Prospective Hepatoprotective Actions of Novel Nano-formulations of Sildenafil and Neem Extract in Counteracting Oral Carbon Tetrachloride-induced Liver Injury in Rats

IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Mahmoud S. Sabra, Essmat A. H. Allam, Madeha H. A. Darwish, Al-Hassan Mohammed Mostafa, Abeer S. Hassan, Marwa G. Gamea, Dalia Hassan, Mohamed M. Elbadr
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引用次数: 0

Abstract

Purpose

A multitude of inflammatory cells and chemical mediators initiate a complex cascade that ultimately leads to hepatocyte death and a systemic inflammatory response. This research aimed to investigate the potential effects of sildenafil and neem (Azadirachta indica) extract, in both conventional and nanoparticle (NP) forms, in the treatment of moderate acute liver damage induced by orogastric carbon tetrachloride (CCL4).

Methods

To induce moderate acute hepatic damage a single oral dosage of CCL4 (2.5 mL/kg body weight) was provided 24 h before euthanasia. In liver damage-induced CCL4, sildenafil and neem extract were given in conventional and nanoparticle (PLGA or niosome) forms. To find histological anomalies and hepatic changes, behavioral, biochemical, histopathological, and immunohistochemical methods were used.

Results

The findings indicated that sildenafil and/or neem extract, especially in NP combination, significantly mitigated CCL4-induced acute moderate liver damage. Indicators of liver function, including aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), albumin, bilirubin and gamma-glutamyl transferase (GGT), shown improvement, particularly with the nanoparticulation of both therapies. Treatment, particularly in NP forms, improved the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase activity (GPx) in liver tissues. A significant reduction in NF-κB expression in hepatic tissue was shown in treatment groups. Also, medication resulted in lower levels of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), caspase-3, and transforming growth factor-beta (TGF-β) in the liver tissue homogenates. Liver function was more significantly improved by the drug-NP combination.

Conclusions

This study verified the beneficial therapeutic effects of the combination of sildenafil and neem extract, particularly in NP forms, using biochemical, histological, and immunohistochemical analyses in a rat model of liver damage.

新型纳米西地那非和楝树提取物对口服四氯化碳诱导大鼠肝损伤的前瞻性保护作用
目的多种炎症细胞和化学介质启动复杂的级联反应,最终导致肝细胞死亡和全身炎症反应。本研究旨在探讨西地那非和印楝(印楝)提取物在常规和纳米颗粒(NP)形式下治疗胃四氯化碳(CCL4)诱导的中度急性肝损伤的潜在作用。方法安乐死前24 h单次口服CCL4 (2.5 mL/kg体重)诱导中度急性肝损伤。在肝损伤诱导的CCL4中,西地那非和楝树提取物以常规和纳米颗粒(PLGA或niosome)形式给予。采用行为学、生物化学、组织病理学和免疫组织化学方法观察组织学异常和肝脏变化。结果西地那非和/或楝树提取物,特别是NP联合用药,可显著减轻ccl4诱导的急性中度肝损伤。肝功能指标,包括天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)、丙氨酸转氨酶(ALT)、白蛋白、胆红素和γ -谷氨酰转移酶(GGT),都显示出改善,特别是两种治疗的纳米连接。处理,特别是NP形式的处理,改善了肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPx)的水平。治疗组大鼠肝组织中NF-κB表达明显降低。此外,药物治疗导致肝组织匀浆中白细胞介素-1β (IL-1β)、肿瘤坏死因子α (TNF-α)、caspase-3和转化生长因子β (TGF-β)水平降低。药物- np联合用药对肝功能的改善更为显著。本研究通过对大鼠肝损伤模型的生化、组织学和免疫组织化学分析,证实了西地那非和楝树提取物联合使用的有益治疗效果,特别是NP形式。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Pharmaceutical Innovation
Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-
CiteScore
3.70
自引率
3.80%
发文量
90
审稿时长
>12 weeks
期刊介绍: The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.
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