Department of Traditional Chinese Medicine, Changzheng Hospital, Second Military Medical University.
Department of Respiration, Changhai Hospital, Second Military Medical University.
Biol Pharm Bull. 2020 Feb 1;43(2):348-355. doi: 10.1248/bpb.b19-00862. Epub 2019 Nov 26.
Oxaliplatin is a first-line clinical drug in cancer treatment and its side effects of peripheral neuropathic pain have also attracted much attention. Neuroinflammation induced by oxidative stress-mediated activation of nuclear factor-kappa B (NF-κB) plays an important role in the course. Current studies have shown that curcumin has various biological activities like antioxidant, anti-inflammatory, antitumor and so on, while few studies were conducted about its role in oxaliplatin-induced peripheral neuropathic pain. The aim of this study is to verify the mechanism of curcumin alleviating oxaliplatin-induced peripheral neuropathic pain. Intraperitoneal injection with oxaliplatin (4 mg/kg body weight) was given to the rats twice a week and last for four weeks to establish the model rats. Gavage administration of curcumin (12.5, 25, and 50 mg/kg body weight, respectively) was conducted for consecutive 28 d to explore the effects and potential mechanism. Our results showed that curcumin administration could increase mechanical withdrawal threshold and decrease the paw-withdrawal times of cold allodynia significantly; meanwhile, motor nerve conduction velocity (MNCV) and sense nerve conduction velocity (SNCV) were both increased and the injured neurons of the spinal cord were repaired. In addition, curcumin administration increased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and reduced malondialdehyde (MDA). Moreover, the curcumin operation inhibited the activated of NF-κB and level of inflammatory factors like tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). In conclusion, these findings suggested that curcumin could alleviate oxaliplatin-induced peripheral neuropathic pain; the mechanism might be inhibiting oxidative stress-mediated activation of NF-κB and mitigating neuroinflammation.
奥沙利铂是癌症治疗的一线临床药物，其周围神经病理性疼痛的副作用也引起了广泛关注。氧化应激介导的核因子-κB（NF-κB）激活引起的神经炎症在发病过程中起重要作用。目前的研究表明，姜黄素具有抗氧化、抗炎、抗肿瘤等多种生物学活性，而关于其在奥沙利铂诱导的周围神经病理性疼痛中的作用的研究较少。本研究旨在验证姜黄素缓解奥沙利铂诱导的周围神经病理性疼痛的机制。腹腔注射奥沙利铂（4mg/kg 体重），每周两次，持续四周，建立模型大鼠。连续 28 天给予姜黄素（分别为 12.5、25 和 50mg/kg 体重）灌胃给药，探讨其作用及潜在机制。结果表明，姜黄素给药可显著提高机械性缩足阈值，减少冷感觉异常的足底退缩次数；同时，运动神经传导速度（MNCV）和感觉神经传导速度（SNCV）均升高，脊髓损伤神经元得到修复。此外，姜黄素给药可增加超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、过氧化氢酶（CAT）活性，降低丙二醛（MDA）含量。此外，姜黄素可抑制 NF-κB 的激活及肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）等炎症因子的水平。综上所述，这些发现表明姜黄素可缓解奥沙利铂诱导的周围神经病理性疼痛，其机制可能是抑制氧化应激介导的 NF-κB 激活，减轻神经炎症。
