Vincristine (VCR) is commonly used to treat a variety of hematological malignancies and solid tumors in pediatric and adult patients. However, peripheral neuropathy is a dose-limiting side effect that leaves some patients with functional disability and long-term pain. Oxytocin (OT) has demonstrated analgesic and anti-inflammatory properties, but there is no evidence regarding its effects on VCR-induced neurotoxicity. Therefore, we evaluated the potential protective effects of OT on VCR-induced neurotoxicity. In vitro, VCR (0.005 ∼ 0.1 µmol/l) and OT (10-8 ∼ 10-5 mol/l) were added into cultured primary dorsal root ganglion (DRG) neurons of mice. The length of neurites was counted by using immunofluorescence. In vivo, neurotoxicity was induced in mice by administration of VCR (0.1 mg/kg, intraperitoneal injection for 14 days) with or without pretreatment of OT (0.1 mg/kg or 1 mg/kg). Atosiban, an OT receptor (OTR) antagonist and OTR knockout (KO) mice were used for evaluating effects of OTR. Mechanical hyperalgesia was measured by using von Frey filaments. Histology of plantar skin, sciatic nerve and DRG was observed by using transmission electron microscopy (TEM) and hematoxylin-eosin (HE) staining. Results indicated that OT alleviated VCR-induced neurite damage in cultured primary DRG neurons in vitro. In vivo, OT ameliorated VCR-induced hyperalgesia. Histologically, OT attenuated the VCR-induced damages of nerve endings, myelin sheaths and Schwann cells in sciatic nerve and DRG. These effects were antagonized by atosiban. In addition, OTR knockout mice exhibited more severe hyperalgesia than wild-type mice. Globally, these results indicated that OT may have neuroprotective effects on vincristine-induced neurotoxicity in mice.

中文翻译：

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催产素对长春新碱诱导的小鼠神经毒性的神经保护作用

长春新碱 (VCR) 通常用于治疗儿童和成人患者的各种血液系统恶性肿瘤和实体瘤。然而，周围神经病变是一种剂量限制性副作用，会导致一些患者出现功能障碍和长期疼痛。催产素 (OT) 已显示出镇痛和抗炎特性，但没有证据表明其对 VCR 诱导的神经毒性的影响。因此，我们评估了 OT 对 VCR 诱导的神经毒性的潜在保护作用。在体外，将VCR（0.005 ∼ 0.1 µmol/l）和OT（10-8 ∼ 10-5 mol/l）加入到培养的小鼠原代背根神经节（DRG）神经元中。使用免疫荧光计数神经突的长度。在体内，通过施用 VCR（0.1 mg/kg，腹腔注射 14 天）有或没有 OT 预处理（0.1 毫克/公斤或 1 毫克/公斤）。阿托西班，一种 OT 受体 (OTR) 拮抗剂和 OTR 敲除 (KO) 小鼠用于评估 OTR 的效果。机械痛觉过敏是通过使用von Frey细丝来测量的。使用透射电子显微镜（TEM）和苏木精-伊红（HE）染色观察足底皮肤、坐骨神经和背根神经节的组织学。结果表明，OT 减轻了体外培养的原代 DRG 神经元中 VCR 诱导的神经突损伤。在体内，OT 改善了 VCR 诱导的痛觉过敏。在组织学上，OT 减弱了 VCR 诱导的坐骨神经和背根神经节中神经末梢、髓鞘和雪旺细胞的损伤。这些作用被阿托西班拮抗。此外，OTR 基因敲除小鼠表现出比野生型小鼠更严重的痛觉过敏。在全球范围内，