Hayyan Maan, Looi Chung Yeng, Hayyan Adeeb, Wong Won Fen, Hashim Mohd Ali
Department of Civil Engineering, University of Malaya, Kuala Lumpur, Malaysia; University of Malaya Centre for Ionic Liquids (UMCiL), University of Malaya, Kuala Lumpur, Malaysia.
Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
PLoS One. 2015 Feb 13;10(2):e0117934. doi: 10.1371/journal.pone.0117934. eCollection 2015.
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.
研究了具有四种氢键供体（即甘油（Gl）、乙二醇（EG）、三甘醇（TEG）和尿素（U））的铵基深层共熔溶剂（DESs）的细胞毒性潜力。使用体外细胞系和体内动物模型检测了DESs的毒性。为了进行比较，测定了DESs、其单个组分及其组合作为水溶液的半数抑制浓度（IC50）和选择性指数。DESs的细胞毒性作用因细胞系而异。对于OKF6、MCF-7、A375、HT29和H413细胞，GlDES、EGDES、UDES和TEGDES的IC50分别遵循TEGDES<GlDES<EGDES<UDES的顺序。GlDES对MCF-7和A375具有选择性，EGDES对MCF-7、PC3、HepG2和HT29具有选择性，UDES对MCF-7、PC3、HepG2和HT29具有选择性，TEGDES对MCF-7和A375具有选择性。然而，使用ICR小鼠进行的急性毒性研究表明，与它们的单个组分相比，这些DESs具有相对较高的毒性。DES不会导致DNA损伤，但它可以增强活性氧的产生并诱导处理过的癌细胞凋亡，显著的乳酸脱氢酶释放证明了这一点。此外，与离子液体相比，所检测的DESs显示出较低的细胞毒性。据我们所知，这是首次展示DESs的体外和体内联合毒性概况，这引发了这些新型混合物的毒性问题及其用于治疗目的的潜在适用性。
