The lipid-mediated hypothesis of fumonisin B1 toxicodynamics tested in model membranes

The disruption of lipidic metabolism was considered a good candidate to explain FB1 toxicity mechanism. In the present work we investigated molecular organizational changes induced by FB1-biomembrane interaction possibly involved in mycotoxic effects. FB1 was self-aggregated with a critical micellar concentration of 1.97 mM. FB1 (0-81.4 mu M), decreased in a dose-dependent manner, the fluorescence anisotropy of TMA-DPH (from 0.349 +/- 0.003 to 0.1720 +/- 0.0035) in dpPC bilayers, whilst no differences were registered with DPH. At 5.6 mu M in the subphase, FB1 increased the lateral surface pressure (pi) of a Langmuir film to an extent that depended on the monolayer composition (Delta pi(dpPC:DOTAP) (3:1) > Delta pi(dpPC:dpPA3:1) > Delta pi(dpPC)), the molecular packing (Delta pi decreased linearly as a function of the initial pi) and the subphase pH (Delta pi(pH 2.6) > Delta pi(pH 7.4) and maximal pi allowing the drug penetration pi(cut-off) was 34.3 and 27.7 mN/m at pH 2.63 and 7.4, respectively). FBI increased the surface potential of dpPC and dpPC:DOTAP monolayers and decreased that of dpPC:dpPA. This suggested that FBI acquired different orientations and/or foldings depending on the surface electrostatics and the toxin charge state. Moreover, FB1-lipid interactions were transduced into long-range effects at the mesoscopic level affecting the lipidic self-separated lateral domains shape and density. (C) 2008 Elsevier B.V. All rights reserved.