Mycotoxins that chelate: a tool for probing toxin/metal interactions

Authors: Maragos, Chris; HOSSAIN, MD - Orise Fellow

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 11/8/2019
Publication Date: 11/8/2019
Citation: Maragos, C.M., Hossain, M.Z. 2019. Mycotoxins that chelate: a tool for probing toxin/metal interactions [abstract].

Interpretive Summary:

Technical Abstract: Certain toxic secondary metabolites of fungi (mycotoxins) chelate metals. In particular, ochratoxin A (OTA), citrinin (CIT), cyclopiazonic acid (CPA), kojic acid, and tenuazonic acid (TeA) are known chelators. These mycotoxins, which have a wide range of structures, also have widely different targets, including the liver, kidney, immune system, and the nervous system. OTA, CIT, CPA, and TeA are found in a variety of foods including cereal grains, meats and cheeses. Kojic acid is used in cosmetics as depigmentation agent. Certain of the lanthanide metals, such as terbium and europium, can fluoresce. This fluorescence is generally low but can be facilitated by interaction with molecules that transfer energy to the metal. This property has made europium and terbium useful as fluorescent probes of molecular interactions. Three of the chelating mycotoxins (OTA, CPA and TeA) are able to form complexes with terbium and europium. When such complexes form light can be absorbed by the toxin and transferred to the lanthanide, enhancing the fluorescence of the metal. The effect of OTA was minor. The relatively poor enhancement with OTA was likely caused by the loss of energy from “self-fluorescence”. However, both CPA and TeA were able to greatly enhance the fluorescence of lanthanides. Terbium (Tb3+) was the more effective of the two lanthanides. The influence of environmental parameters on the formation, and fluorescence from, the mycotoxin-lanthanide complexes was examined in detail. The type of solvent used, the water content, and pH were all important contributors to signal development. Optimal conditions consisted of 90% methanol with 10% aqueous buffer at pH 3-4. The development of model systems of TeA-Tb3+ and CPA-Tb3+ permitted an exploration of how other metals bind to these toxins. An assay was established wherein other metal cations (Cu2+, Al3+, Au3+, Fe3+, Co2+, Mn2+, Mg2+, Ca2+, Na+, K+) competed with Tb3+ for binding to the mycotoxins. Results indicated that both CPA and TeA interacted best with Cu2+. After Cu2+ the metals in oxidation state 3 generally disrupted the interaction better than metals in oxidation state two. The two metals in oxidation state one (Na+, K+) were essentially inactive. Because the inhibition of certain enzymes, such as sarco(endo)plasmic reticulum Ca2+-ATPase is suspected to involve chelation, an understanding of the relative affinity of TeA and CPA for metals may provide insights into the mechanism of action of these toxins.