Minocycline Acts as a Neuroprotective Agent Against Tramadol-Induced Neurodegeneration: Behavioral and Molecular Evidence.

IF 1.7 Q2 MEDICINE, GENERAL & INTERNAL

International Journal of Preventive Medicine Pub Date : 2024-09-28 eCollection Date: 2024-01-01 DOI:10.4103/ijpvm.ijpvm_10_24

Mina Gholami, Zahra Ghelichkhani, Reza Aghakhani, Daniel J Klionsky, Ozra Motaghinejad, Majid Motaghinejad, Mohammad Kazem Koohi, Jalal Hassan

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引用次数: 0

Abstract

Background: Previous evidence indicates that tramadol (TRA) can lead to neurodegenerative events and minocycline (MIN) has neuroprotective properties.

Aim of the study: The current research evaluated the neuroprotective effects of MIN for TRA-promoted neurodegeneration.

Methods: Sixty adult male rats were placed into the following groups: 1 (received 0.7 ml/rat of normal saline, IP), 2 (received 50 mg/kg of TRA, i.p.), 3, 4, 5 (administered TRA as 50 mg/kg simultaneously with MIN at 20, 40, and 60 mg/kg, IP, respectively), and 6 (received MIN alone as 60 mg/kg, IP). The treatment procedure was 21 days. An open field test (OFT) was used to measure motor activity and anxiety-related behavior. Furthermore, oxidative stress; hippocampal inflammation; apoptotic parameters as well as activity of mitochondrial complexes I, II, III, and IV; ATP levels; and mitochondrial membrane potential (MMP) were evaluated. In addition, histomorphological alteration was assessed in two regions of the hippocampus: Cornu Ammonis (CA1) and dentate gyrus (DG).

Results: MIN treatment could inhibit TRA-induced anxiety and motor activity disturbances (P < 0.05). In addition, MIN could attenuate reactive oxygen species (ROS), H₂O₂, oxidized glutathione (GSSG), and malondialdehyde (MDA) level (P < 0.05), while there was increased reduced glutathione (GSH), total antioxidant capacity (TAC), ATP, MMP, and BCL2 levels (P < 0.05) and also elevation of SOD, GPX, GSR (P < 0.05), and mitochondrial complexes I, II, III, and IV activity (P < 0.05) in TRA-treated rats. In consistence with these findings, MIN could reduce TNF/TNF-α, IL1B/IL1-β, BAX, and CASP3 levels (P < 0.05) in TRA-treated rats. MIN also restored the quantitative (P < 0.05) and qualitative histomorphological sequels of TRA in both CA1 and DG areas of the hippocampus.

Conclusions: MIN probably has repositioning capability for inhibition of TRA-induced neurodegeneration via modulation of inflammation, oxidative stress, apoptosis, and mitochondrial disorders.

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米诺环素是一种神经保护剂，可防止曲马多诱发的神经退行性变：行为和分子证据。

背景：以往的证据表明曲马多（TRA）可导致神经退行性病变，而米诺环素（MIN）具有神经保护作用：本研究评估了米诺环素（MIN）对曲马多（TRA）引发的神经退行性病变的神经保护作用：将 60 只成年雄性大鼠分为以下几组：1 组（接受 0.7 ml/只大鼠的生理盐水，IP）、2 组（接受 50 mg/kg 的 TRA，i.p.）、3 组、4 组、5 组（接受 50 mg/kg 的 TRA 的同时分别接受 20、40 和 60 mg/kg 的 MIN，IP）和 6 组（单独接受 60 mg/kg 的 MIN，IP）。治疗过程为 21 天。采用开阔地测试（OFT）来测量运动活动和焦虑相关行为。此外，还评估了氧化应激、海马炎症、细胞凋亡参数以及线粒体复合物 I、II、III 和 IV 的活性、ATP 水平和线粒体膜电位 (MMP)。此外，还评估了海马两个区域的组织形态学变化：结果：MIN 治疗可抑制 TRA 引起的焦虑：结果：MIN治疗可抑制TRA诱发的焦虑和运动活动障碍（P < 0.05）。此外，MIN 还能降低活性氧（ROS）、H2O2、氧化谷胱甘肽（GSSG）和丙二醛（MDA）水平（P < 0.05），同时提高还原谷胱甘肽（GSH）、总抗氧化能力（TAC）、ATP、MMP 和 BCL2 水平（P < 0.05），TRA 处理的大鼠的 SOD、GPX、GSR（P < 0.05）和线粒体复合物 I、II、III 和 IV 活性也有所提高（P < 0.05）。与这些发现一致的是，MIN 可降低 TRA 治疗大鼠的 TNF/TNF-α、IL1B/IL1-β、BAX 和 CASP3 水平（P < 0.05）。MIN 还恢复了 TRA 在海马 CA1 和 DG 区域的定量（P < 0.05）和定性组织形态学后果：结论：MIN可能具有重新定位能力，可通过调节炎症、氧化应激、细胞凋亡和线粒体紊乱来抑制TRA诱导的神经退行性变。

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

International Journal of Preventive Medicine MEDICINE, GENERAL & INTERNAL-

CiteScore

3.20

自引率

4.80%

发文量

107

期刊介绍： International Journal of Preventive Medicine, a publication of Isfahan University of Medical Sciences, is a peer-reviewed online journal with Continuous print on demand compilation of issues published. The journal’s full text is available online at http://www.ijpvmjournal.net. The journal allows free access (Open Access) to its contents and permits authors to self-archive final accepted version of the articles on any OAI-compliant institutional / subject-based repository. The journal will cover technical and clinical studies related to health, ethical and social issues in field of Preventive Medicine. Articles with clinical interest and implications will be given preference.