Assessment of Toxicity of Myristicin and 1’-Hydroxymyristicin in HepG2 Cell Line

L. Marabini, Laura Neglia, E. Monguzzi, C. Galli, M. Marinovich
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引用次数: 6

Abstract

Background and Objective: Myristicin belongs to a class of potentially toxic chemicals (alkoxy substituted allylbenzenes) and despite the structural analogy with safrole, data on this compound are very controversial and unclear. In this study assessed the cytotoxic and genotoxic potential of myristicin and 1’-hydroxy-myristicin after 24 h of exposure in HepG2 cells. Methodology: The compounds were tested up to 600 μM concentration, for 24 h. The genotoxicity was assessed with alkaline and neutral comet assay and micronucleus assay. The data were analysed by one-way ANOVA. Results: It is to be emphasized that only the synthetic Phase 1 metabolite (1’-hydroxymyristicin) showed a genotoxic effect starting from the concentration of 150 μM both in comet and micronucleus tests. However, it is important to point out that the same concentration cause a statistically significant (p<0.001) apoptotic process. Conclusion: The consumption of a traditional diet determines very low levels of exposure to the parent myristicin. This fact implies as the primary metabolic pathway the O-demethylation (5-allyl-2,3-dihidroxyanisole) and not to Phase I metabolism, which leads to the conclusion that this substance could not present a significant risk to humans.
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肉豆蔻素和1′-羟基肉豆蔻素对HepG2细胞株的毒性评价
背景与目的:肉豆蔻素属于一类具有潜在毒性的化学物质(烷氧基取代烯基苯),尽管其结构与黄樟酚相似,但有关该化合物的数据非常有争议和不清楚。本研究评估了肉豆蔻素和1′-羟基肉豆蔻素在HepG2细胞暴露24小时后的细胞毒性和基因毒性潜力。方法:在600 μM浓度下检测化合物24 h,采用碱性、中性彗星试验和微核试验评估遗传毒性。数据采用单因素方差分析。结果:在彗星和微核试验中,只有人工合成的1期代谢物(1′-羟基肉豆蔻素)在浓度为150 μM时才表现出基因毒性作用。然而,重要的是要指出,相同的浓度导致统计学上显著(p<0.001)的凋亡过程。结论:传统饮食的消耗决定了母体肉豆蔻素的暴露水平非常低。这一事实表明,o -去甲基化(5-烯丙基-2,3-二氢氧异构体)是主要的代谢途径,而不是I期代谢,从而得出结论,该物质不会对人类产生重大风险。
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