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Environ Toxicol ; 33(2): 167-177, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29143438

ABSTRACT

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.


Subject(s)
Chemical and Drug Induced Liver Injury/prevention & control , Lysosomes/drug effects , Mitochondria/drug effects , Nanoparticles/chemistry , Protective Agents/pharmacology , Ubiquinone/analogs & derivatives , Animals , Antioxidants/metabolism , Cell Survival/drug effects , Cells, Cultured , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/metabolism , Dichlorvos/toxicity , Glutathione/metabolism , Hepatocytes/cytology , Hepatocytes/drug effects , Hepatocytes/metabolism , Lipid Peroxidation/drug effects , Lysosomes/metabolism , Male , Membrane Potential, Mitochondrial/drug effects , Mitochondria/metabolism , Protective Agents/chemistry , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , Ubiquinone/chemistry , Ubiquinone/pharmacology
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