Protective effects of coenzyme Q10 nanoparticles on dichlorvos‐induced hepatotoxicity and mitochondrial/lysosomal injury

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.

Coenzyme Q10 supplementation mitigates piroxicam-induced oxidative injury and apoptotic pathways in the stomach, liver, and kidney

“…In that study, CoQ10 reduced the cisplatin-induced LPO and restored the decreased level of GSH and activities of CAT and SOD in renal tissue. Also showing the beneficial antioxidant power of CoQ10, another related study was conducted by Eftekhari et al [ 64 ]. This study demonstrated the potential role of CoQ10 in attenuating dichlorvos-induced oxidative damage and mitochondrial dysfunction in hepatic tissue.…”

Neurotoxicity in acute and repeated organophosphate exposure

“…Eftekhari and colleagues demonstrated that nanoparticle based delivery of CoQ10 is effective in protecting against dichlorvos induced hepatotoxicity. Here, the authors demonstrated protection against mitochondrial dysfunction and the generation of reactive oxygen species with increased bioavailability over traditional CoQ10 (Eftekhari et al, 2018).…”

Reactive Oxygen Species‐Regulating Strategies Based on Nanomaterials for Disease Treatment

“…For example, GSH has been successfully installed in self‐assembled NPs based on poly(ethylene glycol) diacrylate (PEGDA) to protect human brain neuroblastoma cells (SH‐SY5Y) from oxidative stress. [ 56 ] Among non‐enzymatic antioxidants, some exogenous supplements of antioxidants involving natural and synthetic antioxidants can also be used to strengthen antioxidant defence system, mainly including some small‐molecule ROS scavengers such as vitamin family (e.g., retinoids (vitamin A), ascorbic acid (vitamin C), tocopherol (vitamin E)), [ 59 ] Coenzyme Q10 (CoQ10), [ 60 ] N ‐Acetylcysteine, [ 61 ] polyphenol antioxidants, [ 62 ] carotenoids (e.g., lycopene and β ‐carotene), [ 63 ] Edaravone (Radicut), [ 64 ] and NXY‐059 (Cerovive). [ 65 ] Up to now, the delivery strategies of above non‐enzymatic antioxidants have been widely studied by employing a variety of delivery vehicles such as liposomes, solid lipid NPs, micelles, mesoporous silica, bamboo charcoal NPs, and silica‐coated Au NPs.…”