Pan Tianshu, Alimi Olawale A, Liu Bo, Krishnan Mena A, Kuss Mitchell, Shi Wei, Krishnamurthy Jairam, Dong Jianghu James, Oberley-Deegan Rebecca E, Duan Bin
Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Pharmaceuticals (Basel). 2025 Aug 5;18(8):1159. doi: 10.3390/ph18081159.
: Chemotherapy-induced neuropathic pain (CINP) represents a critical challenge in oncology, emerging as a common and debilitating side effect of widely used chemotherapeutic agents, such as paclitaxel (PTX). Current therapeutic interventions and preventive strategies for CINP are largely insufficient, as they fail to address the underlying peripheral nerve damage, highlighting an urgent need for the development of new drugs. This study aimed to investigate the dual-function effects on normal cell protection and tumor suppression of BMX-001, a redox-active manganese metalloporphyrin that has demonstrated antioxidant and anti-inflammatory properties, which offers potential in protecting central nervous system tissues and treating CINP. : This study assessed BMX-001's different roles in protecting normal cells while acting as a pro-oxidant and pro-inflammatory molecule in cancer cells in vitro. We also evaluated its neuroprotective effect in preclinical PTX-induced CINP models in vivo. : Our results showed significant reductions in mechanical and cold allodynia, decreased pro-inflammatory cytokine levels, and restored antioxidant capacity in peripheral nerves and dorsal root ganglia (DRGs) following BMX-001 treatment. : Overall, our study highlights the therapeutic potential of BMX-001 to mitigate CINP and enhance anticancer efficiency. Its dual-selective mechanism supports the future clinical investigation of BMX-001 as a novel adjunct to chemotherapeutic regimens.
化疗诱导的神经性疼痛（CINP）是肿瘤学中的一项严峻挑战，它是广泛使用的化疗药物（如紫杉醇（PTX））常见且使人衰弱的副作用。目前针对CINP的治疗干预措施和预防策略在很大程度上并不充分，因为它们未能解决潜在的周围神经损伤问题，这凸显了开发新药的迫切需求。本研究旨在探究具有氧化还原活性的锰金属卟啉BMX - 001对正常细胞保护和肿瘤抑制的双重作用，该物质已证明具有抗氧化和抗炎特性，在保护中枢神经系统组织和治疗CINP方面具有潜力。本研究评估了BMX - 001在体外保护正常细胞同时作为癌细胞中的促氧化剂和促炎分子的不同作用。我们还在体内临床前PTX诱导的CINP模型中评估了其神经保护作用。我们的结果显示，BMX - 001治疗后，机械性和冷觉异常性疼痛显著减轻，促炎细胞因子水平降低，周围神经和背根神经节（DRG）的抗氧化能力恢复。总体而言，我们的研究突出了BMX - 001减轻CINP和提高抗癌效率的治疗潜力。其双重选择性机制支持将BMX - 001作为化疗方案新型辅助药物的未来临床研究。
