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姜黄素减轻马拉硫磷诱导的肾损伤:抑制细胞凋亡以及调节NF-κβ/TNF-α和Nrf2及HO-1信号通路

Curcumin Mitigates Malathion-Induced Renal Injury: Suppression of Apoptosis and Modulation of NF-κβ/TNF-α and Nrf2, and HO-1 Signaling.

作者信息

Eldesoqui Mamdouh, Ahmed Magda E, Abdel-Kareem Mona A, Badawy Mohamed Moharram, Dawood Amal Fahmy, Mohamed Abdelaty Shawky, Ibrahim Ateya Megahed, El-Mansi Ahmed A, El-Sherbiny Mohamad, Hendawy Mahmoud

机构信息

Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.

Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia.

出版信息

Metabolites. 2023 Oct 30;13(11):1117. doi: 10.3390/metabo13111117.

DOI:10.3390/metabo13111117
PMID:37999213
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10673029/
Abstract

Malathion is one of the most used organophosphorus pesticides that is used for many reasons such as agriculture and industry. Human exposure to malathion may occur through various means, such as eating food that has been treated with it. Malathion not only increases oxidative stress but also decreases the antioxidant capacity. Curcumin is a powerful antioxidant with many pharmacological actions. Curcumin can act as a free radical scavenger and inhibit the activation and nuclear translocation of NF-κB. Curcumin could combat the lipid peroxidation and antioxidant depletion that trigger the apoptotic pathways. This study aims to examine the antioxidant, anti-inflammatory, and antiapoptotic effects of curcumin. Twenty-four Sprague Dawley rats were divided into four groups (six rats each): control, curcumin, malathion, and malathion + curcumin groups. At the assigned time, blood samples were used for the assessment of serum creatinine, and the kidneys were excised and washed; parts of them were used for the assessment of total oxidant status (TOS), oxidative stress index (OSI), the oxidative stress marker malondialdehyde (MDA), total antioxidant capacity (TAC), and glutathione (GSH) activity, other parts were fixed in formalin for further staining. Histopathological evaluation was performed for the fixed specimens after staining with H&E, sirus red, and the immunohistochemical staining for NF-κβ, TNF-α, Caspase-3, Nrf2, and HO-1. Curcumin significantly decreases the serum creatinine after malathion exposure and significantly restores the oxidant/antioxidant balance by increasing TAC and GSH and decreasing TOS, OSI, and MDA. Curcumin exerts its reno-protective effect and restores the histological architecture of the kidney by downregulating the immune expression of NF-κβ, TNF-α, and Caspase-3 and upregulating the expression of Nrf2 and HO-1. This study concluded that curcumin protects against nephrotoxicity caused by malathion by exerting its antioxidant, anti-inflammatory, and anti-apoptotic capabilities.

摘要

马拉硫磷是最常用的有机磷农药之一,因其在农业和工业等诸多领域的用途而被广泛使用。人类接触马拉硫磷可能通过多种途径发生,比如食用经过其处理的食物。马拉硫磷不仅会增加氧化应激,还会降低抗氧化能力。姜黄素是一种具有多种药理作用的强大抗氧化剂。姜黄素可以作为自由基清除剂,抑制核因子κB(NF-κB)的激活和核转位。姜黄素能够对抗引发凋亡途径的脂质过氧化和抗氧化剂耗竭。本研究旨在探讨姜黄素的抗氧化、抗炎和抗凋亡作用。将24只斯普拉格-道利大鼠分为四组(每组6只):对照组、姜黄素组、马拉硫磷组和马拉硫磷+姜黄素组。在指定时间,采集血样用于评估血清肌酐,切除肾脏并冲洗;部分肾脏用于评估总氧化剂状态(TOS)、氧化应激指数(OSI)、氧化应激标志物丙二醛(MDA)、总抗氧化能力(TAC)和谷胱甘肽(GSH)活性,其他部分用福尔马林固定以进行进一步染色。对用苏木精-伊红(H&E)、天狼星红染色以及对NF-κβ、肿瘤坏死因子-α(TNF-α)、半胱天冬酶-3(Caspase-3)、核因子E2相关因子-(Nrf2)和血红素加氧酶-1(HO-1)进行免疫组化染色后的固定标本进行组织病理学评估。姜黄素在马拉硫磷暴露后显著降低血清肌酐,并通过增加TAC和GSH以及降低TOS、OSI和MDA,显著恢复氧化/抗氧化平衡。姜黄素通过下调NF-κβ、TNF-α和Caspase-3的免疫表达以及上调Nrf2和HO-1的表达,发挥其肾脏保护作用并恢复肾脏的组织结构。本研究得出结论,姜黄素通过发挥其抗氧化、抗炎和抗凋亡能力,对马拉硫磷引起的肾毒性具有保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5248/10673029/efaad77e748c/metabolites-13-01117-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5248/10673029/93d694e26181/metabolites-13-01117-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5248/10673029/efaad77e748c/metabolites-13-01117-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5248/10673029/6e2eaf13242e/metabolites-13-01117-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5248/10673029/2630cc3ad5b1/metabolites-13-01117-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5248/10673029/5b61956ee3d8/metabolites-13-01117-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5248/10673029/93d694e26181/metabolites-13-01117-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5248/10673029/efaad77e748c/metabolites-13-01117-g007.jpg

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