Eftekhari Aziz, Ahmadian Elham, Azami Aida, Johari-Ahar Mohammad, Eghbal Mohammad Ali
Department of Basic Sciences, Maragheh university of Medical Sciences, Maragheh, Iran.
Department of Pharmacology and Toxicology, Maragheh University of Medical Sciences, Maragheh, Iran.
Environ Toxicol. 2018 Feb;33(2):167-177. doi: 10.1002/tox.22505. Epub 2017 Nov 16.
Development of biocompatible antioxidant nanoparticles for xenobiotic-induced liver disease treatment by oral or parenteral administration is of great interest in medicine. In the current study, we demonstrate the protective effects of coenzyme Q10 nanoparticles (CoQ10-NPs) on hepatotoxicity induced by dichlorvos (DDVP) as an organophosphate. Although CoQ10 is an efficient antioxidant, its poor bioavailability has limited the applications of this useful agent. First, CoQ10-NPs were prepared then characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM). In DDVP-treated and non-treated hepatocytes in the presence of CoQ10-NPs, cell viability, the level of reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential (MMP), lysosome membrane integrity, and cellular glutathione (GSH) content were measured. The prepared CoQ10-NPs were mono-dispersed and had narrow size distribution with average diameter of 54 nm. In the in vivo study, we evaluated the enzymes, which are involved in the antioxidant system for maintenance of normal liver function. In comparison to nonparticulate CoQ10, the CoQ10-NPs efficiently decreased the ROS formation, lipid peroxidation and cell death. Also, particulate form of CoQ10 improved MMP, GSH level and lysosome membrane integrity. In the in vivo, study, we revealed that CoQ10-NPs were better hepatoprotective than its nonparticulate form (P < .05). Altogether, we propose that the CoQ10-NPs have potential capability to be used as a therapeutic and prophylactic agent for poisoning that is induced by organophosphate agents, especially in the case of DDVP. Furthermore, these positive remarks make this nanoparticle amenable for the treatment of xenobiotic-induced liver diseases.
通过口服或肠胃外给药开发用于治疗外源性物质诱导的肝病的生物相容性抗氧化纳米颗粒在医学领域引起了极大关注。在本研究中,我们证明了辅酶Q10纳米颗粒(CoQ10-NPs)对由敌敌畏(DDVP)这种有机磷酸酯诱导的肝毒性具有保护作用。尽管辅酶Q10是一种有效的抗氧化剂,但其较差的生物利用度限制了这种有用药物的应用。首先,制备了CoQ10-NPs,然后使用动态光散射(DLS)和透射电子显微镜(TEM)对其进行表征。在存在CoQ10-NPs的情况下,对经DDVP处理和未处理的肝细胞的细胞活力、活性氧(ROS)水平、脂质过氧化(LPO)、线粒体膜电位(MMP)、溶酶体膜完整性和细胞内谷胱甘肽(GSH)含量进行了测量。所制备的CoQ10-NPs呈单分散状态,粒径分布窄,平均直径为54nm。在体内研究中,我们评估了参与维持正常肝功能的抗氧化系统的酶。与非颗粒形式的辅酶Q10相比,CoQ10-NPs能有效减少ROS的形成、脂质过氧化和细胞死亡。此外,颗粒形式的辅酶Q10改善了MMP、GSH水平和溶酶体膜完整性。在体内研究中,我们发现CoQ10-NPs的肝保护作用优于其非颗粒形式(P<0.05)。总之,我们认为CoQ10-NPs有潜力用作有机磷酸酯类药物中毒的治疗和预防剂,尤其是在敌敌畏中毒的情况下。此外,这些积极的结果使这种纳米颗粒适用于治疗外源性物质诱导的肝病。