期刊
BIOLOGICAL & PHARMACEUTICAL BULLETIN
卷 43, 期 2, 页码 348-355出版社
PHARMACEUTICAL SOC JAPAN
DOI: 10.1248/bpb.b19-00862
关键词
curcumin; oxaliplatin; peripheral neuropathic pain; nuclear factor-kappa B; oxidative stress; inflammation
资金
- National Natural Science Foundation of China [81302933]
- Science and Technology Commission Guidance Project of Shanghai [14401931300, 16401933700]
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-kappa B) 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 28d 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-kappa B and level of inflammatory factors like tumor necrosis factor-a (TNF-alpha), interleukin-1 beta (IL-1 beta) 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-kappa B and mitigating neuroinflammation.
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