Cuozzo Mariarosaria, Castelli Vanessa, Avagliano Carmen, Cimini Annamaria, d'Angelo Michele, Cristiano Claudia, Russo Roberto
Department of Pharmacy, University of Naples Federico II, 80131 Napoli, Italy.
Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Biomedicines. 2021 Mar 30;9(4):346. doi: 10.3390/biomedicines9040346.
Chemotherapy-induced peripheral neuropathy (CIPN) represents one of the most prevalent and potentially disabling side effects due to the use of anticancer drugs, one of the primary neuropathies detected is peripheral neuropathy induced by administration of taxanes, including paclitaxel. It has been demonstrated that gut microbiota is crucial for the therapeutic effect of chemotherapeutic drugs for inhibiting tumor growth and contributed to the pathogenesis of the CIPN. The use of nutraceuticals has receiving growing attention from the research community due to their phytochemical, biological, and pharmacological properties. It has been demonstrated that probiotic formulations may both reduce inflammation and modulate the expression of pain receptors. Our studies tested the efficacy of a probiotic formulation, SLAB51, in preventing paclitaxel-induced neuropathy. Interestingly, our probiotic formulation was able to keep the gut integrity, preserving its functionality, in CIPN-mice, moreover, it prevented the mechanical and cold hypersensitivity induced in paclitaxel-mice. Additionally, ex-vivo analysis showed that in CIPN-mice the pro-biotic treatment increased the expression of opioid and cannabinoid receptors in spinal cord, it prevented in the reduction in nerve fiber damage in the paws and modulated the serum proinflammatory cytokines concentration. On basis of these data, the use of this specific probiotic formulation may represent a valid adjuvant agent to paclitaxel, useful and not toxic for long-lasting therapies.
化疗引起的周围神经病变（CIPN）是使用抗癌药物导致的最常见且可能致残的副作用之一，检测到的主要神经病变之一是紫杉烷类药物（包括紫杉醇）给药引起的周围神经病变。已证明肠道微生物群对于化疗药物抑制肿瘤生长的治疗效果至关重要，并与CIPN的发病机制有关。由于其植物化学、生物学和药理学特性，营养保健品的使用受到了研究界越来越多的关注。已证明益生菌制剂可能既减轻炎症又调节疼痛受体的表达。我们的研究测试了一种益生菌制剂SLAB51预防紫杉醇引起的神经病变的功效。有趣的是，我们的益生菌制剂能够在CIPN小鼠中保持肠道完整性，维持其功能，此外，它还能预防紫杉醇小鼠中诱导的机械性和冷超敏反应。此外，体外分析表明，在CIPN小鼠中，益生菌治疗增加了脊髓中阿片类和大麻素受体的表达，防止了爪部神经纤维损伤的减少，并调节了血清促炎细胞因子浓度。基于这些数据，使用这种特定的益生菌制剂可能是紫杉醇的一种有效的辅助剂，对长期治疗有用且无毒。
