变中热痛觉阈值的变化。通过测量丙二醛(MDA)、总谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GPx)活性和超氧化物歧化酶(SOD)活性,进一步研究坐骨神经中氧化应激的程度。我们还使用组织病理学和免疫组织化学方法观察神经元损伤和神经胶质细胞激活。
PC 通过增加抗氧化剂水平来减轻氧化应激。在组织病理学评估中,PC 给药组维持了坐骨神经的正常形态,与对照组相似。然而,在脊髓中,奥沙利铂单独组和奥沙利铂+PC 组之间没有观察到显著差异。在免疫组织化学评估中,PC 给药减轻了奥沙利铂诱导的小胶质细胞激活。
由于具有抗氧化特性和调节小胶质细胞活性,PC 对奥沙利铂诱导的周围神经病变具有治疗潜力。