Di Nunzio Mattia, Valli Veronica, Tomás-Cobos Lidia, Tomás-Chisbert Teresa, Murgui-Bosch Lucía, Danesi Francesca, Bordoni Alessandra
Interdepartmental Centre for Industrial Agri-Food Research, University of Bologna, Piazza Goidanich 60, 47521, Cesena, Italy.
Department of Agri-Food Sciences and Technologies, University of Bologna, Piazza Goidanich 60, 47521, Cesena, Italy.
BMC Complement Altern Med. 2017 Sep 7;17(1):453. doi: 10.1186/s12906-017-1962-2.
Foodstuffs of both plant and animal origin contain a wide range of bioactive compounds. Although human intervention studies are mandatory to assess the health effects of bioactives, the in vitro approach is often used to select the most promising molecules to be studied in vivo. To avoid misleading results, concentration and chemical form, exposure time, and potential cytotoxicity of the tested bioactives should be carefully set prior to any other experiments.
In this study the possible cytotoxicity of different bioactives (docosahexaenoic acid, propionate, cyanidin-3-O-glucoside, protocatechuic acid), was investigated in HepG2 cells using different methods. Bioactives were supplemented to cells at different concentrations within the physiological range in human blood, alone or in combination, considering two different exposure times.
Reported data clearly evidence that in vitro cytotoxicity is tightly related to the exposure time, and it varies among bioactives, which could exert a cytotoxic effect even at a concentration within the in vivo physiological blood concentration range. Furthermore, co-supplementation of different bioactives can increase the cytotoxic effect.
Our results underline the importance of in vitro cytotoxicity screening that should be considered mandatory before performing studies aimed to evaluate the effect of bioactives on other cellular parameters. Although this study is far from the demonstration of a toxic effect of the tested bioactives when administered to humans, it represents a starting point for future research aimed at verifying the existence of a potential hazard due to the wide use of high doses of multiple bioactives.
动植物来源的食品都含有多种生物活性化合物。虽然评估生物活性物质的健康影响必须进行人体干预研究，但体外方法通常用于筛选最有前景的分子以便进行体内研究。为避免产生误导性结果，在进行任何其他实验之前，应仔细设定受试生物活性物质的浓度、化学形式、暴露时间和潜在细胞毒性。
在本研究中，使用不同方法在HepG2细胞中研究了不同生物活性物质（二十二碳六烯酸、丙酸、花青素-3-O-葡萄糖苷、原儿茶酸）的潜在细胞毒性。在人体血液生理范围内，将生物活性物质以不同浓度单独或组合添加到细胞中，并考虑两种不同的暴露时间。
报告的数据清楚地表明，体外细胞毒性与暴露时间密切相关，并且在生物活性物质之间存在差异，即使在体内生理血液浓度范围内的浓度下也可能发挥细胞毒性作用。此外，不同生物活性物质的联合添加可增强细胞毒性作用。
我们的结果强调了体外细胞毒性筛选的重要性，在进行旨在评估生物活性物质对其他细胞参数影响的研究之前，应将其视为必需步骤。尽管本研究远未证明受试生物活性物质对人类给药时的毒性作用，但它代表了未来研究的一个起点，旨在验证由于广泛使用高剂量多种生物活性物质而存在潜在危害的情况。
