Article ID Journal Published Year Pages File Type
2599224 Toxicology Letters 2013 9 Pages PDF
Abstract

•Enniatins (ENs) A, A1, B and B1 are cytotoxic to Caco-2 cells.•ROS generation and LPO production are involved in ENs cytotoxicity.•ENs induced apoptosis and mitochondrial disruption in Caco-2 cells.•DNA damage was observed after ENs A and A1 exposure, and it is corroborated by the arrest of the cell cycle in G2/M phase.

The cytotoxic effects, the generation of reactive oxygen species (ROS) and lipid peroxidation (LPO) as well as the cell cycle disruption, the induction of apoptosis and changes in mitochondrial membrane potential (ΔΨm) as a function of increasing time have been determined in human colorectal adenocarcinoma (Caco-2) cells after exposure to enniatins (ENs) A, A1, B and B1. IC50 values obtained by the MTT and Neutral Red assay, after 24, 48 and 72 h of exposure ranged from 0.5 ± 0.1 to >15 μM. A significant increase (p ≤ 0.05) in ROS generation and LPO production, as determined by the fluorescent probe H2-DCFDA and TBARS method respectively, was observed for all mycotoxins tested at 3.0 μM concentration. The highest increase in ROS generation (2.6 fold higher than control) and LPO production (111%, as compared to control) was observed with EN A. Cell cycle was significantly arrested at G2/M phase after 24 h of exposure to EN A, A1, B1, whereas after 72 h of exposure an arrest in S phase was observed almost for all mycotoxins tested. Moreover, after 24 and 48 h of exposure, ENs increased the early apoptotic cells, whereas after 72 h of exposure necrosis was observed. In addition the loss of ΔΨm was produced on Caco-2 cells after ENs exposure. ENs A, A1, B and B1 cytotoxicity involved early ROS generation that induced LPO oxidative damage, apoptosis and necrosis via the mitochondrial pathway. ENs A, A1 and B1 induced DNA damage. However the same effects cannot be proposed for EN B. Further studies on the toxicological effects induced by ENs A, A1, B and B1 are needed.

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Life Sciences Environmental Science Health, Toxicology and Mutagenesis
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