乳香和莪术提取物通过调节 NF-κB 信号对奥沙利铂诱导的神经病变具有保护作用

Q1 Environmental Science Toxicology Reports Pub Date : 2024-10-20 DOI:10.1016/j.toxrep.2024.101781
Sakshi Mahajan , Varun Sureja , Dharmeshkumar Kheni , Vishal Dubey , Kiran Bhupathiraju , Venkata KrishnaRaju Alluri , Anuradha Majumdar
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引用次数: 0

摘要

奥沙利铂是第三代抗癌药,具有更好的疗效、更低的毒性和更广泛的抗肿瘤活性。使用奥沙利铂经常会引起慢性奥沙利铂诱导的神经病变(OIN),这是一种累积性现象,表现为感觉丧失、麻痹、感觉障碍和无法解决的本体感觉波动,极大地影响了患者的生活质量。由于 OIN 的不可避免性和高发病率,以及缺乏有效的预防药物,因此有必要开发有效可靠的保护方案,在保持抗癌活性的同时限制 OIN。慢性 OIN 的发病机制涉及神经炎症和氧化应激。本研究旨在探讨乳香和莪术通过调节核因子-kappa B(NF-κB)信号传导对神经的保护作用。通过行为测试来评估与长期服用奥沙利铂相关的冷异感、热痛、机械异感、机械痛和神经传导速度减慢。通过对坐骨神经匀浆中的炎性细胞因子进行定量分析,评估了 NF-κB 信号转导的调节和随后细胞因子的激活。其他评估包括氧化应激参数、血清神经元生物标志物和坐骨神经横截面检查。研究结果表明,50 毫克/千克和 75 毫克/千克剂量的乳香和莪术联合提取物可改善行为和生化参数以及神经组织学。因此,本研究证明了乳香和莪术联合提取物通过调节 NF-κB 信号传导对 OIN 的保护潜力。
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Protective effects of Boswellia and Curcuma extract on oxaliplatin-induced neuropathy via modulation of NF-κB signaling
Oxaliplatin is a third-generation anticancer agent with better efficacy, lower toxicity, and a broad spectrum of antineoplastic activity. Its use is frequently associated with chronic oxaliplatin-induced neuropathy (OIN), a cumulative phenomenon manifesting as loss of sensation, paresthesia, dysesthesia, and irresolvable fluctuations in proprioception that greatly affect the patients’ quality of life. The inevitable nature and high incidence of OIN, along with the absence of efficacious preventive agents, necessitate the development of effective and reliable protective options for limiting OIN while maintaining anticancer activity. The pathogenesis of chronic OIN involves neuroinflammation and oxidative stress. This study aimed to explore the neuroprotective effects of Boswellia serrata and Curcuma longa via modulation of nuclear factor-kappa B (NF-κB) signaling. Behavioral tests were conducted to assess cold allodynia, heat hyperalgesia, mechanical allodynia, mechanical hyperalgesia, and slowed nerve conduction velocity associated with chronic oxaliplatin administration. The modulation of NF-κB signaling and the subsequent activation of cytokines were evaluated through quantitative analysis of inflammatory cytokines in sciatic nerve homogenates. Additional assessments included oxidative stress parameters, serum neuronal biomarkers, and examination of sciatic nerve cross-sections. The findings indicate improvements in behavioral and biochemical parameters, as well as nerve histology, with the combined extract of Boswellia serrata and Curcuma longa at doses of 50 mg/kg and 75 mg/kg. Thus, this study presents evidence for the protective potential of the combined extract of Boswellia serrata and Curcuma longa in OIN through modulation of NF-κB signaling.
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来源期刊
Toxicology Reports
Toxicology Reports Environmental Science-Health, Toxicology and Mutagenesis
CiteScore
7.60
自引率
0.00%
发文量
228
审稿时长
11 weeks
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