Humanin attenuates metabolic, toxic, and traumatic neuropathic pain in mice by protecting against oxidative stress and increasing inflammatory cytokine

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2024-11-05 DOI:10.1016/j.neuropharm.2024.110207

Batuhan Bilgin , Munevver Gizem Hekim , Ferah Bulut , Muhammed Mirac Kelestemur , Muhammed Adam , Sibel Ozcan , Sinan Canpolat , Ahmet Ayar , Mete Ozcan

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引用次数: 0

Abstract

Neuropathic pain is associated with diverse etiologies, including sciatica, diabetes, and the use of chemotherapeutic agents. Despite the varied origins, mitochondrial dysfunction, oxidative stress, and inflammatory cytokines are recognized as key contributing factors in both the initiation and maintenance of neuropathic pain. The effects of the mitochondrial-derived peptide humanin on neuropathic pain, however, remain unclear, despite its demonstrated influence on these mechanisms in numerous disease models. This study aimed to evaluate the effects of humanin on pain behavior in murine models of metabolic (streptozotocin/STZ), toxic (oxaliplatin/OXA), traumatic (sciatic nerve cuffing/cuff), and neuropathic pain. A secondary objective was to assess whether humanin modulates oxidative damage and inflammatory cytokine levels in these neuropathic pain models.

Humanin (4 mg/kg) was administered intraperitoneally (i.p.) to BALB/c male mice with induced neuropathic pain over a period of 15 days, with pain thresholds assessed using hot plate, cold plate, and Von Frey tests. Serum levels of antioxidant enzymes, oxidative stress markers, and inflammatory/anti-inflammatory cytokines were measured via enzyme-linked immunosorbent assay (ELISA).

In neuropathic pain-induced mice, humanin administration resulted in a statistically significant increase in pain threshold values in the STZ + Humanin, OXA + Humanin, and cuff + Humanin groups compared to their respective control groups (P < 0.05) over 15 days. Furthermore, humanin treatment significantly elevated antioxidant enzyme levels and anti-inflammatory cytokine concentrations, while reducing oxidative stress markers and pro-inflammatory cytokine levels compared to control groups (P < 0.01).

These findings suggest that humanin exhibits therapeutic potential in the treatment of neuropathic pain induced by STZ, OXA, and cuff models. The ability of humanin to mitigate neuropathic pain through the suppression of oxidative stress and inflammatory cytokines indicates its promise as a novel therapeutic strategy.

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人参皂苷通过防止氧化应激和增加炎性细胞因子减轻小鼠的代谢性、毒性和创伤性神经病理性疼痛

神经性疼痛与多种病因有关，包括坐骨神经痛、糖尿病和化疗药物的使用。尽管病因多种多样，但线粒体功能障碍、氧化应激和炎性细胞因子被认为是导致神经性疼痛发生和维持的关键因素。然而，线粒体衍生肽 humanin 对神经病理性疼痛的影响仍不清楚，尽管它在许多疾病模型中都被证明对这些机制有影响。本研究旨在评估人肽对代谢性（链脲佐菌素/STZ）、毒性（奥沙利铂/OXA）和创伤性（坐骨神经袖带/袖套）神经病理性疼痛小鼠模型中疼痛行为的影响。次要目的是评估人胰岛素是否能调节这些神经病理性疼痛模型中的氧化损伤和炎性细胞因子水平。对诱发神经病理性疼痛的 BALB/c 雄性小鼠腹腔注射人参素（4 毫克/千克），为期 15 天，使用热板、冷板和 von Frey 试验评估疼痛阈值。通过酶联免疫吸附试验（ELISA）测定血清中抗氧化酶、氧化应激标记物和炎症/抗炎细胞因子的水平。在神经病理性疼痛诱导的小鼠中，与各自的对照组相比，服用人胰岛素 15 天后，STZ + 人胰岛素组、OXA + 人胰岛素组和袖套 + 人胰岛素组的疼痛阈值均有统计学意义的显著提高（P < 0.05）。此外，与对照组相比，人参皂苷治疗明显提高了抗氧化酶水平和抗炎细胞因子浓度，同时降低了氧化应激标记物和促炎细胞因子水平（P < 0.01）。这些研究结果表明，人参皂苷在治疗由 STZ、OXA 和袖套模型诱发的神经病理性疼痛方面具有治疗潜力。人参皂苷能够通过抑制氧化应激和炎症细胞因子减轻神经性疼痛，这表明它有望成为一种新型治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).