Toxic effects of palmitoyl-, oleoyl-, and linoleoyl-fumonisin B1 derivatives on zebrafish embryos and their interactions with serum albumin

Abstract

Acyl derivatives of the mycotoxin fumonisin B1 (FB1) occur in naturally infected grains and can be formed during certain food processing steps and/or as in vivo metabolites of the parent mycotoxin. The toxicity of N-acyl-FB1 metabolites is considerably higher compared to FB1; however, their toxic impacts and molecular interactions are barely characterized. To get a better insight into the structure-related and time-dependent toxic actions of acyl-FB1 derivatives, the effects of N-palmitoyl-, N-oleoyl-, N-linoleoyl-, 5-O-palmitoyl-, 5-O-oleoyl-, and 5-O-linoleoyl-FB1 were examined on zebrafish embryos. Furthermore, the interactions of these metabolites with human serum albumin (HSA) were investigated using fluorescence spectroscopy, isothermal titration calorimetry, and ultrafiltration. Our results underline the high in vivo toxicity of N-acyl-FB1 derivatives (LC₅₀ = 4–18 μM; 120 h), followed by 5-O-acyl-FB1 (LC₅₀ = 22–38 μM; 120 h) metabolites then FB1. Depending on the fatty acid component, the toxic potency and the time-dependent impacts showed large variations. N-palmitoyl-FB1 proved to be the most toxic derivative, causing high mortality at low micromolar levels even after 24 h exposure. Acyl-FB1 metabolites bind to HSA with high affinity (logK = 5.4–6.4), most of them occupy more binding sites on the protein. Interestingly, fatty acids, N-acyl-FB1 and 5-O-acyl-FB1 derivatives exerted different modulatory effects on the albumin binding of Site I and/or Site II markers examined. Our data demonstrate the similarities and differences regarding the toxic actions and the albumin binding properties of certain N-acyl- and 5-O-acyl-FB1 derivatives, and draw the attention to these barely examined mycotoxin metabolites.