Pro-apoptotic effects of nivalenol and deoxynivalenol trichothecenes in J774A.1 murine macrophages

Nivalenol (NIV) and deoxynivalenol (DON) are trichothecenes mycotoxins produced by Fusarium fungi that occur in cereal grains alone or in combination. Several studies have shown that exposure to high concentrations of these mycotoxins resulted in decreased cell proliferation; however, the molecular mechanism underlying their activities are still partially known. In this study, we evaluated the effects of NIV and DON, alone and in combination, on J7741.A macrophages viability. The results of the current study show that both NIV and DON (10-100 mu M) significantly stimulate apoptosis in J774A.1 macrophages in a concentration-dependent manner; in particular, NIV results a stronger pro-apoptotic effect than DON on cultured J774A.1 murine macrophages. No interactive effects were observed by exposing J774A.1 cells to both NIV and DON simultaneously. Pro-apoptotic activity induced by both mycotoxins seems to be essentially mediated by caspase-3 and is associated with a cell cycle blocking in G0/G1 phase. Moreover, our results show that NIV and DON are able to influence apoptotic pathway by ERK, pro-apoptotic protein Bax, caspase-3 and poly-ADP-ribose synthase (PARP), DNA repairing enzyme. (C) 2009 Elsevier Ireland Ltd. All rights reserved.