Creanga-Murariu Ioana, Filipiuc Leontina-Elena, Gogu Maria-Raluca, Ciorpac Mitica, Cumpat Carmen Marinela, Tamba Bogdan-Ionel, Alexa-Stratulat Teodora
Advanced Research and Development Center for Experimental Medicine (CEMEX), Iasi, Romania.
Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania.
Front Pharmacol. 2024 Jun 12;15:1395951. doi: 10.3389/fphar.2024.1395951. eCollection 2024.
Chemotherapy-induced peripheral neuropathy (CIPN) is a shared burden for 68.1% of oncological patients undergoing chemotherapy with Paclitaxel (PTX). The symptoms are intense and troublesome, patients reporting paresthesia, loss of sensation, and dysesthetic pain. While current medications focus on decreasing the symptom intensity, often ineffective, no medication is yet recommended by the guidelines for the prevention of CIPN. Cannabinoids are an attractive option, as their neuroprotective features have already been demonstrated in neuropathies with other etiologies, by offering the peripheral neurons protection against toxic effects, which promotes analgesia. We aim to screen several new cannabinoids for their potential use as neuroprotective agents for CIPN by investigating the cellular toxicity profile and by assessing the potential neuroprotective features against PTX using a primary dorsal root ganglion neuronal culture. Our study showed that synthetic cannabinoids JWH-007, AM-694 and MAB-CHMINACA and phytocannabinoids Cannabixir Medium dried flowers (NC1) and Cannabixir THC full extract (NC2) preserve the viability of fibroblasts and primary cultured neurons, in most of the tested dosages and time-points. The combination between the cannabinoids and PTX conducted to a cell viability of 70%-89% compared to 40% when PTX was administered alone for 48 h. When assessing the efficacy for neuroprotection, the combination between cannabinoids and PTX led to better preservation of neurite length at all tested time-points compared to controls, highly drug and exposure-time dependent. By comparison, the combination of the cannabinoids and PTX administered for 24 h conducted to axonal shortening between 23% and 44%, as opposed to PTX only, which shortened the axons by 63% compared to their baseline values. Cannabinoids could be potential new candidates for the treatment of paclitaxel-induced peripheral neuropathy; however, our findings need to be followed by additional tests to understand the exact mechanism of action, which would support the translation of the cannabinoids in the oncological clinical practice.
化疗引起的周围神经病变（CIPN）是68.1%接受紫杉醇（PTX）化疗的肿瘤患者共同面临的负担。症状严重且令人困扰，患者报告有感觉异常、感觉丧失和感觉迟钝性疼痛。虽然目前的药物专注于减轻症状强度，但往往无效，指南中尚未推荐用于预防CIPN的药物。大麻素是一个有吸引力的选择，因为它们的神经保护特性已在其他病因的神经病变中得到证实，通过为周围神经元提供保护以对抗毒性作用，从而促进镇痛。我们旨在通过研究细胞毒性概况，并使用原代背根神经节神经元培养评估对PTX的潜在神经保护特性，来筛选几种新的大麻素作为CIPN神经保护剂的潜在用途。我们的研究表明，合成大麻素JWH - 007、AM - 694和MAB - CHMINACA以及植物大麻素Cannabixir中等干花（NC1）和Cannabixir THC全提取物（NC2）在大多数测试剂量和时间点都能保持成纤维细胞和原代培养神经元的活力。与单独给予PTX 48小时时40%的细胞活力相比，大麻素与PTX联合使用时细胞活力为70% - 89%。在评估神经保护功效时，与对照组相比，大麻素与PTX联合使用在所有测试时间点都能更好地保持神经突长度，高度依赖药物和暴露时间。相比之下，大麻素与PTX联合使用24小时导致轴突缩短23%至44%，而仅使用PTX时，轴突与基线值相比缩短了63%。大麻素可能是治疗紫杉醇引起的周围神经病变的潜在新候选药物；然而，我们的发现还需要后续的额外测试来了解确切的作用机制，这将支持大麻素在肿瘤临床实践中的转化应用。
