TY - JOUR A2 - Suga, Hirotaka AU - Oliveira, Anna Lethicia L. AU - Santos, Gisele G. L. AU - Espirito-Santo, Renan F. AU - Silva, Gessica Sabrina A. AU - Evangelista, Afrânio F. AU - Silva, Daniela N. AU - Soares, Milena B. P. AU - Villarreal, Cristiane Flora PY - 2021 DA - 2021/01/07 TI - Reestablishment of Redox Homeostasis in the Nociceptive Primary Afferent as a Mechanism of Antinociception Promoted by Mesenchymal Stem/Stromal Cells in Oxaliplatin-Induced Chronic Peripheral Neuropathy SP - 8815206 VL - 2021 AB - Painful neuropathy is a common adverse effect of oxaliplatin (OXL), a platinum-derivative chemotherapeutic agent. Oxidative stress and mitochondrial dysfunction are key factors contributing to the development of OXL-induced peripheral neuropathy (OIPN). Based on the antioxidant and antinociceptive properties of mesenchymal stem/stromal cells (MSC), the present study tested the hypothesis that MSC induce antinociceptive effects during OIPN by promoting regulation of redox environment and mitochondrial homeostasis in the nociceptive primary afferents. C57Bl/6 mice submitted to the OXL-chronic neuropathy induction protocol by repeated intravenous administration of OXL (1 mg/kg) were evaluated to determine the paw mechanical and thermal nociceptive thresholds using the von Frey filaments and cold plate tests, respectively. Two weeks after the neuropathy induction, mice were treated with bone marrow-derived MSC ( 1 × 10. 6. ），载体或加巴亨坦（GBP，70mg / kg）。通过透射电子显微镜，RT-QPCR和生物化学测定，评估四周后，通过透射电子显微镜，RT-QPCR和生物化学测定评估坐骨神经和背根神经节（DRG）中的线粒体形态，基因表达谱和氧化应激标志物。OxL处理的小鼠呈现了感觉神经病变的行为迹象，例如机械异常性疼痛和热痛觉过敏。通过一次施用MSC完全恢复行为疼痛神经病变，而GBP的日常治疗仅诱导短暂的抗血汗效果。OIPN小鼠的坐骨神经和DRG的超微结构分析显示了髓鞘和未髓鞘纤维中的高典型线粒体比例。重要的是，在MSC治疗的神经疗法小鼠中，这种线粒体类缺肌均受到强烈降低。此外，MSC治疗的神经疗法小鼠表现出上调 草皮和 NRF2.坐骨神经和DRG中的mRNA。根据该结果，MSC从OIPN小鼠中减少亚硝酸盐胁迫和脂质过氧化的标记。我们的数据表明，在伤害性主要传入中重新建立氧化还原稳态是MSC移植恢复氧诱导的慢性痛苦神经病变的机制。SN - 1687-966X UR - https://doi.org/10.1155/2021/8815206 do - 10.1155/2021 / 8815206 jf - 干细胞国际pb - hindawi kw - er -