Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Department of Pathology, Imam Reza Hospital, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Biochem Biophys Res Commun. 2023 Oct 8;676:103-108. doi: 10.1016/j.bbrc.2023.07.045. Epub 2023 Jul 21.
Acetaminophen (Act) overdose is a known inducer of liver failure in both children and adults. Cell annihilation ensues following acetaminophen overdose and its toxic metabolites by depleting cellular GSH storage and increasing ROS levels. Silymarin extract and its major compound silibinin (SLB) possess robust antioxidant properties by inducing ROS elimination; however, low bioavailability and rapid metabolism limit their applications. Herein, we aimed at using SLB liposomes to combat acetaminophen-induced acute liver toxicity.
We have developed a SLB-lipid complex to improve SLB loading efficiency within nanoliposome by using the lipid film method. Liposomes were characterized by using DLS and TEM analysis, and the release pattern, and toxicity profile on the normal cells as well as histopathological and serum analysis were investigated to reveal relevant enzyme activities in an animal model.
Data demonstrated that negatively-charged SLB liposomes of 115 nm had homogeneous spherical morphology, and entrapped a considerable quantity of SLB of almost 40%. Liposomes shows a favorable release pattern and were not toxic against NIH3T3 mouse fibroblast cells. The animal study revealed that treatment of mice with SLB nanoliposomes could significantly preserve liver function as revealed by the reduced levels of ALT and AST hepatic enzymes as well as ALP in the serum. Our data indicated that intraperitoneal administration of SLB Lip could significantly reduce ALT enzyme levels (p < 0.05) compared to N-acetylcysteine, while i.v administration resulted in no significant difference compared to control animals with no treatment.
The results of this study support the significant hepatoprotective effect of SLB nanoliposomes against acetaminophen-induced toxicity depending on the route of administration.
对乙酰氨基酚（Act）过量是儿童和成人肝衰竭的已知诱因。对乙酰氨基酚过量及其有毒代谢物通过耗尽细胞 GSH 储存并增加 ROS 水平，导致细胞坏死。水飞蓟素提取物及其主要化合物水飞蓟宾（SLB）通过诱导 ROS 消除具有强大的抗氧化特性；然而，低生物利用度和快速代谢限制了它们的应用。在此，我们旨在使用 SLB 脂质体来对抗对乙酰氨基酚引起的急性肝毒性。
我们已经开发了一种 SLB-脂质复合物，通过使用脂质膜法提高纳米脂质体中 SLB 的负载效率。通过 DLS 和 TEM 分析对脂质体进行了表征，并研究了其在正常细胞中的释放模式和毒性概况以及组织病理学和血清分析，以揭示动物模型中相关酶活性。
数据表明，带负电荷的 115nm SLB 脂质体具有均匀的球形形态，并且包封了几乎 40%的相当数量的 SLB。脂质体表现出良好的释放模式，对 NIH3T3 小鼠成纤维细胞没有毒性。动物研究表明，用 SLB 纳米脂质体治疗小鼠可以显著保护肝功能，表现为血清中 ALT 和 AST 肝酶以及 ALP 的水平降低。我们的数据表明，与 N-乙酰半胱氨酸相比，腹腔内给予 SLB Lip 可以显著降低 ALT 酶水平（p<0.05），而静脉内给予 SLB Lip 与未治疗的对照动物相比没有显著差异。
根据给药途径，本研究结果支持 SLB 纳米脂质体对乙酰氨基酚诱导的毒性具有显著的肝保护作用。
