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氧化应激诱导的抗氧化和神经毒性在体内斑马鱼胚胎或幼体模型中得到证实,而桑色素使其恢复正常,显示出治疗意义。

Oxidative stress induced antioxidant and neurotoxicity demonstrated in vivo zebrafish embryo or larval model and their normalization due to morin showing therapeutic implications.

作者信息

Issac Praveen Kumar, Guru Ajay, Velayutham Manikandan, Pachaiappan Raman, Arasu Mariadhas Valan, Al-Dhabi Naif Abdullah, Choi Ki Choon, Harikrishnan Ramasamy, Arockiaraj Jesu

机构信息

SRM Research Institute, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India.

SRM Research Institute, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India; Department of Biotechnology, College of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, 603 203 Chennai, Tamil Nadu, India.

出版信息

Life Sci. 2021 Oct 15;283:119864. doi: 10.1016/j.lfs.2021.119864. Epub 2021 Aug 3.

DOI:10.1016/j.lfs.2021.119864
PMID:34358548
Abstract

AIMS

The study examined that morin as possible antioxidant and neuroprotective due to oxidative stress (HO) in zebrafish larval model.

MATERIALS AND METHODS

Zebrafish larvae were induced with oxidative stress using HO at 1 mM; their behavioural changes were assessed through partition preference and horizontal compartment test. The head section without eyes and yolk sac of zebrafish larvae were employed for enzyme assays such as SOD, CAT, Thiobarbituric acid reactive substances assay, reduced glutathione, glutathione peroxidase activity, glutathione S transferase, Acetylcholinesterase activity and nitrate levels. Also, intracellular ROS and apoptosis in larval head was detected by DCFDA and acridine orange staining followed by gene expression studies.

KEY FINDINGS

Morin exposure was not harmful to the larvae at concentration between 20 and 60 μM, but it caused non-lethal deformity between 80 and 100 μM. In the partition test, zebrafish embryos treated with HO showed cognitive impairment, whereas the morin-treated groups showed an improved behavioural activity. The study also found that restoring antioxidant enzymes and reduced lipid peroxidation which had a neuroprotective impact. Inhibition of NO overproduction and increased AChE activity were also shown to reduce the neuronal damage. Apoptosis and intracellular ROS levels were reduced in larvae when it was co-incubated with morin. Morin treatment up regulated the antioxidant enzymes against oxidative stress.

SIGNIFICANCE

Morin provides protection against HO induced oxidative stress through a cellular antioxidant defence mechanism by up-regulating gene expression, thus increasing the antioxidant activity at cellular or organismal stage.

摘要

目的

本研究在斑马鱼幼体模型中检测了桑色素作为一种可能的抗氧化剂和神经保护剂对氧化应激(HO)的作用。

材料与方法

使用1 mM的HO诱导斑马鱼幼体产生氧化应激;通过分区偏好和水平隔室试验评估其行为变化。使用斑马鱼幼体无眼和卵黄囊的头部进行酶活性检测,如超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、硫代巴比妥酸反应物质检测、还原型谷胱甘肽、谷胱甘肽过氧化物酶活性、谷胱甘肽S转移酶、乙酰胆碱酯酶活性和硝酸盐水平检测。此外,通过2',7'-二氯二氢荧光素二乙酸酯(DCFDA)和吖啶橙染色检测幼体头部的细胞内活性氧(ROS)和细胞凋亡,随后进行基因表达研究。

主要发现

在20至60 μM浓度范围内,桑色素暴露对幼体无害,但在80至100 μM浓度时会导致非致命性畸形。在分区试验中,用HO处理的斑马鱼胚胎表现出认知障碍,而用桑色素处理的组表现出行为活性改善。研究还发现,桑色素可恢复抗氧化酶活性并减少脂质过氧化,具有神经保护作用。抑制一氧化氮(NO)过量产生和增加乙酰胆碱酯酶(AChE)活性也可减少神经元损伤。与桑色素共同孵育时,幼体中的细胞凋亡和细胞内ROS水平降低。桑色素处理上调了抗氧化酶以抵抗氧化应激。

意义

桑色素通过上调基因表达,通过细胞抗氧化防御机制提供针对HO诱导的氧化应激的保护,从而在细胞或机体阶段增加抗氧化活性。

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