Thymoquinone Attenuates Retinal Expression of Mediators and Markers of Neurodegeneration in a Diabetic Animal Model.

IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Khalid M Alkharfy, Ajaz Ahmad, Mohammad Mairaj Siddiquei, Mohammad Ghulam, Ahmed Abu El-Asrar
{"title":"Thymoquinone Attenuates Retinal Expression of Mediators and Markers of Neurodegeneration in a Diabetic Animal Model.","authors":"Khalid M Alkharfy,&nbsp;Ajaz Ahmad,&nbsp;Mohammad Mairaj Siddiquei,&nbsp;Mohammad Ghulam,&nbsp;Ahmed Abu El-Asrar","doi":"10.2174/1874467215666220113105300","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Diabetic retinopathy (DR) is a slow eye disease that affects the retina due to a long-standing uncontrolled diabetes mellitus. Hyperglycemia-induced oxidative stress can lead to neuronal damage leading to DR.</p><p><strong>Objective: </strong>The aim of the current investigation is to assess the protective effects of thymoquinone (TQ) as a potential compound for the treatment and/or prevention of neurovascular complications of diabetes, including DR.</p><p><strong>Methods: </strong>Diabetes was induced in rats by the administration of streptozotocin (55 mg/kg intraperitoneally, i.p.). Subsequently, diabetic rats were treated with either TQ (2 mg/kg i.p.) or vehicle on alternate days for three weeks. A healthy control group was also run in parallel. At the end of the treatment period, animals were euthanized, and the retinas were collected and analyzed for the expression levels of brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH), nerve growth factor receptor (NGFR), and caspase-3 using Western blotting techniques in the retina of diabetic rats and compared with the normal control rats. In addition, dichlorofluorescein (DCF) levels in the retina were assessed as a marker of reactive oxygen species (ROS), and blood-retinal barrier breakdown (BRB) was examined for vascular permeability. The systemic effects of TQ treatments on glycemic control, kidney and liver functions were also assessed in all groups.</p><p><strong>Results: </strong>Diabetic animals treated with TQ showed improvements in the liver and kidney functions compared with control diabetic rats. Normalization in the levels of neuroprotective factors, including BDNF, TH, and NGFR, was observed in the retina of diabetic rats treated with TQ. In addition, TQ ameliorated the levels of apoptosis regulatory protein caspase-3 in the retina of diabetic rats and reduced disruption of the blood-retinal barrier, possibly through a reduction in reactive oxygen species (ROS) generation.</p><p><strong>Conclusion: </strong>These findings suggest that TQ harbors a significant potential to limit the neurodegeneration and retinal damage that can be provoked by hyperglycemia in vivo.</p>","PeriodicalId":10865,"journal":{"name":"Current molecular pharmacology","volume":null,"pages":null},"PeriodicalIF":2.4000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current molecular pharmacology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.2174/1874467215666220113105300","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 4

Abstract

Background: Diabetic retinopathy (DR) is a slow eye disease that affects the retina due to a long-standing uncontrolled diabetes mellitus. Hyperglycemia-induced oxidative stress can lead to neuronal damage leading to DR.

Objective: The aim of the current investigation is to assess the protective effects of thymoquinone (TQ) as a potential compound for the treatment and/or prevention of neurovascular complications of diabetes, including DR.

Methods: Diabetes was induced in rats by the administration of streptozotocin (55 mg/kg intraperitoneally, i.p.). Subsequently, diabetic rats were treated with either TQ (2 mg/kg i.p.) or vehicle on alternate days for three weeks. A healthy control group was also run in parallel. At the end of the treatment period, animals were euthanized, and the retinas were collected and analyzed for the expression levels of brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH), nerve growth factor receptor (NGFR), and caspase-3 using Western blotting techniques in the retina of diabetic rats and compared with the normal control rats. In addition, dichlorofluorescein (DCF) levels in the retina were assessed as a marker of reactive oxygen species (ROS), and blood-retinal barrier breakdown (BRB) was examined for vascular permeability. The systemic effects of TQ treatments on glycemic control, kidney and liver functions were also assessed in all groups.

Results: Diabetic animals treated with TQ showed improvements in the liver and kidney functions compared with control diabetic rats. Normalization in the levels of neuroprotective factors, including BDNF, TH, and NGFR, was observed in the retina of diabetic rats treated with TQ. In addition, TQ ameliorated the levels of apoptosis regulatory protein caspase-3 in the retina of diabetic rats and reduced disruption of the blood-retinal barrier, possibly through a reduction in reactive oxygen species (ROS) generation.

Conclusion: These findings suggest that TQ harbors a significant potential to limit the neurodegeneration and retinal damage that can be provoked by hyperglycemia in vivo.

百里醌减弱糖尿病动物模型中神经变性介质和标志物的视网膜表达。
背景:糖尿病视网膜病变(DR)是一种慢性眼病,由于长期不受控制的糖尿病而影响视网膜。目的:评价百里醌(TQ)作为一种治疗和/或预防糖尿病(包括糖尿病)神经血管并发症的潜在化合物的保护作用。方法:采用链脲佐菌素(55 mg/kg,腹腔注射)诱导大鼠糖尿病。随后,糖尿病大鼠隔日给予TQ (2 mg/kg i.p.)或载药治疗,连续3周。一个健康的对照组也在平行进行。治疗期结束后,取动物视网膜,采用Western blotting技术分析糖尿病大鼠视网膜中脑源性神经营养因子(BDNF)、酪氨酸羟化酶(TH)、神经生长因子受体(NGFR)、caspase-3的表达水平,并与正常对照大鼠进行比较。此外,评估视网膜中的二氯荧光素(DCF)水平作为活性氧(ROS)的标志物,并检查血视网膜屏障破裂(BRB)的血管通透性。还评估了TQ治疗对各组血糖控制、肾功能和肝功能的全身影响。结果:与对照组糖尿病大鼠相比,经TQ治疗的糖尿病大鼠肝肾功能明显改善。经TQ治疗的糖尿病大鼠视网膜中神经保护因子(包括BDNF、TH和NGFR)水平恢复正常。此外,TQ改善了糖尿病大鼠视网膜中凋亡调节蛋白caspase-3的水平,减少了血视网膜屏障的破坏,可能是通过减少活性氧(ROS)的产生。结论:这些研究结果表明,TQ对体内高血糖引起的神经变性和视网膜损伤具有重要的抑制作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Current molecular pharmacology
Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery
CiteScore
4.90
自引率
3.70%
发文量
112
期刊介绍: Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信