Park Se Hwan, Ko Jeong Rim, Han Jin
Basic Research Laboratory, Department of Physiology, College of Medicine, Smart Marine Therapeutic Center, Cardiovascular and Metabolic Disease Core Research Support Center, Inje University, Busan 47392, Korea.
Department of Health Science and Technology, College of Medicine, Inje University, Busan 47392, Korea.
Korean J Physiol Pharmacol. 2024 Mar 1;28(2):145-152. doi: 10.4196/kjpp.2024.28.2.145.
Chemotherapy-induced cognitive impairment is recognized as the most typical symptom in patients with cancer that occurs during and following the chemotherapy treatment. Recently many studies focused on pharmaceutical strategies to control the chemotherapy side effects, however it is far from satisfactory. There may be a need for more effective treatment options. The aim of this study was to investigate the protective effect of exercise on cisplatin-induced neurotoxicity. Eightweek- old C57BL6 mice were separated into three group: normal control (CON, n = 8); cisplatin injection control (Cis-CON, n = 8); cisplatin with aerobic exercise (Cis-EXE, n = 8). Cisplatin was administered intraperitoneally at a dose of 3.5 mg/kg/day. The Cis-EXE group exercise by treadmill running (14-16 m/min for 45 min daily, 3 times/ week) for 12 weeks. Compared to the CON group, the cisplatin injection groups showed significant decrease in body weight and food intake, indicating successful induction of cisplatin toxicity. The Cis-CON group showed significantly increased levels of pro-inflammatory cytokines including IL-6, IL-1β, and TNF-α in the hippocampus, while the Cis-EXE group was significantly decreased in the expression of IL- 6, IL-1β, and TNF-α. In addition, compared to the CON group, the levels of synapserelated proteins including synapsin-1 and -2 were significantly reduced in the Cis- CON group, and there was a significant difference between the Cis-CON and Cis-EXE groups. Antioxidant and apoptosis factors were significantly improved in the Cis-EXE group compared with the Cis-CON group. This study suggest that exercise could be meaningful approach to prevent or improve cisplatin-induced cognitive impairment.
化疗引起的认知障碍被认为是癌症患者在化疗期间及化疗后出现的最典型症状。最近，许多研究聚焦于控制化疗副作用的药物策略，但效果远不尽人意。可能需要更有效的治疗选择。本研究的目的是探讨运动对顺铂诱导的神经毒性的保护作用。将8周龄的C57BL6小鼠分为三组：正常对照组（CON，n = 8）；顺铂注射对照组（Cis-CON，n = 8）；顺铂有氧运动组（Cis-EXE，n = 8）。以3.5 mg/kg/天的剂量腹腔注射顺铂。Cis-EXE组通过跑步机跑步进行运动（每天45分钟，速度为14 - 16米/分钟，每周3次），持续12周。与CON组相比，顺铂注射组的体重和食物摄入量显著下降，表明成功诱导了顺铂毒性。Cis-CON组海马中促炎细胞因子包括IL-6、IL-1β和TNF-α的水平显著升高，而Cis-EXE组IL-6、IL-1β和TNF-α的表达显著降低。此外，与CON组相比，Cis-CON组中包括突触素-1和-2在内的突触相关蛋白水平显著降低，且Cis-CON组和Cis-EXE组之间存在显著差异。与Cis-CON组相比，Cis-EXE组的抗氧化和凋亡因子显著改善。本研究表明，运动可能是预防或改善顺铂诱导的认知障碍的有效方法。
