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阿久哇枣对阿霉素诱导的肾毒性大鼠的植物化学分析及肾保护潜力:生化和分子对接方法

Phytochemical analysis and nephroprotective potential of Ajwa date in doxorubicin-induced nephrotoxicity rats: Biochemical and molecular docking approaches.

作者信息

Baothman Othman A S, Altayb Hisham N, Zeyadi Mustafa A, Hosawi Salman B, Abo-Golayel Mohamed Kamel

机构信息

Biochemistry Department, Faculty of Science King Abdulaziz University Jeddah Saudi Arabia.

Microbial Toxicology & Natural Products Center, Faculty of Science King Abdulaziz University Jeddah Saudi Arabia.

出版信息

Food Sci Nutr. 2023 Jan 27;11(3):1584-1598. doi: 10.1002/fsn3.3199. eCollection 2023 Mar.

Abstract

The purpose of this study is to evaluate the likely defensive impact of Ajwa date aqueous extract (AJDAE) in alleviating the nephrotoxicity generated by doxorubicin (DOX) injection in rats. Sixty male Wister albino rats were randomly and equally separated into six groups ( = 10), and they were treated as follows: untreated control group, extract groups administered with 0.75 and 1.5 mg kg bw of AJDAE, toxicant control group administered with DOX, and prophylactic groups were treated with 0.75 and 1.5 mg/kg of AJDAE and 15 mg/kg DOX. Biochemical parameters, antioxidant enzymes, renal functions, DNA integrity, and histopathology were studied to evaluate the nephroprotective activity of AJDAE. Furthermore, bioactive compounds were utilized for in silico molecular docking. AJDAE treatment resulted in significant improvements in the amended renal biomarkers (urea, creatinine, calcium, phosphorous, and uric acid), antioxidative markers, and MDA. Noticeable histopathological improvements supported this result. Results of in silico studies revealed that d-Mannitol, 6TMS derivative, palmitic acid, and TMS derivative had a higher docking score with human soluble epoxide hydrolase (-10.9 kcal/mol) and NF-κB-DNA (-7 kcal/mol). The present findings indicated that AJDAE could decrease ROS generation and lipid peroxidation (LPO) and repair the DOX injection-related DNA damage.

摘要

本研究的目的是评估阿久哇枣水提取物(AJDAE)对减轻大鼠注射阿霉素(DOX)所产生的肾毒性可能具有的防御作用。将60只雄性Wister白化大鼠随机且平均分为六组(每组 = 10只),并进行如下处理:未处理的对照组、给予0.75和1.5 mg/kg体重AJDAE的提取物组、给予DOX的毒性对照组,以及给予0.75和1.5 mg/kg的AJDAE及15 mg/kg DOX的预防组。研究了生化参数、抗氧化酶、肾功能、DNA完整性和组织病理学,以评估AJDAE的肾保护活性。此外,利用生物活性化合物进行计算机模拟分子对接。AJDAE处理使修正后的肾脏生物标志物(尿素、肌酐、钙、磷和尿酸)、抗氧化标志物和丙二醛有显著改善。明显的组织病理学改善支持了这一结果。计算机模拟研究结果显示,d-甘露醇、6TMS衍生物、棕榈酸和TMS衍生物与人可溶性环氧化物水解酶(-10.9 kcal/mol)和NF-κB-DNA(-7 kcal/mol)具有更高的对接分数。目前的研究结果表明,AJDAE可以减少活性氧生成和脂质过氧化(LPO),并修复与DOX注射相关的DNA损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f5a/10002938/9517208e1ebe/FSN3-11-1584-g020.jpg

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