title: In Vitro and In Vivo toxicity profiling of ammonium-based deep eutectic solvents.
abstract: The cytotoxic potential of ammonium-based deep eutectic solvents (DESs) with four hydrogen bond donors, namely glycerine (Gl), ethylene glycol (EG), triethylene glycol (TEG) and urea (U) were investigated. The toxicity of DESs was examined using In Vitro cell lines and In Vivo animal model. IC50 and selectivity index were determined for the DESs, their individual components and their combinations as aqueous solutions for comparison purposes. The cytotoxicity effect of DESs varied depending on cell lines. The IC50 for the GlDES, EGDES, UDES and TEGDES followed the sequence of TEGDES< GlDES< EGDES< UDES for OKF6, MCF-7, A375, HT29 and H413, respectively. GlDES was selective against MCF-7 and A375, EGDES was selective against MCF-7, PC3, HepG2 and HT29, UDES was selective against MCF-7, PC3, HepG2 and HT29, and TEGDES was selective against MCF-7 and A375. However, acute toxicity studies using ICR mice showed that these DESs were relatively toxic in comparison to their individual components. DES did not cause DNA damage, but it could enhance ROS production and induce apoptosis in treated cancer cells as evidenced by marked LDH release. Furthermore, the examined DESs showed less cytotoxicity compared with ionic liquids. To the best of our knowledge, this is the first time that combined In Vitro and In Vivo toxicity profiles of DESs were being demonstrated, raising the toxicity issue of these neoteric mixtures and their potential applicability to be used for therapeutic purposes.
authors: Department of Civil Engineering, University of Malaya, Kuala Lumpur, Malaysia; University of Malaya Centre for Ionic Liquids (UMCiL), University of Malaya, Kuala Lumpur, Malaysia.
authors: Maan
authors: M
authors: Hayyan
authors: Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: Chung Yeng
authors: CY
authors: Looi
authors: University of Malaya Centre for Ionic Liquids (UMCiL), University of Malaya, Kuala Lumpur, Malaysia; Department of Chemical Engineering, University of Malaya, Kuala Lumpur, Malaysia.
authors: Adeeb
authors: A
authors: Hayyan
authors: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors: Won Fen
authors: WF
authors: Wong
authors: University of Malaya Centre for Ionic Liquids (UMCiL), University of Malaya, Kuala Lumpur, Malaysia; Department of Chemical Engineering, University of Malaya, Kuala Lumpur, Malaysia.
authors: Mohd Ali
authors: MA
authors: Hashim
mesh_terms: D064751:Ammonium Compounds / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D045022:Lactate Dehydrogenases / Q000096:biosynthesis; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism; D012997:Solvents / Q000737:chemistry* / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D064751:Ammonium Compounds; D000975:Antioxidants; D017382:Reactive Oxygen Species; D012997:Solvents; D045022:Lactate Dehydrogenases