Kim Sung Tae, Kyung Eun Jung, Suh Jung Sook, Lee Ho Sung, Lee Jun Ho, Chae Soo In, Park Eon Sub, Chung Yoon Hee, Bae Jinhyung, Lee Tae Jin, Lee Won Mo, Sohn Uy Dong, Jeong Ji Hoon
a Department of Pharmacology, College of Medicine , Chung-Ang University , Seoul , Republic of Korea.
c Department of Pharmacology, College of Pharmacy , Chung-Ang University , Seoul , Republic of Korea.
Drug Chem Toxicol. 2018 Oct;41(4):476-485. doi: 10.1080/01480545.2017.1390580. Epub 2017 Dec 6.
Docetaxel is a taxane chemotherapeutic agent used in the treatment of breast cancer, prostate cancer and gastric cancer, but several side effects such as peripheral neurotoxicity could occur. The present study was designed to investigate the therapeutic potential of phosphatidylcholine (PC) on docetaxel-induced peripheral neurotoxicity. Rats were randomly divided into three groups and treated for 4 weeks. Behavioral tests were conducted to measure the effects of PC on docetaxel-induced decreases in mechanical & thermal nociceptive threshold. Biochemical tests were conducted to measure the level of oxidative stress on sciatic nerve. Histopathological and immunohistochemical experiments were also conducted to assess neuronal damage and glial activation. PC treatment significantly attenuated docetaxel-induced changes in mechanical & thermal nociceptive response latencies. PC decreased oxidative stress in sciatic nerve by increasing antioxidant levels (glutathione, glutathione peroxidase and superoxide dismutase activity). In immunohistochemical evaluation, PC treatment ameliorated docetaxel-induced neuronal damage and microglial activation in the sciatic nerve and spinal cord. Thus, PC showed protective effects against docetaxel-induced peripheral neurotoxicity. These effects may be attributed to its antioxidant properties and modulation of microglia.
多西他赛是一种紫杉烷类化疗药物,用于治疗乳腺癌、前列腺癌和胃癌,但可能会出现一些副作用,如外周神经毒性。本研究旨在探讨磷脂酰胆碱(PC)对多西他赛诱导的外周神经毒性的治疗潜力。将大鼠随机分为三组并治疗4周。进行行为测试以测量PC对多西他赛诱导的机械性和热痛觉阈值降低的影响。进行生化测试以测量坐骨神经的氧化应激水平。还进行了组织病理学和免疫组织化学实验以评估神经元损伤和胶质细胞活化。PC治疗显著减轻了多西他赛诱导的机械性和热痛觉反应潜伏期的变化。PC通过提高抗氧化剂水平(谷胱甘肽、谷胱甘肽过氧化物酶和超氧化物歧化酶活性)降低了坐骨神经的氧化应激。在免疫组织化学评估中,PC治疗改善了多西他赛诱导的坐骨神经和脊髓中的神经元损伤和小胶质细胞活化。因此,PC对多西他赛诱导的外周神经毒性具有保护作用。这些作用可能归因于其抗氧化特性和对小胶质细胞的调节作用。