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载橄榄苦苷的银纳米粒子通过调控内质网应激和细胞凋亡减轻阿霉素诱导的睾丸损伤。

Silver Nanoparticles Loaded with Oleuropein Reduce Doxorubicin-Induced Testicular Damage by Regulating Endoplasmic Reticulum Stress, and Apoptosis.

机构信息

Department of Histology and Embryology, Faculty of Veterinary Medicine, Atatürk University, Erzurum, Turkey.

Department of Physiology, Faculty of Veterinary Medicine, Kafkas University, Kars, Turkey.

出版信息

Biol Trace Elem Res. 2024 Oct;202(10):4687-4698. doi: 10.1007/s12011-024-04058-y. Epub 2024 Jan 10.

DOI:10.1007/s12011-024-04058-y
PMID:38197904
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11339148/
Abstract

Doxorubicin (DOX) is the most used chemotherapeutic agent for treating solid tumors. DOX treatment may lead to testicular damage using oxidative stress, resulting in infertility. These adverse effects may be prevented by the activation of antioxidant systems. Oleuropein (OLE) is a powerful flavonoid with several ameliorative effects, including antioxidative, antiproliferative, and anti-inflammatory. It would be more efficient and applicable in treating chronic human diseases if its poor bioavailability improves with a nano-delivery system. The current study aims to assess the histopathological changes and antioxidative effects of OLE loaded with silver nanoparticles oleuropein (OLE-AgNP) on the testicular injury triggered by DOX in rats. Forty-eight male albino rats were randomly divided into six groups as follows: the control, DOX (2.5 mg/kg), OLE (50 mg/kg), AgNP (100 mg/kg), OLE + AgNP (50 mg/kg), OLE (50 mg/kg) + DOX (2.5 mg/kg), AgNP (100 mg/kg) + DOX (2.5 mg/kg), and OLE-AgNP (50 mg/kg) + DOX (2.5 mg/kg) for 11 days. Oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress markers, sperm analysis, and histopathological analyses were performed on testicular tissues taken from rats decapitated after the applications and compared between the experimental groups. The tissue MDA level was lower in the OLE and OLE+AgNP-treated groups than in the DOX-treated group. In addition, SOD and GSH levels significantly increased in both the OLE and OLE+AgNP-treated groups compared to the DOX group. Both OLE and OLE+AgNP, particularly OLE+AgNP, ameliorated DOX-induced testicular tissue injury, as evidenced by reduced injury and improved seminiferous tubules and spermatocyte area. In addition, OLE and OLE+AgNP, especially OLE+AgNP, inhibited DOX-induced testicular tissue inflammation, apoptosis, and endoplasmic reticulum stress. The findings suggest that nanotechnology and the production of OLE+AgNP can ameliorate DOX-induced testicular damage.

摘要

多柔比星(DOX)是治疗实体瘤最常用的化疗药物。DOX 治疗可能会导致睾丸损伤,引发氧化应激,导致不孕。这些不良反应可以通过激活抗氧化系统来预防。橄榄苦苷(OLE)是一种具有多种改善作用的强大类黄酮,包括抗氧化、抗增殖和抗炎作用。如果其较差的生物利用度通过纳米递药系统得到改善,它将更有效且适用于治疗慢性人类疾病。本研究旨在评估负载银纳米粒子的橄榄苦苷(OLE-AgNP)对 DOX 诱导的大鼠睾丸损伤的组织病理学变化和抗氧化作用。48 只雄性白化大鼠随机分为六组:对照组、DOX(2.5mg/kg)组、OLE(50mg/kg)组、AgNP(100mg/kg)组、OLE+AgNP(50mg/kg)组、OLE(50mg/kg)+DOX(2.5mg/kg)组、AgNP(100mg/kg)+DOX(2.5mg/kg)组和 OLE-AgNP(50mg/kg)+DOX(2.5mg/kg)组,共 11 天。对断头处死大鼠的睾丸组织进行氧化应激、炎症、凋亡、内质网应激标志物、精子分析和组织病理学分析,并与实验组进行比较。与 DOX 处理组相比,OLE 和 OLE+AgNP 处理组的组织 MDA 水平较低。此外,OLE 和 OLE+AgNP 处理组的 SOD 和 GSH 水平均显著高于 DOX 组。OLE 和 OLE+AgNP,特别是 OLE+AgNP,改善了 DOX 诱导的睾丸组织损伤,表现为损伤减轻,生精小管和精母细胞面积改善。此外,OLE 和 OLE+AgNP,特别是 OLE+AgNP,抑制了 DOX 诱导的睾丸组织炎症、凋亡和内质网应激。这些发现表明,纳米技术和 OLE+AgNP 的生产可以改善 DOX 诱导的睾丸损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aab8/11339148/cae4c74da368/12011_2024_4058_Fig5_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aab8/11339148/cae4c74da368/12011_2024_4058_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aab8/11339148/9737a2af6f26/12011_2024_4058_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aab8/11339148/fca4a6ea4a54/12011_2024_4058_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aab8/11339148/65b36564255a/12011_2024_4058_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aab8/11339148/6a2a15185560/12011_2024_4058_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aab8/11339148/cae4c74da368/12011_2024_4058_Fig5_HTML.jpg

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