Vitamin D and canagliflozin combination alleviates Parkinson's disease in rats through modulation of RAC1/NF-κB/Nrf2 interaction.

IF 2.9 4区 医学 Q3 IMMUNOLOGY
Sara Kamal Rizk, Eman A Ali, AlZahraa A M Sheref, Sara G Tayel, Sara A El Derbaly
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引用次数: 0

Abstract

Objective: Oxidative stress and neuroinflammation are crucial factors in the pathogenesis of Parkinson's disease (PD). Vitamin D (Vit D) and canagliflozin (CAN) are known to have anti-inflammatory and antioxidant properties. Together, they target key molecular pathways involved in PD, including oxidative stress and neuroinflammation, specifically, the small GTPase protein (RAC1)/nuclear factor-kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, which regulates brain's oxidative stress and inflammation. This study investigates the effects of Vit D and CAN alone and in combination in a rat model of PD.

Materials and methods: Fifty male Wistar rats were assigned to five groups (n = 10), including control, rotenone (ROT), Vit D + ROT, CAN + ROT, and Vit D + CAN + ROT. We assessed weight changes, brain weight, neurobehavioral functions, biochemical markers, and immunohistopathology of brain tissues.

Results: The results showed that Vit D treatment was more effective than CAN in alleviating PD symptoms, with the combination of Vit D and CAN offering the best therapeutic outcome. This combination therapy significantly improved serum Vit D, striatal dopamine (DA) levels, antioxidant status (reduced glutathione (GSH) and catalase (CAT), reduced oxidative stress (malondialdehyde (MDA)), and ameliorated inflammation (tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 10 (IL-10)). Additionally, the combination therapy modulated the expression of RAC1, NF-κB, Nrf2, vitamin D receptors (VDR), and vitamin D-binding protein (DBP) and immunoexpression of tyrosine hydroxylase (TH), and α-synuclein (α-SYN).

Conclusion: These findings suggest that Vit D and CAN synergistically modulate the RAC1/NF-κB/Nrf2 pathway, leading to improved neuroprotection in PD.

维生素D与卡格列净联用通过调节RAC1/NF-κB/Nrf2相互作用缓解大鼠帕金森病。
目的:氧化应激和神经炎症是帕金森病(PD)发病的关键因素。众所周知,维生素D (Vit D)和卡格列净(CAN)具有抗炎和抗氧化的特性。它们共同靶向PD参与的关键分子通路,包括氧化应激和神经炎症,特别是调节脑氧化应激和炎症的小GTPase蛋白(RAC1)/核因子κB (NF-κB)/核因子红细胞2相关因子2 (Nrf2)信号。本研究探讨了Vit D和CAN单独及联合使用对帕金森病大鼠模型的影响。材料与方法:雄性Wistar大鼠50只,随机分为对照组、鱼藤酮(ROT)组、Vit D + ROT组、CAN + ROT组、Vit D + CAN + ROT组5组(n = 10)。我们评估了体重变化、脑重量、神经行为功能、生化指标和脑组织免疫组织病理学。结果:Vit D治疗对PD症状的缓解效果优于CAN,其中Vit D与CAN合用治疗效果最佳。这种联合治疗显著改善血清Vit D、纹状体多巴胺(DA)水平、抗氧化状态(还原谷胱甘肽(GSH)和过氧化氢酶(CAT))、氧化应激(丙二醛(MDA))和炎症(肿瘤坏死因子-α (TNF-α)、白细胞介素6 (IL-6)和白细胞介素10 (IL-10))。此外,联合治疗还调节了RAC1、NF-κB、Nrf2、维生素D受体(VDR)、维生素D结合蛋白(DBP)的表达以及酪氨酸羟化酶(TH)、α-突触核蛋白(α-SYN)的免疫表达。结论:Vit D和CAN协同调节RAC1/NF-κB/Nrf2通路,增强PD患者的神经保护作用。
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来源期刊
CiteScore
5.40
自引率
0.00%
发文量
133
审稿时长
4-8 weeks
期刊介绍: The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).
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