Is cytotoxicity a determinant of the different in vitro and in vivo effects of bioactives?

Abstract

BackgroundFoodstuffs 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.MethodsIn 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.ResultsReported 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.ConclusionsOur 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.

Dairy Propionibacterium freudenreichii ameliorates acute colitis by stimulating MUC2 expression in intestinal goblet cell in a DSS-induced colitis rat model

“…However, it is likely that the health-promoting effects of propionate are less studied than those of butyrate. On the other hand, propionate shows hepatotoxicity at the concentration over 70 μM 39 . Therefore, the administration of a high concentration of propionate might not be an effective method to obtain beneficial effects.…”

Health benefits of ancient grains. Comparison among bread made with ancient, heritage and modern grain flours in human cultured cells

“…Once a week, cells were split 1:20 into a new 75 cm 2 flask, and the medium was refreshed (Di Nunzio et al, 2017). Cells were seeded in 12-well plates at the concentration of 8 × 10 5 cells/mL.…”

“…24 h supplementation. To avoid misleading results, cytotoxicity screening should be considered mandatory before performing in vitro studies (Di Nunzio et al, 2017).…”

Gamma Tocopherol Reduced Chemotherapeutic-Induced ROS in an Ovarian Granulosa Cell Line, But Not in Breast Cancer Cell Lines In Vitro

“…The four cell lines displayed different sensitivities to the cytotoxic and ROS-inducing activities of the test agents. Several factors affect cell line responses in vitro [62]. One factor is the cell doubling time, because some chemotherapeutics are phase-specific agents, which means that only cells that are passing through the relevant cell cycle phase when the drug is present are killed [63][64][65].…”