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负载姜黄素的壳聚糖纳米颗粒在减轻辐射诱导的肝损伤中的辐射防护作用及增强疗效

Radioprotection and enhanced efficacy by curcumin-loaded chitosan nanoparticles in mitigating radiation-induced liver injury.

作者信息

Azmoonfar Rasool, Moslehi Masoud, Shahbazi-Gahrouei Daryoush, Shiri Elham, Azizi Mehdi

机构信息

Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Medical Physics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

Biochem Biophys Res Commun. 2025 Mar 19;753:151512. doi: 10.1016/j.bbrc.2025.151512. Epub 2025 Feb 18.

Abstract

INTRODUCTION

This study aimed to evaluate the protective effect of curcumin-loaded chitosan nanoparticles (Cur-CsNPs) against radiation-induced liver damage in rats. Curcumin's antioxidant and anti-inflammatory properties, combined with chitosan's drug delivery potential, were leveraged to mitigate the harmful effects of ionizing radiation (IR) on the liver.

METHODS

Cur-CsNPs were characterized using TEM, XRD, DLS, and FTIR. Spectrophotometry assessed drug loading and curcumin release. Cytotoxicity was evaluated using MTT assay on HepG2 cells. The experimental design involved eight groups: a control group, three groups receiving different doses of Cur-CsNPs (25, 50, 100 mg/kg), three groups receiving the same doses plus irradiation (6Gy), and one group receiving irradiation only. H&E and MTC staining were used for histopathological evaluation. The activity of liver enzymes ALT, AST, ALP, and GGT was measured.

RESULTS

In this study, three types of Cur-CsNPs were synthesized using varying ratios of chitosan to TPP ratios, resulting in average sizes of 660 nm, 230 nm, and 120 nm. Cur-CsNPs which exhibited the highest encapsulation efficiency, was selected for further evaluation. TEM confirmed its spherical shape with an average size of 37 nm. Drug release studies demonstrated an 85 % release at pH 5.4 within 70 h. MTT assays indicated low cytotoxicity, with high cell viability maintained across all concentrations and time points. Liver enzyme analysis in rats revealed that Cur-CsNPs, particularly when combined with radiation, mitigated radiation-induced liver damage. Histological examination showed that treatment with Cur-CsNPs reduced liver damage, inflammation, necrosis, and fibrosis in irradiated groups compared to the radiation-only group, which exhibited severe liver damage.

CONCLUSION

The findings of this study show that Cur-CsNPs possess significant potential as a therapeutic agent for protecting against radiation-induced liver injury. The favorable drug release profile, low cytotoxicity, and protective effects observed in enzyme levels and histological assessments highlight the efficacy of Cur-CsNPs. The findings imply that Cur-CsNPs could be an effective strategy for enhancing liver protection in radiation exposure scenarios, warranting further investigation into their mechanisms of action and potential clinical applications.

摘要

引言

本研究旨在评估载姜黄素壳聚糖纳米粒(Cur-CsNPs)对大鼠辐射诱导肝损伤的保护作用。姜黄素的抗氧化和抗炎特性,结合壳聚糖的药物递送潜力,被用于减轻电离辐射(IR)对肝脏的有害影响。

方法

使用透射电子显微镜(TEM)、X射线衍射(XRD)、动态光散射(DLS)和傅里叶变换红外光谱(FTIR)对Cur-CsNPs进行表征。采用分光光度法评估载药量和姜黄素释放情况。使用MTT法在HepG2细胞上评估细胞毒性。实验设计包括八组:一组对照组,三组接受不同剂量Cur-CsNPs(25、50、100mg/kg)的组,三组接受相同剂量并加照射(6Gy)的组,以及一组仅接受照射的组。采用苏木精-伊红(H&E)和马松三色(MTC)染色进行组织病理学评估。测量肝酶谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)和γ-谷氨酰转移酶(GGT)的活性。

结果

在本研究中,使用不同壳聚糖与三聚磷酸钠(TPP)比例合成了三种类型的Cur-CsNPs,平均粒径分别为660nm、230nm和120nm。选择包封率最高的Cur-CsNPs进行进一步评估。TEM证实其呈球形,平均粒径为37nm。药物释放研究表明,在pH 5.4条件下70小时内释放率为85%。MTT分析表明细胞毒性低,在所有浓度和时间点均保持高细胞活力。大鼠肝酶分析显示,Cur-CsNPs,特别是与辐射联合使用时,可减轻辐射诱导的肝损伤。组织学检查表明,与仅接受辐射且表现出严重肝损伤的组相比,Cur-CsNPs治疗可减轻照射组的肝损伤、炎症、坏死和纤维化。

结论

本研究结果表明,Cur-CsNPs作为预防辐射诱导肝损伤的治疗剂具有巨大潜力。在酶水平和组织学评估中观察到的良好药物释放曲线、低细胞毒性和保护作用突出了Cur-CsNPs的疗效。研究结果表明,Cur-CsNPs可能是在辐射暴露情况下增强肝脏保护的有效策略,值得进一步研究其作用机制和潜在临床应用。

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