Çiğ Bilal
Kirsehir Ahi Evran University Medicine Faculty Department of Physiology, Kirsehir, Türkiye.
Front Pharmacol. 2025 Mar 7;16:1549190. doi: 10.3389/fphar.2025.1549190. eCollection 2025.
Many drugs preferred for pain relief are insufficient against oxaliplatin (OX) induced neuropathic pain (OX-IN). Studies have shown that such pain mediators as the TRPV1 channel play a critical role in triggering high-sensitivity pain response in the dorsal root ganglia (DRG). TRPV1 activated by oxidative stress increases cytosolic free Ca levels and leads to apoptotic cell damage. The key factors involved in the pathophysiology of OX-IN, which involves many components, are mitochondrial dysfunction and oxidative stress, both triggered by excessive Ca influx across the neuronal membrane. Selenium (Se), an essential trace element, prevents the harmful effects of this oxidative stress through glutathione peroxidase. This study is based on understanding the neuroprotective role of Se, a cofactor for glutathione peroxidase, against TRPV1-mediated oxidative damage, mitochondrial dysfunction and apoptosis in OX-IN using molecular techniques such as patch clamp. The primary target in this study was DRGs as the initial station of OX-induced peripheral pain isolated in adult rats. In addition to the SN (sciatic) neurons isolated from the same animals, breast cancer cell (MCF-7) was also used to confirm the results. The study was conducted with four groups: control (5% dextrose), OX (4 mg/kg OX twice a week), Se (1.5 mg/kg Se every other day) and finally OX + Se, all of which were administered to the animals intraperitoneally for 4 weeks. The OX (50 μM for 24 h) and Se (200 nM for 2 h) were applied to MCF-7 cells . Although an excessive increase was observed in Tumour necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as mitochondrial oxidative stress, apoptosis and TRPV1 channel overactivations in DRG and SN neurons under OX treatment, Se suppressed these negative effects. While OX reduced glutathione peroxidase and significantly increased malondialdehyde level (LP) in DRG neurons, Se reversed this situation. In conclusion, the TRPV1-mediated efficacy of Se in suppressing OX-induced pain symptoms was demonstrated and we concluded that Se should be considered in future therapeutic approaches in the treatment of OX-IN.
许多常用于缓解疼痛的药物对奥沙利铂（OX）诱导的神经性疼痛（OX-IN）疗效欠佳。研究表明，诸如TRPV1通道等疼痛介质在触发背根神经节（DRG）的高敏疼痛反应中起关键作用。由氧化应激激活的TRPV1会增加胞质游离钙水平，并导致细胞凋亡性损伤。OX-IN的病理生理学涉及多个成分，其中的关键因素是线粒体功能障碍和氧化应激，二者均由过量钙离子跨神经元膜内流引发。硒（Se）作为一种必需微量元素，可通过谷胱甘肽过氧化物酶预防这种氧化应激的有害影响。本研究旨在利用膜片钳等分子技术，了解谷胱甘肽过氧化物酶的辅助因子硒对OX-IN中TRPV1介导的氧化损伤、线粒体功能障碍和细胞凋亡的神经保护作用。本研究的主要靶点是成年大鼠体内分离出的DRG，它是OX诱导的外周疼痛的起始部位。除了从同一动物体内分离出的坐骨神经（SN）神经元外，还使用乳腺癌细胞（MCF-7）来验证结果。本研究分为四组进行：对照组（5%葡萄糖）、OX组（每周两次，每次4mg/kg OX）、Se组（隔日一次，每次1.5mg/kg Se），最后是OX + Se组，所有处理均通过腹腔注射给药，持续4周。将OX（50μM，作用24小时）和Se（200nM，作用2小时）应用于MCF-7细胞。尽管在OX处理下，DRG和SN神经元中的肿瘤坏死因子α（TNF-α）﹑白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）以及线粒体氧化应激、细胞凋亡和TRPV1通道过度激活均出现过度增加，但Se可抑制这些负面影响。虽然OX降低了DRG神经元中的谷胱甘肽过氧化物酶，并显著提高了丙二醛水平（LP），但Se扭转了这种情况。总之，本研究证明了硒在抑制OX诱导的疼痛症状方面具有TRPV1介导的功效，我们得出结论，在未来OX-IN的治疗方法中应考虑使用硒。
