A módosított, a mátrixhoz kötött és intakt mikotoxinok egységes fogalomrendszere és a mátrixhoz kötött mikotoxinok alternatív meghatározása

Az egészséges szervezet a mikotoxinok jelentős részét képes átalakítani. Néhány mikotoxin eredeti kémiai formája megváltozhat a máj xenobiotikum-transzfor- máló enzimrendszere, ill. az intestinalis mikrobiota által, de már keletkezésük helyén, a növényi szervezetben vagy akár a penészgomba által is átalakulhatnak. Ezen túlmenően a legkülönfélébb kémiai hatások is szerepet játszhatnak az eredeti szerkezet megváltoztatásában. Ennek során a kiindulási molekulánál toxikusabb, biológiailag aktívabb vegyületek is keletkezhetnek. A rejtett (kötött) mikotoxinok kérdésköre viszonylag új keletű. A nem egyértelműen és következetesen használt fogalmak tisztázására 2014-ben új, szisztematikus definíciórendszert dolgoztak ki, amely szerint négy hierarchikus szintre osztották a mikotoxino- kat kialakulásuk szerint. Rövid áttekintésében a szerző ezt a fogalomrendszert ismerteti számos példával bemutatva, ill. egy alternatív módszert ismertet a mátrixhoz kötött mikotoxinok analízisének előkészítésére. SUMMARY The healthy organism is able to transform a relatively high proportion of mycotoxins. The original molecular form of some mycotoxins may be altered via the enzymatic xenobiotic transformation ability of the liver, or even by the intestinal microbiota, but in some instances as early as the site of production by the mould or in the host plant they may be transformed, as well. Moreover, divergent chemical effects may play a role in the modification of the original chemical form. Along this process, the emerging new molecules can be more toxic and biologically more active than the parent compound. The hidden (bound) mycotoxin theory is rather new. For the clarification of the erroneously and unequivocally used terminology in the year 2014, a new, systematic definition criterion has been worked out, in which mycotoxins are classified into four hierarchic levels, based on their formation. This mini review introduces this classification system with numerous examples and shows alternative method for the prepara- tion of samples before analysis of matrix associated mycotoxins

Acute hepatic effects of low-dose fumonisin b1 In rats

Adult male Wistar rats were enrolled in a study to test the acute hepatic effects of 50 mg/kg fumonisin B1 in feed for 5 days. Fumonisin B1 depressed growth and feed intake, and absolute and relative liver weight showed a significant increase. The proportions of C17:0, C18:3 n3, C22:5 n3 and C22:6 n3 fatty acids decreased in the hepatic phospholipid fraction. All proportional decreases modified the hepatocellular membrane lipids into a more rigid state. The fatty acid profile modifications were partly compensated for by endogenous glutathione (preventing the formation of conjugated dienes and trienes as initial phase lipid peroxidation indicators), while the enzymatic antioxidant defence system (glutathione peroxidase) was unaltered. In contrast, hepatic malondialdehyde, the cytotoxic product of end-phase lipid peroxidation showed a concentration increase even after 5 days of feeding. The results indicate a rather strong and rapid hepatic effect of FB1, immediately impairing membrane phospholipids, even before the enzymatic antioxidant defence is activated

PRELIMINARY STRUCTURAL OPTIMIZATION OF SOME FUMONISIN METABOLITES BY DENSITY FUNCTIONAL THEORY CALCULATION

Maize (Zea mays L.) is often contaminated with Fusarium verticillioides. This harmful fungus produces fumonisins as secondary metabolites. These fumonisins can appear both free and hidden form in planta. The hidden form is usually bound covalently to cereal starch. From the hidden fumonisins, during enzymatic degradation, glycosides are formed, and the fumonisin is further decomposed during a de-esterification step. In this short communication some preliminary DFT calculated structural results which could be useful in the future to help to understand the van der Waals force controlled molecular interactions between these kinds of mycotoxin molecules and enzymes are demonstrated

Rabbits in Mycotoxin Research at Kaposvár University

In toxicity testing a lot of animals have been used as models with rodents being the most frequently used due to their small size and inexpensive purchase. Rabbits are large enough to permit easy handling and at the same time to facilitate easy blood and semen collection as well as other more intrusive practices like embryo transfer. Thus rabbits have been used in many studies on developmental and reproductive toxicity. Mycotoxin research is another field in which rabbits have been the animal of choice. Mycotoxins are the secondary metabolites of fungi which can cause a series of syndromes and health implications to both animals and humans. Rabbits are highly susceptible to aflatoxin B1 (AFB1). Ochratoxin A (OTA) can exert teratogenic effects whereas fumonisins can cause renal or liver toxicity to rabbits. In Kaposvár University both single (FB1, T-2, DON) and combined (FB1+T-2, DON+ZEA and FB1+DON+ZEA) experiments have been conducted. T-2 is the most studied mycotoxin and the No observed Adverse Effect Level (NOAEL) has been determined in rabbit bucks. The effect of FB1 has also been studied confirming the renal toxicity in pregnant rabbit does and the foetuses. ZEA has also been studied in combination with only DON or FB1 and DON. The effect of DON in concentration twice as much as the guidance value set by the European Commision for complementary and complete feedstuffs; rabbits were not severely affected. The two targets were the liver (altered morphology) and the immune system with no negative secondary effect

