Citral presents cytotoxic and genotoxic effects in human cultured cells.

Citral, 3,7-dimethyl-2,6-octadien-1-al, one of the main components of the essential oils obtained from several plants, is used as a food additive and as a fragrance for detergents, cosmetics and other toiletries. The literature shows disparity regarding citral genotoxicity. Thus, the main objective of our work was to evaluate the genotoxic effects of citral in human cell cultures, HepG2 and leukocytes. Cytotoxicity assays (trypan blue and MTT) showed citral toxic effects in HepG2 cells (with metabolizing liver enzymes), which contrasted with the absence of toxicity in leukocytes. After citral exposure, both cell types did not demonstrate clastogenic/aneugenic effects in the micronucleus test. However, for the comet assay, citral exposure lead to significant genotoxic effects in both HepG2 (even to citral low concentrations) and leukocytes. The use of citral must be viewed with caution due to its ability to induce DNA damages, especially after being metabolized by cells with active liver enzymes.

Antioxidant and cytotoxic effects of crude extract, fractions and 4-nerolidylcathecol from aerial parts of Pothomorphe umbellata L. (Piperaceae).

The crude ethanolic extract from aerial parts of Pothomorphe umbellata L. (Piperaceae) and fractions obtained by partitions sequentially among water-methanol, methylene chloride, and ethyl acetate, as well as the major constituent, 4-nerolidylcatechol, were, respectively, evaluated and evidenced for antioxidant and cytotoxic effects through fluorometric microplate and microculture tetrazolium assays in HL-60 cells. The crude ethanolic extract demonstrated the preeminent antioxidant activity (IC50 = 1.2 µg/mL) against exogenous cytoplasmic reactive oxygen species, followed by the water-methanolic (IC50 = 4.5 µg/mL), methylene chloride (IC50 = 5.9 µg/mL), ethyl acetate (IC50 = 8.0 µg/mL), 4-nerolidylcatechol (IC50 = 8.6 µg/mL), and the sterol fractions (IC50 > 12.5 µg/mL). Vitamin C, the positive control used in this assay, presented IC50 value equivalent to 1.7 µg/mL. 4-Nerolidylcatechol (IC50 = 0.4 µg/mL) and methylene chloride fraction (IC50 = 2.3 µg/mL) presented considerable cytotoxicity probably because of the presence of an o-quinone, an auto-oxidation by product of the catechol. Polar compounds, present in the ethanol extract, appear to increase the solubility and stability of the major active constituent, acting synergistically with 4-nerolidylcatechol, improving its pharmacokinetic parameters and increasing significantly its antioxidant activity which, in turn, suggests that the aqueous-ethanolic extract, used in folklore medicine, is safe and effective.