Silymarin Encapsulated Liposomal Formulation: An Effective Treatment Modality against Copper Toxicity Associated Liver Dysfunction and Neurobehavioral Abnormalities in Wistar Rats

水飞蓟素包覆脂质体制剂:一种治疗 Wistar 大鼠铜毒性相关肝功能障碍和神经行为异常的有效方法

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作者:Tuba Maryam, Nosheen Fatima Rana, Sultan M Alshahrani, Farhat Batool, Misha Fatima, Tahreem Tanweer, Salma Saleh Alrdahe, Yasmene F Alanazi, Ifat Alsharif, Fatima S Alaryani, Amer Sohail Kashif, Farid Menaa

Abstract

Wilson's disease causes copper accumulation in the liver and extrahepatic organs. The available therapies aim to lower copper levels by various means. However, a potent drug that can repair the damaged liver and brain tissue is needed. Silymarin has hepatoprotective, antioxidant, and cytoprotective properties. However, poor oral bioavailability reduces its efficacy. In this study, a "thin film hydration method" was used for synthesizing silymarin-encapsulated liposome nanoparticles (SLNPs) and evaluated them against copper toxicity, associated liver dysfunction and neurobehavioral abnormalities in Wistar rats. After copper toxicity induction, serological and behavioral assays were conducted to evaluate treatment approaches. Histological examination of the diseased rats revealed severe hepatocyte necrosis and neuronal vacuolation. These cellular degenerations were mild in rats treated with SLNPs and a combination of zinc and SLNPs (ZSLNPs). SLNPs also decreased liver enzymes and enhanced rats' spatial memory significantly (p = 0.006) in the diseased rats. During forced swim tests, SLNPs treated rats exhibited a 60-s reduction in the immobility period, indicating reduced depression. ZSLNPs were significantly more effective than traditional zinc therapy in decreasing the immobility period (p = 0.0008) and reducing liver enzymes, but not in improving spatial memory. Overall, SLNPs enhanced oral silymarin administration and managed copper toxicity symptoms.

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