Cellular detoxification of Fusarium mycotoxins

Worldwide many species in the genus Fusarium are contaminants of cereal plants. Some of the Fusarial secondary metabolites are known to be harmful to animals and human, because they may cause changes in haematological, biochemical and immunological indices. While reports about acute or chronic intoxication in animals caused by the cyclohexadepsipeptides beauvericin and enniatins are not available, moniliformin has been shown to be acutely toxic for various animal species, and is also a suspected cause of Keshan disease. In vitro beauvericin and enniatins are reported to have cytotoxic, antibiotic, hypolipidaemic and ionophoric activity. The latter property leads to intracellular ionic imbalance, resulting in decreased contractility, shortening of action potential and depolarization of resting membrane potential. The cyclohexadepsipeptides show similar effects concerning channel-forming properties, cell homoestasis and action on isolated guinea-pig heart and smooth muscle preparations, but significantly differ in ion selectivity, single channel current kinetics, potential-dependence and onset of action. Moniliformin, concomitantly detected in cereal probes, has cytotoxic and genotoxic effects, and might interfere with the cytotoxic effects of cyclohexadepsipeptides. It especially affects cardiac metabolism and tissue, but did not show significant effects on single channel currents. Unspecific and interindividual symptoms of mycotoxicosis raise the question whether sensibility might differ between individuals/cells. In preliminary experiments we found that the effects of the cyclohexadepsipeptides on cell homoestasis can be reversed by addition of ATP, i.e. cytotoxicity can be regulated by ATP consuming processes such as ion pumps or ABC-transporters. In principle one or both of the two pathways may contribute to the observed ATP-consumption. Thus we aim to identify the discussed involvement of ABC-transporters in Fusarium mycotoxin elimination. This aspect is of interest regarding i) which ABC-transporters are involved in a distinct Fusarium toxin elimination, thus influencing cell toxicity of the secondary metabolites, ii) the role of ABC-transporters in protection of the human body from the toxic impact of mycotoxins, iii) whether the cocktail of mycotoxins is augmenting or diminishing cell toxicity, and iv) whether such mycotoxins or derivatives serve as inhibitors of the multi-drug resistance in order to serve as chemotherapy remedy. The data will contribute to a better risk assessment of these secondary metabolites to feed and food.

Worldwide many species in the genus Fusarium are contaminants of cereal plants. Some of the Fusarial secondary metabolites are known to be harmful to animals and human, because they may cause changes in haematological, biochemical and immunological indices. While reports about acute or chronic intoxication in animals caused by the cyclohexadepsipeptides beauvericin and enniatins are not available, moniliformin has been shown to be acutely toxic for various animal species, and is also a suspected cause of Keshan disease. In vitro beauvericin and enniatins are reported to have cytotoxic, antibiotic, hypolipidaemic and ionophoric activity. The latter property leads to intracellular ionic imbalance, resulting in decreased contractility, shortening of action potential and depolarization of resting membrane potential. The cyclohexadepsipeptides show similar effects concerning channel-forming properties, cell homoestasis and action on isolated guinea-pig heart and smooth muscle preparations, but significantly differ in ion selectivity, single channel current kinetics, potential-dependence and onset of action. Moniliformin, concomitantly detected in cereal probes, has cytotoxic and genotoxic effects, and might interfere with the cytotoxic effects of cyclohexadepsipeptides. It especially affects cardiac metabolism and tissue, but did not show significant effects on single channel currents. Unspecific and interindividual symptoms of mycotoxicosis raise the question whether sensibility might differ between individuals/cells. In preliminary experiments we found that the effects of the cyclohexadepsipeptides on cell homoestasis can be reversed by addition of ATP, i.e. cytotoxicity can be regulated by ATP consuming processes such as ion pumps or ABC-transporters. In principle one or both of the two pathways may contribute to the observed ATP-consumption. Thus we aim to identify the discussed involvement of ABC-transporters in Fusarium mycotoxin elimination. This aspect is of interest regarding i) which ABC-transporters are involved in a distinct Fusarium toxin elimination, thus influencing cell toxicity of the secondary metabolites, ii) the role of ABC-transporters in protection of the human body from the toxic impact of mycotoxins, iii) whether the cocktail of mycotoxins is augmenting or diminishing cell toxicity, and iv) whether such mycotoxins or derivatives serve as inhibitors of the multi-drug resistance in order to serve as chemotherapy remedy. The data will contribute to a better risk assessment of these secondary metabolites to feed and food.