槲皮素及载槲皮素壳聚糖纳米粒通过减轻氧化应激、炎症和细胞凋亡对顺铂诱导的肾毒性和睾丸毒性的疗效。

Efficacy of Quercetin and Quercetin Loaded Chitosan Nanoparticles Against Cisplatin-Induced Renal and Testicular Toxicity via Attenuation of Oxidative Stress, Inflammation, and Apoptosis.

作者信息

Bakr Alaa F, El-Shiekh Riham A, Mahmoud Mohamed Y, Khalil Heba M A, Alyami Mohammad H, Alyami Hamad S, Galal Omneya, Mansour Dina F

机构信息

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.

Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.

出版信息

Pharmaceuticals (Basel). 2024 Oct 17;17(10):1384. doi: 10.3390/ph17101384.

DOI:10.3390/ph17101384

PMID:39459023

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11510010/

Abstract

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.

摘要

背景/目的：包括槲皮素在内的黄酮类化合物因其潜在的健康促进作用而备受关注。

方法

当前实验旨在观察纳米颗粒形式的槲皮素（QUE）是否比常规制剂的QUE更有效地减轻顺铂（CIS）引起的睾丸和肾脏毒性。将大鼠随机单独用CIS或与QUE或QUE.NPs（载槲皮素壳聚糖纳米颗粒）联合处理4周。QUE和QUE.NPs经口给予（10mg/kg，每周三次），而CIS经腹腔给予（2mg/kg，每周两次）。

结果

与QUE和CIS + QUE.NP处理的大鼠相比，CIS暴露诱导焦虑和情绪应激，并促进睾丸和肾脏组织中的氧化应激。此外，CIS降低血清睾酮水平，减少睾丸IL-10，以及CIS诱导的肾衰竭，表现为低钾血症，以及肌酐、尿素、钠、IL-18和KIM-1水平升高。此外，在CIS中毒大鼠的睾丸和肾脏中观察到严重的组织学变化。关于免疫组织化学染色，CIS显著上调Bax，下调Bcl-2，并适度增强PCNA表达。