Abstract：
Previous clinical reports have shown that capecitabine, an oral prodrug of 5-fluorouracil (5-Fu), can induce peripheral neuropathy, resulting in numbness, paresthesia and hypoesthesia. However, the mechanism through which capecitabine causes peripheral nerve injury remains unclear. Here, we demonstrate that systemic administration of capecitabine leads to myelin abnormalities in the peripheral nerves of mice, which are possibly attributed to the death of Schwann cells, the myelinating cells in the peripheral nervous system. Furthermore, our results show that 5-Fu induces significant oxidative stress in Schwann cells by inhibiting the expression of the anti-oxidative protein DJ-1, leading to a decrease in Schwann cell markers. We found that the anti-oxidant dihydromyricetin (DMY) reverses 5-Fu-induced Schwann cell death and oxidative stress and alleviates capecitabine-induced myelin abnormalities. Taken together, our data indicate that capecitabine induces peripheral myelin dysfunction by regulating DJ-1-mediated oxidative stress in Schwann cells and reveal DMY as a potential therapeutic strategy for capecitabine-induced peripheral neuropathy.
摘要：
以前的临床报告显示，卡培他滨，5-氟尿嘧啶（5-Fu）的口服前药，可以诱发周围神经病变，导致麻木，感觉异常和感觉减退。然而,卡培他滨引起周围神经损伤的机制尚不清楚.这里,我们证明，全身给药卡培他滨导致小鼠周围神经髓鞘异常，这可能归因于雪旺氏细胞的死亡，周围神经系统的髓鞘细胞。此外，我们的结果表明，5-Fu通过抑制抗氧化蛋白DJ-1的表达在雪旺氏细胞中诱导显著的氧化应激，导致雪旺氏细胞标志物的减少。我们发现抗氧化剂二氢杨梅素（DMY）逆转了5-Fu诱导的雪旺氏细胞死亡和氧化应激，并减轻了卡培他滨诱导的髓鞘异常。一起来看,我们的数据表明,卡培他滨通过调节DJ-1介导的雪旺细胞氧化应激诱导外周髓鞘功能障碍,并揭示DMY是卡培他滨诱导的周围神经病变的潜在治疗策略.
