Docetaxel (DT) has been reported to positive therapeutic actions in the treatment of glioblastoma, breast tumors, and prostate cancers. However, it can also induce peripheral neuropathic pain and neurotoxicity as adverse effects. Expression level of TRPV1 cation channel is high in dorsal root ganglion (DRG), and its activation via capsaicin and reactive oxygen species (ROS) mediates peripheral neuropathic pain in mice. As cancer is known to increase the levels of ROS, the protective roles of melatonin (MT) and selenium (Se) were evaluated on the TRPV1-mediated neurotoxicity and pain in the DT-treated mice. Mice and TRPV1 expressing SH-SY5Y cells were equally divided into control, MT, Se, DT, DT+MT, and DT+Se groups. In the results of pain tests in the mice, we observed a decrease in DT-mediated mechanical and heat neuropathic pain by MT and Se. The results of plate reader assay and laser confocal microscopy image analyses indicated a protective role of MT and Se on the DT-induced increase of mitochondrial ROS, cytosolic ROS, apoptosis, lipid peroxidation, intracellular free Zn2+, Ca2+, and caspase-3 and -9 levels in the DRG and SH-SY5Y cells. MT and Se modulated DT-induced decreases of total antioxidant status, reduced glutathione and glutathione peroxidase in the DRG. However, the effects of DT were not observed in the non-TRPV1 expressing SH-SY5Y cells. Hence, MT and Se mediated protective effects against DT-induced adverse peripheral oxidative neurotoxicity and peripheral pain. These effects may be attributed to potent antioxidant properties of MT and Se.

中文翻译：

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褪黑激素和硒在小鼠中抑制多西紫杉醇诱导的 TRPV1 激活、神经性疼痛和氧化性神经毒性。

据报道，多西他赛 (DT) 在治疗胶质母细胞瘤、乳腺肿瘤和前列腺癌中具有积极的治疗作用。然而，它也可以诱发周围神经性疼痛和神经毒性作为副作用。TRPV1 阳离子通道在背根神经节 (DRG) 中的表达水平较高，其通过辣椒素和活性氧 (ROS) 的激活介导了小鼠的周围神经性疼痛。由于已知癌症会增加 ROS 的水平，因此在 DT 治疗的小鼠中评估了褪黑激素 (MT) 和硒 (Se) 对 TRPV1 介导的神经毒性和疼痛的保护作用。小鼠和表达 TRPV1 的 SH-SY5Y 细胞被平均分为对照组、MT、Se、DT、DT+MT 和 DT+Se 组。在小鼠疼痛测试的结果中，我们观察到 MT 和 Se 导致 DT 介导的机械性和热性神经性疼痛减少。酶标仪检测和激光共聚焦显微镜图像分析的结果表明 MT 和 Se 对 DT 诱导的线粒体 ROS、细胞溶质 ROS、细胞凋亡、脂质过氧化、细胞内游离 Zn2+、Ca2+ 和 caspase-3 增加具有保护作用和 - DRG 和 SH-SY5Y 细胞中有 9 个水平。MT 和硒调节 DT 诱导的总抗氧化状态降低、DRG 中谷胱甘肽和谷胱甘肽过氧化物酶减少。然而，在不表达 TRPV1 的 SH-SY5Y 细胞中未观察到 DT 的影响。因此，MT 和 Se 介导了对 DT 诱导的不利外周氧化神经毒性和外周疼痛的保护作用。这些作用可能归因于 MT 和 Se 的强大抗氧化特性。