Department of Histology and Embryology, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey.
Department of Biophysics, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey.
Neurotox Res. 2023 Dec;41(6):638-647. doi: 10.1007/s12640-023-00657-0. Epub 2023 Jul 13.
Diabetic neuropathy (DNP) is a severe complication of diabetes mellitus. In this study, we examined the potential of hesperidin (HES) to attenuate DNP and the involvement of the TRPM2 channel in this process. The rats were given a single dose of 45 mg/kg of streptozotocin (STZ) intraperitoneally to induce diabetic neuropathic pain. On the third day, we confirmed the development of diabetes in the DNP and DNP + HES groups. The HES groups were treated with 100 mg/kg and intragastric gavage daily for 14 days. The results showed that treatment with HES in diabetic rats decreased STZ-induced hyperglycemia and thermal hyperalgesia. Furthermore, in the histopathological examination of the sciatic nerve, HES treatment reduced STZ-induced damage. The immunohistochemical analysis also determined that STZ-induced increased TRPM2 channel, type-4 collagen, and fibrinogen immunoactivity decreased with HES treatment. In addition, we investigated the TRPM2 channel activation in the sciatic nerve damage mechanism of DNP model rats created by STZ application using the ELISA method. We determined the regulatory effect of HES on increased ROS, and PARP1 and TRPM2 channel activation in the sciatic nerves of DNP model rats. These findings indicated that hesperidin treatment could attenuate diabetes-induced DNP by reducing TRPM2 channel activation.
糖尿病性神经病 (DNP) 是糖尿病的一种严重并发症。在这项研究中，我们研究了橙皮苷 (HES) 减轻 DNP 的潜力及其在该过程中涉及的瞬时受体电位阳离子通道 M2 (TRPM2) 通道。大鼠腹腔内给予单次 45mg/kg 链脲佐菌素 (STZ) 诱导糖尿病性神经痛。第三天，我们确认 DNP 和 DNP+HES 组发生了糖尿病。HES 组以 100mg/kg 剂量灌胃，每天 14 天。结果表明，HES 治疗可降低糖尿病大鼠的 STZ 诱导性高血糖和热痛觉过敏。此外，在坐骨神经的组织病理学检查中，HES 治疗减轻了 STZ 诱导的损伤。免疫组织化学分析还确定，HES 治疗可降低 STZ 诱导的 TRPM2 通道、IV 型胶原和纤维蛋白原免疫活性增加。此外，我们使用 ELISA 法研究了 STZ 应用于 DNP 模型大鼠造成的坐骨神经损伤机制中 TRPM2 通道的激活。我们确定了 HES 对 DNP 模型大鼠坐骨神经中增加的 ROS、PARP1 和 TRPM2 通道激活的调节作用。这些发现表明，橙皮苷治疗可通过降低 TRPM2 通道的激活来减轻糖尿病引起的 DNP。
