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芝麻酚负载固体脂质纳米粒对四氯化碳诱导的大鼠亚慢性肝毒性的肝保护作用

Hepatoprotective effects of sesamol loaded solid lipid nanoparticles in carbon tetrachloride induced sub-chronic hepatotoxicity in rats.

作者信息

Singh Neha, Khullar Neeraj, Kakkar Vandita, Kaur Indu Pal

机构信息

Department of Biotechnology, Panjab University, Chandigarh, 160014, India.

Department of Pharmaceutics, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India.

出版信息

Environ Toxicol. 2016 May;31(5):520-32. doi: 10.1002/tox.22064. Epub 2014 Nov 20.

Abstract

Sesamol is a phenolic component of sesame seed oil, which has been established as an antioxidant and also possesses potential for hepatoprotection. However, its protective role in carbon tetrachloride (CCl4 ) induced sub-chronic hepatotoxicity has not been studied. Limited oral bioavailability (BA) and rapid elimination (as conjugates) in rats is reported for sesamol. Considering its significant antioxidant potential and compromised BA, we packaged sesamol into solid lipid nanoparticles (S-SLNs) to enhance its hepatoprotective bioactivity. S-SLNs prepared by microemulsification method were nearly spherical in shape with an average particle size of 120.30 nm and their oral administration at 8 mg/kg body weight (BW) showed significantly (p < 0.001) better hepatoprotection than free sesamol (FS) and a well established hepatoprotective antioxidant silymarin [SILY (25 mg/kg BW); p < 0.05) in CCl4 induced sub-chronic liver injury in rats. Evaluations were done in terms of histological changes in the liver tissue, liver injury markers (serum alanine aminotransferase, serum aspartate aminotransferase, and serum lactate dehydrogenase); oxidative stress markers (lipid peroxidation, superoxide dismutase, and reduced glutathione) and proinflammatory response marker (tumor necrosis factor-alpha).

摘要

芝麻酚是芝麻油中的一种酚类成分,已被确认为一种抗氧化剂,并且具有肝脏保护潜力。然而,其在四氯化碳(CCl4)诱导的亚慢性肝毒性中的保护作用尚未得到研究。据报道,芝麻酚在大鼠体内口服生物利用度(BA)有限且消除迅速(以共轭物形式)。考虑到其显著的抗氧化潜力和较低的BA,我们将芝麻酚包装成固体脂质纳米粒(S-SLNs)以增强其肝脏保护生物活性。通过微乳化法制备的S-SLNs形状近似球形,平均粒径为120.30 nm,以8 mg/kg体重(BW)口服给药时,在CCl4诱导的大鼠亚慢性肝损伤中,其肝脏保护作用显著优于游离芝麻酚(FS)和一种成熟的具有肝脏保护作用的抗氧化剂水飞蓟素[SILY(25 mg/kg BW);p<0.05]。评估是根据肝组织的组织学变化、肝损伤标志物(血清丙氨酸氨基转移酶、血清天冬氨酸氨基转移酶和血清乳酸脱氢酶)、氧化应激标志物(脂质过氧化、超氧化物歧化酶和还原型谷胱甘肽)以及促炎反应标志物(肿瘤坏死因子-α)进行的。

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