Doxorubicin Loaded Gold Nanoparticles Mitigate Liver Fibrosis and Inflammatory Cytokines Gene Expression in Rat.

Yasmeen Ishaq, Hamna Naeem, Sana Khurshid, Rabia Tabbasam, Zeeshan Haider
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Abstract

Background: Gold nanoparticles have the potential to be used as a carrier in drug delivery systems due to their small size, large surface area and short circulation time in blood.

Objective: This study demonstrates that doxorubicin conjugation with gold nanoparticles (AuNPs) may reduce its toxicity as well as improve therapeutic efficacy.

Methods: Five groups of Albino rats were used; 1: healthy control, 2: injured, 3: injured and treated with Dox, 4: injured and treated with AuNPs, 5: injured and treated with AuNPs: Dox. At the end of the experiment, blood and liver tissues were processed for biochemical and histopathological analysis. The expression of collagen, HO-1, IL-6 and TNF-α genes involved in liver fibrosis was observed through real-time PCR.

Results: At the end of the experiment, it was observed that the body weights of DOX-treated rats decreased by 0.72%, however, AuNPs and Au: DOX-treated rats were 15.3% and 29.13% respectively. The percentage of liver protection determined through alanine aminotransferase and aspartate aminotransferase levels in DOX, AuNPs and AuNPs: DOX treated groups were 39.21%, 79.26%, 98.17% and 47.77%, 84.17%, 97.92%, respectively, representing better recovering liver in Dox-AuNPs treated rats compared to others. Histopathological and gene expression studies further support the findings. The mRNA expression levels of inflammatory and oxidative stress-related genes HO-1, IL-6 and TNF- α were upregulated in the injured group but downregulated in the treated group.

Conclusion: As depicted through biochemical, histopathological and gene expression studies, Au: DOX conjugate group seems to be protective against liver fibrosis.

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负载多柔比星的金纳米粒子可减轻大鼠肝纤维化和炎症细胞因子基因表达
背景:由于金纳米粒子体积小、表面积大、在血液中的循环时间短,因此有望用作药物输送系统的载体:金纳米颗粒具有体积小、表面积大、血液循环时间短等特点,因此有可能被用作给药系统的载体:本研究旨在探讨多柔比星与金纳米颗粒(AuNPs)共轭可降低其毒性并提高疗效:使用五组白化大鼠:1:健康对照组;2:受伤组;3:受伤并用 Dox 治疗组;4:受伤并用 AuNPs 治疗组;5:受伤并用 AuNPs 治疗组:Dox。实验结束后,对血液和肝组织进行生化和组织病理学分析。通过实时 PCR 检测肝纤维化相关基因胶原、HO-1、IL-6 和 TNF-α 的表达:结果:实验结束时,DOX 治疗大鼠的体重下降了 0.72%,而 AuNPs 和 Au:DOX治疗大鼠的体重分别下降了15.3%和29.13%。通过丙氨酸氨基转移酶和天门冬氨酸氨基转移酶水平测定,DOX、AuNPs 和 AuNPs:DOX 处理组的肝脏保护率分别为 39.21%、39.21%和 39.21%:DOX、AuNPs 和 AuNPs:DOX 治疗组的丙氨酸氨基转移酶和天门冬氨酸氨基转移酶水平分别为 39.21%、79.26%、98.17% 和 47.77%、84.17%、97.92%。这表明与其他组相比,Dox-AuNPs 处理组大鼠的肝脏恢复情况更好。组织病理学和基因表达研究进一步支持了上述发现。炎症和氧化应激相关基因 HO-1、IL-6 和 TNF-α 的 mRNA 表达水平在损伤组上调,而在治疗组下调:结论:通过生化、组织病理学和基因表达研究,Au:结论:通过生化、组织病理学和基因表达研究,Au:DOX 共轭物组似乎对肝纤维化具有保护作用。
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