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载乳铁蛋白硒纳米粒对博来霉素诱导肝损伤的肝和免疫调节作用。

Hepatic and immune modulatory effectiveness of lactoferrin loaded Selenium nanoparticles on bleomycin induced hepatic injury.

机构信息

Medical Physiology Department, National Research Centre, Giza, 12622, Egypt.

Zoology Department, Faculty of Science, Al-Azhar University, Assuit, Egypt.

出版信息

Sci Rep. 2024 Sep 10;14(1):21066. doi: 10.1038/s41598-024-70894-6.

Abstract

This study aimed to estimate the hepatic and immune ameliorating potential of extracted bovine lactoferrin (LF), Selenium nanoparticles (SeNPs) or their combination (LF/SeNPs) against bleomycin (BLM) induced hepatic injury. Fifty adult male rats (160-200 g) were equally divided into five groups: (1) the saline control group, (2) BLM-injected (15 mg/kg twice a week, ip), and (3-5) groups treated orally with LF (200 mg/kg/day), SeNPs (0.0486 mg/kg/day) or LF/SeNPs combination (200.0486 mg/kg/day) for 6 weeks post BLM-intoxication. Blood and liver samples were subjected to biochemical, histopathological, and immunohistochemical analyses. The results revealed that BLM caused a significant increase in hepatic lipid peroxidation and nitric oxide, as well as serum markers of liver functions (AST, ALT and GGT activities), and levels of GM-CSF, CD4, TNF-α, IL-1β, TGF-β1, fibronectin, triglycerides, cholesterol and LDL-C. Additionally, hepatic glutathione, Na/K-ATPase, and glutathione peroxidase, as well as serum HDL-C, total protein and albumin levels were significantly reduced. Moreover, BLM injection resulted in marked histopathological alterations and severe expression of caspase 3. Post-treatment of BLM-intoxicated rats with LF, SeNPs or LF/SeNPs combination obviously improved the BLM-induced hepatic damages; this was achieved from the marked modulations in the mentioned parameters, besides improving the histopathological hepatic architecture. It is worth mentioning that LF/SeNPs exerted the greatest potency. In conclusion, the obtained results demonstrated that LF, SeNPs and LF/SeNPs succeeded in attenuating the BLM-induced hepatic dysfunction. Therefore, these supplements might be used to protect against drug-associated side effects.

摘要

本研究旨在评估牛乳铁蛋白(LF)、硒纳米粒子(SeNPs)或其组合(LF/SeNPs)对博来霉素(BLM)诱导的肝损伤的肝脏和免疫改善潜力。将 50 只成年雄性大鼠(160-200g)等分为 5 组:(1)生理盐水对照组,(2)BLM 注射组(15mg/kg,每周两次,ip),和(3-5)组用 LF(200mg/kg/天)、SeNPs(0.0486mg/kg/天)或 LF/SeNPs 组合(200.0486mg/kg/天)口服治疗,在 BLM 中毒后 6 周。采集血液和肝脏样本进行生化、组织病理学和免疫组织化学分析。结果显示,BLM 导致肝脂质过氧化和一氧化氮显著增加,以及血清肝功能标志物(AST、ALT 和 GGT 活性)、GM-CSF、CD4、TNF-α、IL-1β、TGF-β1、纤维连接蛋白、甘油三酯、胆固醇和 LDL-C 水平升高。此外,肝谷胱甘肽、Na/K-ATP 酶和谷胱甘肽过氧化物酶以及血清 HDL-C、总蛋白和白蛋白水平显著降低。此外,BLM 注射导致明显的组织病理学改变和 caspase 3 的严重表达。BLM 中毒大鼠用 LF、SeNPs 或 LF/SeNPs 组合治疗后,明显改善了 BLM 诱导的肝损伤;这是通过对上述参数的明显调节来实现的,此外还改善了肝组织学结构。值得注意的是,LF/SeNPs 发挥了最大的功效。总之,研究结果表明 LF、SeNPs 和 LF/SeNPs 成功减轻了 BLM 诱导的肝功能障碍。因此,这些补充剂可能用于预防药物相关的副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f76e/11387485/446b4ce421f8/41598_2024_70894_Fig1_HTML.jpg

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