Aims

The present study was designed to investigate whether the antinociceptive effect of bone marrow-derived mesenchymal stem/stromal cells (MSC) during oxaliplatin (OXL)-induced sensory neuropathy is related to antioxidant properties.

Main methods

Male mice C57BL/6 were submitted to repeated intravenous administration of OXL (1 mg/kg, 9 administrations). After the establishment of sensory neuropathy, mice were treated with a single intravenous administration of MSC (1 × 10⁶), vehicle or gabapentin. Paw mechanical and thermal nociceptive thresholds were evaluated through von Frey filaments and cold plate test, respectively. Motor performance was evaluated in the rota-rod test. Gene expression profile, cytokine levels, and oxidative stress markers in the spinal cord were evaluated by real-time PCR, ELISA and biochemical assays, respectively.

Key findings

OXL-treated mice presented behavioral signs of sensory neuropathy, such as mechanical allodynia and thermal hyperalgesia, which were completely reverted by a single administration of MSC. Repeated oral treatment with gabapentin (70 mg/kg) induced only transient antinociception. The IL-1β and TNF-α spinal levels did not differ between mice with or without sensory neuropathy. MSC increased the levels of anti-inflammatory cytokines, IL-10 and TGF-β, in the spinal cord of neuropathic mice, in addition to increasing the gene expression of antioxidant factors SOD and Nrf-2. Additionally, nitrite and MDA spinal levels were reduced by the MSC treatment.

Significance

MSC induce reversion of sensory neuropathy induced by OXL possibly by activation of anti-inflammatory and antioxidant pathways, leading to reestablishment of redox homeostasis in the spinal cord.

中文翻译：

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间充质干细胞通过在脊髓中建立氧化还原稳态来减少奥沙利铂诱导的感觉神经病

目的

本研究旨在调查在奥沙利铂（OXL）诱导的感觉神经病过程中骨髓来源的间充质干/基质细胞（MSC）的抗伤害感受作用是否与抗氧化剂特性相关。

主要方法

使雄性小鼠C57BL / 6重复静脉内施用OLX（1mg / kg，9次施用）。感觉神经病建立后，小鼠通过单次静脉内注射MSC（1×10 ⁶），媒介物或加巴喷丁进行治疗。通过冯·弗雷丝和冷板试验分别评估了爪的机械和热伤害阈值。通过旋转杆测试评估电机性能。分别通过实时PCR，ELISA和生化分析评估了脊髓中的基因表达谱，细胞因子水平和氧化应激标志物。

主要发现

OXL处理的小鼠表现出感觉神经病的行为体征，例如机械性异常性疼痛和热痛觉过敏，通过单次施用MSC即可完全恢复。加巴喷丁（70 mg / kg）的反复口服治疗仅诱发短暂的镇痛作用。在有或没有感觉神经病的小鼠之间，IL-1β和TNF-α脊髓水平没有差异。MSC除了增加抗氧化因子SOD和Nrf-2的基因表达外，还增加了神经性小鼠脊髓中抗炎细胞因子IL-10和TGF-β的水平。另外，通过MSC治疗降低了亚硝酸盐和MDA脊髓水平。

意义

MSC可能通过激活抗炎和抗氧化途径来诱导OXL诱导的感觉神经病的逆转，从而导致脊髓中氧化还原稳态的重建。