Adduction to arginine detoxifies aflatoxin B1 by eliminating genotoxicity and altering in vitro toxicokinetic profiles

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Blake R.,Selim,Mustafa I. Rushing (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Aflatoxin B1 (AFB1), a class 1 carcinogen and prominent food contaminant,is highly linked to the development of hepatocellular carcinoma (HCC) and plays acausative role in a large portion of global HCC cases. We have demonstrated that amixture of common organic acids (citric and phosphoric acid) along with arginine caneliminate >99% of AFB1 in solution as well as on corn kernels and convert it to theAFB2a-Arg adduct, acting as a potential detoxification process for contaminated foods.Evaluation of toxicokinetic changes after AFB2a-Arg formation show that the productis highly stable in biological fluids, is not metabolized by P450 enzymes, is highlyplasma protein bound, has low lipid solubility, and has poor intestinal permeability/high intestinal efflux compared to AFB1. Ames" test results show that at mutagenicconcentrations of AFB1, AFB2a-Arg does not have any measurable mutagenic effectwhich was confirmed by DNA adduct identification by liquid chromatography-massspectrometry. Evaluation in HepG2 and HepaRG cells showed that AFB2a-Arg didnot cause any significant decreases in cell viability nor did it increase micronucleiformation when administered at toxic concentrations of AFB1. These results showthat conversion of AFB1 to AFB2a-Arg is a potential strategy to detoxify contaminatedfoods

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Language: English

Date: 2018

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