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Effect of Hesperidin on Sciatic Nerve Damage in STZ-Induced Diabetic Neuropathy: Modulation of TRPM2 Channel

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Abstract

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.

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Funding

This study was supported by Van Yuzuncu Yil University Scientific Research Projects Coordinatorship as TYL-2022–10175 project number.

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All authors designed the study and performed the experiments. FA and MHB performed histology and IHC analyses. KY wrote the main manuscript text and performed the biochemical analysis. All the authors reviewed the manuscript.

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Correspondence to Kenan Yıldızhan.

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The authors declare no competing interests.

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This study was presented as an oral presentation to the 12th International Medicine and Heath Sciences Researches Congress on 18-19 March 2023, Ankara, Turkey, by Autor’s. The results of the current study were summarized from the master's thesis of MHB.

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Bayir, M.H., Yıldızhan, K. & Altındağ, F. Effect of Hesperidin on Sciatic Nerve Damage in STZ-Induced Diabetic Neuropathy: Modulation of TRPM2 Channel. Neurotox Res 41, 638–647 (2023). https://doi.org/10.1007/s12640-023-00657-0

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  • DOI: https://doi.org/10.1007/s12640-023-00657-0

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