Neuroprotective potential of solanesol against tramadol induced zebrafish model of Parkinson's disease: insights from neurobehavioral, molecular, and neurochemical evidence.

IF 2.1 4区 医学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Drug and Chemical Toxicology Pub Date : 2024-11-01 Epub Date: 2024-06-28 DOI:10.1080/01480545.2024.2355542
Md Reyaz Alam, Vaishali Dobhal, Shamsher Singh
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Abstract

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and subsequent depletion of dopamine in the striatum. Solanesol, an alcohol that acts as a precursor to coenzyme Q10, possesses potential applications in managing neurological disorders with antioxidant, anti-inflammatory, and neuromodulatory potential. In this study, a zebrafish model was employed to investigate the effects of solanesol in tramadol induced PD like symptoms. Zebrafish were administered tramadol injections (50 mg/kg) over a 20-day period. Solanesol was administered at doses of 25, 50, and 100 mg/kg, three hours prior to tramadol administration from day 11 to day 20. Behavioral tests assessing motor coordination were conducted on a weekly basis using open field and novel diving tank apparatus. On day 21, the zebrafish were euthanized, and brain tissues were examined for markers of oxidative stress, inflammation, and neurotransmitters level. Chronic tramadol treatment resulted in motor impairment, reduced antioxidant enzyme levels, enhanced release of proinflammatory cytokines in the striatum, and disrupted neurotransmitter balance. However, solanesol administration mitigated these effects and exhibited a neuroprotective effect against neurodegenerative alterations in the zebrafish model of PD. This was evident through improvements in behavior, modulation of biochemical markers, attenuation of neuroinflammation, restoration of neurotransmitters level, and enhancement of mitochondrial activity. The histopathological study also confirmed that solanesol dose dependently restored neuronal cell density which confirmed its neuroprotective potential. Further investigations are required to elucidate the underlying mechanisms of solanesol neuroprotective effects and evaluate its efficacy in human patients.

独活素对曲马多诱导的帕金森病斑马鱼模型的神经保护潜力:神经行为、分子和神经化学证据的启示。
帕金森病(Parkinson's disease,PD)是一种常见的神经退行性疾病,其特征是黑质髓鞘(substantia nigra pars compacta,SNpc)中多巴胺能神经元的丧失以及随后纹状体中多巴胺的耗竭。茄红素是一种可作为辅酶 Q10 前体的酒精,具有抗氧化、抗炎和神经调节潜力,可用于治疗神经系统疾病。本研究采用斑马鱼模型来研究 Solanesol 对曲马多诱发的类似帕金森病症状的影响。给斑马鱼注射曲马多(50 毫克/千克),为期 20 天。从第11天到第20天,在曲马多给药前三小时,分别以25、50和100毫克/千克的剂量给斑马鱼注射索拉尼索尔。每周使用露天场地和新型潜水槽装置进行行为测试,评估运动协调性。第21天,斑马鱼被安乐死,脑组织接受氧化应激标记物、炎症和神经递质水平检查。长期曲马多治疗会导致斑马鱼运动障碍、抗氧化酶水平降低、纹状体中促炎细胞因子释放增加以及神经递质平衡紊乱。然而,服用 Solanesol 可减轻这些影响,并对斑马鱼脑退化症模型的神经退行性改变起到保护作用。这表现在行为的改善、生化指标的调节、神经炎症的减轻、神经递质水平的恢复以及线粒体活性的增强。组织病理学研究还证实,solanesol 的剂量依赖性可恢复神经细胞密度,这证实了其神经保护潜力。要阐明solanesol神经保护作用的内在机制并评估其对人类患者的疗效,还需要进一步的研究。
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来源期刊
Drug and Chemical Toxicology
Drug and Chemical Toxicology 医学-毒理学
CiteScore
6.00
自引率
3.80%
发文量
99
审稿时长
3 months
期刊介绍: Drug and Chemical Toxicology publishes full-length research papers, review articles and short communications that encompass a broad spectrum of toxicological data surrounding risk assessment and harmful exposure. Manuscripts are considered according to their relevance to the journal. Topics include both descriptive and mechanics research that illustrates the risk assessment implications of exposure to toxic agents. Examples of suitable topics include toxicological studies, which are structural examinations on the effects of dose, metabolism, and statistical or mechanism-based approaches to risk assessment. New findings and methods, along with safety evaluations, are also acceptable. Special issues may be reserved to publish symposium summaries, reviews in toxicology, and overviews of the practical interpretation and application of toxicological data.
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