Adduction to arginine detoxifies aflatoxin B1 by eliminating genotoxicity and altering in vitro toxicokinetic profiles
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Blake R. Rushing1 and Mustafa I. Selim1
1Department of Pharmacology and Toxicology, East Carolina University, Brody School of Medicine, Greenville, NC, 27834, USA
Blake R. Rushing, email: [email protected]
Keywords: aflatoxin; adduction; genotoxicity; ADME; mass spectrometry
Received: August 20, 2017 Accepted: November 26, 2017 Published: December 17, 2017
Aflatoxin B1 (AFB1), a class 1 carcinogen and prominent food contaminant, is highly linked to the development of hepatocellular carcinoma (HCC) and plays a causative role in a large portion of global HCC cases. We have demonstrated that a mixture of common organic acids (citric and phosphoric acid) along with arginine can eliminate >99% of AFB1 in solution as well as on corn kernels and convert it to the AFB2a-Arg adduct, acting as a potential detoxification process for contaminated foods. Evaluation of toxicokinetic changes after AFB2a-Arg formation show that the product is highly stable in biological fluids, is not metabolized by P450 enzymes, is highly plasma protein bound, has low lipid solubility, and has poor intestinal permeability/high intestinal efflux compared to AFB1. Ames’ test results show that at mutagenic concentrations of AFB1, AFB2a-Arg does not have any measurable mutagenic effect which was confirmed by DNA adduct identification by liquid chromatography-mass spectrometry. Evaluation in HepG2 and HepaRG cells showed that AFB2a-Arg did not cause any significant decreases in cell viability nor did it increase micronuclei formation when administered at toxic concentrations of AFB1. These results show that conversion of AFB1 to AFB2a-Arg is a potential strategy to detoxify contaminated foods.
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