槲皮素和槲皮素负载壳聚糖纳米颗粒通过减轻氧化应激、炎症和细胞凋亡对顺铂诱导的肾脏和睾丸毒性的疗效

IF 4.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Pharmaceuticals Pub Date : 2024-10-17 DOI:10.3390/ph17101384
Alaa F Bakr, Riham A El-Shiekh, Mohamed Y Mahmoud, Heba M A Khalil, Mohammad H Alyami, Hamad S Alyami, Omneya Galal, Dina F Mansour
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引用次数: 0

摘要

背景/目的:黄酮类化合物,包括槲皮素,因其潜在的促进健康的作用而备受关注:本实验旨在研究纳米颗粒形式的槲皮素(QUE)能否比普通配方的QUE更有效地减轻顺铂(CIS)引起的睾丸和肾毒性。大鼠随机接受 CIS 单独或与 QUE 或 QUE.NPs (槲皮素载壳聚糖纳米颗粒)联合治疗 4 周。QUE和QUE.NPs口服(10毫克/千克,每周三次),CIS腹腔注射(2毫克/千克,每周两次):结果:与QUE和CIS + QUE.NP处理的大鼠相比,CIS会诱发焦虑和情绪应激,并促进睾丸和肾组织的氧化应激。此外,CIS还降低了血清睾酮水平,减少了睾丸的IL-10,并导致肾功能衰竭,表现为低钾血症,肌酐、尿素、钠、IL-18和KIM-1水平升高。此外,还观察到 CIS 中毒大鼠的睾丸和肾脏发生了严重的组织学变化。在免疫组化染色方面,CIS 能显著上调 Bax,下调 Bcl-2,并适度增强 PCNA 的表达:我们的研究结果表明,QUE 和 QUE.NPs 都能调节情绪紊乱,并通过调节氧化、炎症和细胞凋亡改善睾丸和肾功能。然而,QUE.NPs 比 QUE 处理的大鼠表现更好。
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Efficacy of Quercetin and Quercetin Loaded Chitosan Nanoparticles Against Cisplatin-Induced Renal and Testicular Toxicity via Attenuation of Oxidative Stress, Inflammation, and Apoptosis.

Background/objectives: Flavonoids, including quercetin, have attracted much attention due to their potential health-promoting effects.

Methods: The current experiment aims to see whether quercetin (QUE) in nanoparticle form could mitigate testicular and renal toxicity caused by cisplatin (CIS) more effectively than normally formulated QUE. Rats were randomly treated with CIS alone or in combination with QUE or QUE.NPs (Quercetin-loaded chitosan nanoparticles) for 4 weeks. QUE and QUE.NPs were given orally (10 mg/kg, three times a week), while CIS was given intraperitoneally (2 mg/kg, twice a week).

Results: Compared to QUE- and CIS + QUE.NP-treated rats, CIS exposure induced anxiety and emotional stress as well as promoted oxidative stress in both testicular and renal tissues. Moreover, CIS reduced serum testosterone levels and diminished testicular IL-10, as well as CIS-induced renal failure, as indicated by hypokalemia, and increased levels of creatinine, urea, sodium, IL-18, and KIM-1. Further, severe histological changes were observed in the testis and kidney of CIS-intoxicated rats. Regarding immunohistochemical staining, CIS significantly upregulated Bax, downregulated Bcl-2, and moderately enhanced PCNA expression.

Conclusions: Our findings suggest that both QUE and QUE.NPs modulated emotional disturbance and improved testicular and renal functions via modulation of oxidation, inflammation, and apoptosis. However, QUE.NPs performed better than QUE-treated rats.

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来源期刊
Pharmaceuticals
Pharmaceuticals Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.10
自引率
4.30%
发文量
1332
审稿时长
6 weeks
期刊介绍: Pharmaceuticals (ISSN 1424-8247) is an international scientific journal of medicinal chemistry and related drug sciences.Our aim is to publish updated reviews as well as research articles with comprehensive theoretical and experimental details. Short communications are also accepted; therefore, there is no restriction on the maximum length of the papers.
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