Trichothecene synergism, additivity, and antagonism: The significance of the maximally quiescent ratio

Abstract

The interactive effect of the combinations of trichothecene mycotoxins often found in fungus infected plants, contaminated grain, and other biological systems is poorly understood. Growth inhibition of the yeast Kluyveromyces marxianus was used to measure the effects of HT-2 toxin, roridin A, and T-2 toxin as individual toxins or as binary mixtures. A value, the combination index, was derived which indicates the interactive effects of a binary mixture of toxins. The interaction is affected by the ratio of the individual toxins, and the percent inhibition of yeast growth. Generally the interaction of T-2 toxin and roridin A or T-2 toxin and HT-2 toxin changes from antagonistic when they cause a low percent inhibition of yeast growth to synergistic when they cause a high percent inhibition of yeast growth. Additionally, any two trichothecenes have a unique ratio, which we name the maximally quiescent ratio (or MQR), where there is the least change in the type and intensity of their interaction. The maximally quiescent ratio in this case has helped to define the nature of toxin interactions and could be used to provide insights into hormone, immune system, developmental, enzyme, and gene regulation, combined drug therapy, and the action of mixtures of natural or synthetic toxins, carcinogens, pesticides, and environmental pollutants.

Individual and combined cytotoxic effects of Fusarium toxins (deoxynivalenol, nivalenol, zearalenone and fumonisins B1) on swine jejunal epithelial cells

“…The interactive effect of DON and NIV found in the present study was in agreement with some previous in vitro studies on yeast growth (Madhyastha et al, 1994) and on DNA syntheses in L929 cells (Tajima et al, 2002), although some reported additivity of trichothecenes (Thuvander et al, 1999). A plausible explanation for such discrepancies could be differences in the ratios of trichothecenes in the mixture, or to differences in effect levels (Jones et al, 1995;Koshinsky and Khachatourians, 1992). The possible interaction between ZEA and FB1 was not fully elucidated in the current stage.…”

The phytotoxicity ofFusarium metabolites: An update since 1989

“…In in vitro studies testing the effect of multiple trichothecene exposure on fungi, there was evidence of interactive relationships between different toxins [47]. This is an important consideration, since F. graminearum, a strongly aggressive species against cereals, is capable of producing NIV, fusaranon-X, DON, 3-acetyldeoxynivalenol (3-ADON), as well as ZEA, depending on geographic location [33,48].…”

Implication of Utilizing Phytoestrogens Infested Fodder on Fertility and Histological Structure of Ovaries and Oviduct in Sow

“…Moulds on the floor can extend through continuity to the concrete feeding areas and thus come in contact with the combined fodder from pigs' alimentation. According to Koshinsky and Khachatourians (1992) the presence of fungi that produce toxins in animal food or the accommodating areas does not automatically imply toxicity. When more fungi are present, each of them can produce different mycotoxins and this combination can cause more adverse effects in comparison to only one mycotoxin because of the additive or synergic interaction.…”