Department of Food Technology, Universitat Politècnica de València, Camino de Vera s/n, 46022, Valencia, Spain.
Department of Food Technology, Universitat Politècnica de València, Camino de Vera s/n, 46022, Valencia, Spain.
Food Chem Toxicol. 2022 Feb;160:112778. doi: 10.1016/j.fct.2021.112778. Epub 2021 Dec 24.
The cytotoxicity of carvacrol- and thymol-functionalised mesoporous silica microparticles (MCM-41) was assessed in the human hepatocarcinoma cell line (HepG2). Cell viability, lactate dehydrogenase (LDH) activity, reactive oxygen species (ROS) production, mitochondrial membrane potential (ΔΨm), lipid peroxidation (LPO) and apoptosis/necrosis analyses were used as endpoints. The results showed that both materials induced cytotoxicity in a time- and concentration-dependent manner, and were more cytotoxic than free essential oil components and bare MCM-41. This effect was caused by cell-particle interactions and not by degradation products released to the culture media, as demonstrated in the extract dilution assays. LDH release was a less sensitive endpoint than the MTT (thiazolyl blue tetrazolium bromide) assay, which suggests the impairment of the mitochondrial function as the primary cytotoxic mechanism. In vitro tests on specialised cell functions showed that exposure to sublethal concentrations of these materials did not induce ROS formation during 2 h of exposure, but produced LPO and ΔΨm alterations in a concentration-dependent manner when cells were exposed for 24 h. The obtained results generally support the hypothesis that the carvacrol- and thymol-functionalised MCM-41 microparticles induced toxicity in HepG2 cells by an oxidative stress-related mechanism that resulted in apoptosis through the mitochondrial pathway.
香芹酚和百里香酚功能化介孔硅微球（MCM-41）的细胞毒性在人肝癌细胞系（HepG2）中进行了评估。细胞活力、乳酸脱氢酶（LDH）活性、活性氧（ROS）产生、线粒体膜电位（ΔΨm）、脂质过氧化（LPO）和细胞凋亡/坏死分析被用作终点。结果表明，这两种材料均以时间和浓度依赖的方式诱导细胞毒性，并且比游离精油成分和裸 MCM-41 更具细胞毒性。这种作用是由细胞-颗粒相互作用引起的，而不是由释放到培养基中的降解产物引起的，这在提取物稀释试验中得到了证明。与 MTT（噻唑蓝溴化四唑）测定相比，LDH 释放是一个不太敏感的终点，这表明线粒体功能障碍是主要的细胞毒性机制。对特殊细胞功能的体外测试表明，在 2 小时的暴露时间内，这些材料的亚致死浓度不会诱导 ROS 形成，但当细胞暴露 24 小时时，会以浓度依赖的方式产生 LPO 和 ΔΨm 改变。获得的结果普遍支持以下假设：香芹酚和百里香酚功能化 MCM-41 微球通过与氧化应激相关的机制在 HepG2 细胞中诱导毒性，导致通过线粒体途径的细胞凋亡。
