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烟酰胺和抗坏血酸纳米粒对高脂高果糖饮食诱导的大鼠肝损伤的作用:一项对比研究。

Nicotinamide and ascorbic acid nanoparticles against the hepatic insult induced in rats by high fat high fructose diet: A comparative study.

机构信息

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Egypt.

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Egypt.

出版信息

Life Sci. 2020 Dec 15;263:118540. doi: 10.1016/j.lfs.2020.118540. Epub 2020 Oct 6.

Abstract

AIMS

Non-alcoholic fatty liver disease (NAFLD) caused by consumption of high levels of fat and sugars (HFHS) in diet is considered one of the most dangerous medical complications among children and adolescents. Nicotinamide is among the promising candidates in ameliorating HFHS diet-induced NAFLD, but its use is limited by the possibility of prompting hepatotoxicity in high doses. Ascorbic acid is another promising candidate, however its use as a hepatoprotective agent is limited by its chemical instability. Therefore, the aim of the study was to overcome their delivery limitations and enhance their hepatoprotective activity by loading into nanoparticles.

KEY FINDINGS

In the present study, upon incorporating nicotinamide or ascorbic acid in chitosan nanoparticles, they ameliorated the insulin-resistant status induced in rats by a high-fat-high-fructose (HFHF) diet. Both formulae decreased serum level of ALT and AST, as well as liver tissue total cholesterol, triglycerides and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels. They also decreased oxidative and nitrosative stresses along with a significant increase in the hepatocellular energy. The biochemical findings were further confirmed by histopathological examination. Finally from the obtained data it could be concluded that chitosan nicotinamide nanoparticles at a dose level (10 mg/kg, p.o.) demonstrated beneficial pharmacological effect with safer toxicity profile than chitosan ascorbic acid nanoparticles.

SIGNIFICANCE

Nicotinamide chitosan nanoparticles could be recommended as daily supplement in the recovery from NAFLD.

摘要

目的

由高脂肪和高糖饮食(HFHS)引起的非酒精性脂肪性肝病(NAFLD)被认为是儿童和青少年中最危险的医学并发症之一。烟酰胺是改善 HFHS 饮食诱导的 NAFLD 的有希望的候选药物之一,但由于高剂量可能会引起肝毒性,其使用受到限制。抗坏血酸也是一种有前途的候选药物,但其作为肝保护剂的使用受到其化学不稳定性的限制。因此,本研究的目的是通过负载到纳米颗粒中来克服它们的递药限制并增强其肝保护活性。

主要发现

在本研究中,将烟酰胺或抗坏血酸掺入壳聚糖纳米颗粒中,可改善高脂肪高果糖(HFHF)饮食诱导的大鼠胰岛素抵抗状态。两种配方均降低了血清 ALT 和 AST 水平,以及肝组织总胆固醇、甘油三酯和 8-羟基-2-脱氧鸟苷(8-OHdG)水平。它们还降低了氧化和硝化应激,同时显著增加了肝细胞能量。生化发现通过组织病理学检查得到进一步证实。最后,根据获得的数据可以得出结论,壳聚糖烟酰胺纳米颗粒在 10mg/kg(po)的剂量水平下表现出有益的药理作用,且毒性谱比壳聚糖抗坏血酸纳米颗粒更安全。

意义

烟酰胺壳聚糖纳米颗粒可作为 NAFLD 恢复的日常补充剂。

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