Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alborz University of Medical Sciences, Karaj, Iran.
Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Daru. 2022 Dec;30(2):303-310. doi: 10.1007/s40199-022-00448-6. Epub 2022 Sep 15.
Peripheral neuropathy is a dose-limiting adverse effect of vincristine (VCR) in cancer chemotherapies. Dapsone is commonly used for the prevention of opportunistic infections following cancer therapies. Therefore, a high rate of VCR and dapsone co-administration has occurred in leukemias. Recently neuroprotective effects of dapsone have been reported in various diseases.
Regarding the physiopathology of VCR-induced peripheral neuropathy (VIPN) and dapsone neuroprotection, this study evaluated the effect of dapsone on VIPN.
VIPN was induced by VCR injection (0.5 mg/kg IP, every other day, 1 week) in male Wistar rats. In the treatment group, dapsone(12.5 mg/kg IP, 1 week) was injected 30 min before VCR. Hot plate, Von Frey, motor neuron conduction velocity (MNCV), and histopathological tests were applied. The levels of TNF-α and NF-kB in the sciatic nerve and caspase-3 activity in dorsal root ganglion were measured by the ELISA method. The levels of malondialdehyde (MDA) and Glutathione (GSH) in the sciatic nerve were measured by spectrophotometry and colorimetric assays.
VIPN was observed as araised thermal and mechanical threshold, reduced MNCV, and sciatic nerve demyelination. However, dapsone reduced the mechanical and thermal threshold and improved the MNCV. Also, dapsone reduced TNF-α, NF-kB, MDA, and Caspase-3 activity, and increased the GSH level in the sciatic nerve. Moreover, dapsone prevented VCR-induced demyelination in the sciatic nerve.
This research demonstrated that dapsone could be used as a protective drug against VIPN. It improves the impaired thermal and mechanical sensations by reducing inflammatory, oxidant, and apoptosis factors and preventing demyelination in the sciatic nerve.
周围神经病变是癌症化疗中长春新碱（VCR）的剂量限制不良反应。氨苯砜常用于预防癌症治疗后的机会性感染。因此，白血病中 VCR 和氨苯砜的联合用药率很高。最近，氨苯砜在各种疾病中的神经保护作用已被报道。
鉴于长春新碱诱导的周围神经病变（VIPN）和氨苯砜神经保护的病理生理学，本研究评估了氨苯砜对 VIPN 的影响。
雄性 Wistar 大鼠通过 VCR 注射（0.5mg/kg IP，每隔一天，1 周）诱导 VIPN。在治疗组中，在 VCR 前 30 分钟注射氨苯砜（12.5mg/kg IP，1 周）。应用热板、Von Frey、运动神经元传导速度（MNCV）和组织病理学测试。通过 ELISA 法测量坐骨神经中的 TNF-α 和 NF-kB 水平以及背根神经节中的 caspase-3 活性。通过分光光度法和比色法测量坐骨神经中的丙二醛（MDA）和谷胱甘肽（GSH）水平。
VIPN 表现为热和机械阈值升高、MNCV 降低和坐骨神经脱髓鞘。然而，氨苯砜降低了机械和热阈值并改善了 MNCV。此外，氨苯砜降低了坐骨神经中的 TNF-α、NF-kB、MDA 和 Caspase-3 活性，并增加了 GSH 水平。此外，氨苯砜可预防 VCR 诱导的坐骨神经脱髓鞘。
本研究表明，氨苯砜可用作 VIPN 的保护药物。它通过降低炎症、氧化和凋亡因子并防止坐骨神经脱髓鞘来改善受损的热和机械感觉。