Oral administration of fumonisin B1 and T-2 individually and in combination affects hepatic total and mitochondrial membrane lipid profile of rabbits

Weaned rabbits were fed diets contaminated with 2 mg/kg diet T-2 toxin alone, or 10 mg/kg diet fumonisin B1 (FB1) alone, and both toxins in combination (2+10 mg / kg, resp.), as compared to a toxin free control diet. Samplings were performed after 4 weeks (blood and liver). Bodyweight of T-2-fed group was lower after 4 weeks; the liver weight was increased dramatically (3-fold of control). Liver total phospholipids (PL) provided slight alterations in the fatty acid (FA) composition; all three toxin treated groups showed decrease in palmitoleic acid (C16:1 n7) proportion. In the liver mitochondrial PL FA composition margaric acid (C17:0) proportion decreased in the separated toxin treatments, compared to the combined setting. Oleic acid (C18:1 n9) proportion was increased and arachidonic acid (C20:4 n6) was decreased in the by FB1-treated group, while docosapentaenoic acid (C22:5 n3) was decreased in the separated treatments. The total monounsaturation was significantly higher in the FB1 group’s mitochondrial PL FA profile. After 4 weeks, all toxin treatments decreased the blood plasma reduced glutathione and glutathione peroxidase activity, and FB1 increased the plasma sphinganine/sphingosine ratio. Both mycotoxins seem to cross the hepatocellular and the hepatic mitochondrial membrane, without drastic membrane disruption, as assessed from the PL FA composition, but inducing detectable lipid peroxidation

Preliminary results on the interactive effects of deoxynivalenol, zearalenone and fumonisin B1 on porcine lymphocytes

Fusarium mycotoxins, such as fumonisin B1 (FB1), deoxynivalenol (DON) and zearalenone (ZEN), frequently co-occur in feed raw materials and their presence is ubiquitous. The aims of this study were to determine the concentration that inhibits cell viability by 50% (IC50 values) for each mycotoxin (after 24, 48 and 72 h) and to investigate their combined effects in binary (DON + ZEN: DZ, DON + FB1: DF, FB1 + ZEN: FZ) and ternary (DFZ) mixtures using cyto- and genotoxicity on porcine lymphocytes as endpoints. The potency of cytotoxicity of the three toxins in an increasing order was FB1 1 (50% viability was reached only after 72 h). The main interaction observed was antagonism regarding cytotoxicity. Lower and higher sets of concentrations were used for the genotoxicity (comet assay) experiments. When lower concentrations were used, antagonism was again the main interaction observed. However, at higher concentrations an antagonism was confirmed only for DFZ, whereas for DZ and FZ a synergism was observed. Interactions of DF were inconsistent in different exposure periods in both series of experiments. Further studies with additional endpoints should be performed (e.g. DNA fragmentation, protein synthesis) in order to elucidate the mechanisms underlying the interactions observed

Fumonisin B1 exposure increases Hsp70 expression in the lung and kidney of rats without inducing significant oxidative stress

The objective of this experiment was to determine whether fumonisin B1 (FB1) added to the diet of rats in a dose of 50 mg/kg changes the production of heat shock protein 70 (Hsp70) in the lungs and kidney of rats. We also studied the effect of this mycotoxin on the antioxidant system of the body. Mature (8 weeks old) male Wistar Crl:WI BR rats (n = 6/group) were fed the toxin-containing diet for 5 days. FB1 resulted in a 7% body weight reduction without significantly changing the feed intake. Western blot analysis of the lungs and kidney demonstrated a substantial (1.4-fold and 1.8-fold, respectively) increase in Hsp70 expression. Alterations could not be detected in the clinical chemical parameters (total protein, albumin, total cholesterol, glucose, creatinine and urea concentrations, and aspartate aminotransferase activity). There was no statistically significant change in malondialdehyde concentrations and the measured antioxidant parameters (the amount of reduced glutathione, GSH and glutathione peroxidase activity, GPx) in the blood plasma, lung and kidney tissue. Thus, it can be concluded that FB1 did not induce oxidative stress in the lungs and kidney, but increased Hsp70 production