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Alternariol is a mycotoxin produced by Alternaria spp. relevant to the food safety area due to its abundance in certain foods. The shortage of data on its toxicology, also as a part of chemical mixtures, prevents setting regulation to limit its abundance in food. To extend knowledge on the possible mechanisms underpinning alternariol toxicology in chemical mixtures, this work assessed the effects of urolithin C, a structurally related gut ellagitannin-derived metabolite, on its absorption and phase II metabolism in a monolayer of Caco-2 cells. A computational study was also used to provide a mechanistic explanation for the results obtained. Urolithin C influenced transport and phase II metabolism of alternariol with a late reduction of transport to the basolateral compartment. Moreover, it caused an early effect in terms of accumulation of alternariol glucuronides in the basolateral compartment, followed by a late reduction of glucuronides in both compartments. Concerning alternariol sulfates, the data collected pointed to a possible competition of urolithin C for the sulfotransferases resulting in a reduced production of alternariol sulfates. Our results provide a compelling line-of-evidence pointing to the need to systematically tackle the evaluation of mycotoxin toxicity in the context of chemical mixture.
Francesco Crudo; Amelia Barilli; Pedro Mena; Bianca Maria Rotoli; Daniele Del Rio; Chiara Dall’Asta; Luca Dellafiora. An in vitro study on the transport and phase II metabolism of the mycotoxin alternariol in combination with the structurally related gut microbial metabolite urolithin C. Toxicology Letters 2021, 340, 15 -22.
AMA StyleFrancesco Crudo, Amelia Barilli, Pedro Mena, Bianca Maria Rotoli, Daniele Del Rio, Chiara Dall’Asta, Luca Dellafiora. An in vitro study on the transport and phase II metabolism of the mycotoxin alternariol in combination with the structurally related gut microbial metabolite urolithin C. Toxicology Letters. 2021; 340 ():15-22.
Chicago/Turabian StyleFrancesco Crudo; Amelia Barilli; Pedro Mena; Bianca Maria Rotoli; Daniele Del Rio; Chiara Dall’Asta; Luca Dellafiora. 2021. "An in vitro study on the transport and phase II metabolism of the mycotoxin alternariol in combination with the structurally related gut microbial metabolite urolithin C." Toxicology Letters 340, no. : 15-22.
Molds of the genus Alternaria produce several mycotoxins, some of which may pose a threat for health due to their genotoxicity. Due to the lack of adequate toxicological and occurrence data, they are currently not regulated. Interactions between mycotoxins, gut microbiota and food constituents might occur after food ingestion, modifying the bioavailability and, therefore, overall toxicity of mycotoxins. The present work aimed to investigate the impact of in vitro short-term fecal incubation on the in vitro DNA-damaging effects exerted by 5 µg/mL of an Alternaria alternata extract, containing, among others, 15 nM alternariol, 12 nM alternariol monomethyl ether, 241 nM altertoxin II and 301 nM stemphyltoxin III, all of which are known as genotoxic. The involvement of microorganisms, undigested food constituents and soluble substances of human fecal samples in modifying the composition and the genotoxicity of the extract was investigated through the application of LC–MS/MS analysis and comet assays in HT-29 cells. Results showed that the potential of the mycotoxins to induce DNA strand breaks was almost completely quenched, even before anaerobic incubation, by contact with the different fractions of the fecal samples, while the potency to induce formamidopyrimidine DNA glycosylase (FPG)-sensitive sites was only slightly reduced. These effects were in line with a reduction of mycotoxin concentrations found in samples analyzed by LC–MS/MS. Although a direct correlation between the metabolic activity of the gut microbiota and modifications in mycotoxin contents was not clearly observed, adsorptive phenomena to bacterial cells and to undigested food constituents might explain the observed modifications.
Francesco Crudo; Georg Aichinger; Jovana Mihajlovic; Luca Dellafiora; Elisabeth Varga; Hannes Puntscher; Benedikt Warth; Chiara Dall'Asta; David Berry; Doris Marko. Gut microbiota and undigested food constituents modify toxin composition and suppress the genotoxicity of a naturally occurring mixture of Alternaria toxins in vitro. Archives of Toxicology 2020, 94, 3541 -3552.
AMA StyleFrancesco Crudo, Georg Aichinger, Jovana Mihajlovic, Luca Dellafiora, Elisabeth Varga, Hannes Puntscher, Benedikt Warth, Chiara Dall'Asta, David Berry, Doris Marko. Gut microbiota and undigested food constituents modify toxin composition and suppress the genotoxicity of a naturally occurring mixture of Alternaria toxins in vitro. Archives of Toxicology. 2020; 94 (10):3541-3552.
Chicago/Turabian StyleFrancesco Crudo; Georg Aichinger; Jovana Mihajlovic; Luca Dellafiora; Elisabeth Varga; Hannes Puntscher; Benedikt Warth; Chiara Dall'Asta; David Berry; Doris Marko. 2020. "Gut microbiota and undigested food constituents modify toxin composition and suppress the genotoxicity of a naturally occurring mixture of Alternaria toxins in vitro." Archives of Toxicology 94, no. 10: 3541-3552.
Mycotoxins are low-molecular weight compounds produced by diverse genera of molds that may contaminate food and feed threatening the health of humans and animals. Recent findings underline the importance of studying the combined occurrence of multiple mycotoxins and the relevance of assessing the toxicity their simultaneous exposure may cause in living organisms. In this context, for the first time, this work has critically reviewed the most relevant data concerning the occurrence and toxicity of mycotoxins produced by Alternaria spp., which are among the most important emerging risks to be assessed in food safety, alone or in combination with other mycotoxins and bioactive food constituents. According to the literature covered, multiple Alternaria mycotoxins may often occur simultaneously in contaminated food, along with several other mycotoxins and food bioactives inherently present in the studied matrices. Although the toxicity of combinations naturally found in food has been rarely assessed experimentally, the data collected so far, clearly point out that chemical mixtures may differ in their toxicity compared to the effect of toxins tested individually. The data presented here may provide a solid foothold to better support the risk assessment of Alternaria mycotoxins highlighting the actual role of chemical mixtures on influencing their toxicity.
Francesco Crudo; Elisabeth Varga; Georg Aichinger; Gianni Galaverna; Doris Marko; Chiara Dall'Asta; Luca Dellafiora. Co-Occurrence and Combinatory Effects of Alternaria Mycotoxins and other Xenobiotics of Food Origin: Current Scenario and Future Perspectives. Toxins 2019, 11, 640 .
AMA StyleFrancesco Crudo, Elisabeth Varga, Georg Aichinger, Gianni Galaverna, Doris Marko, Chiara Dall'Asta, Luca Dellafiora. Co-Occurrence and Combinatory Effects of Alternaria Mycotoxins and other Xenobiotics of Food Origin: Current Scenario and Future Perspectives. Toxins. 2019; 11 (11):640.
Chicago/Turabian StyleFrancesco Crudo; Elisabeth Varga; Georg Aichinger; Gianni Galaverna; Doris Marko; Chiara Dall'Asta; Luca Dellafiora. 2019. "Co-Occurrence and Combinatory Effects of Alternaria Mycotoxins and other Xenobiotics of Food Origin: Current Scenario and Future Perspectives." Toxins 11, no. 11: 640.