Abstract
Some mycotoxins such as beauvericin (BEA), ochratoxin A (OTA), and zearalenone (ZEA) can cross the blood brain barrier, which is why we tested the anti-inflammatory action of a pumpkin carotenoid extract (from the pulp) against these mycotoxins and their combinations (OTA+ZEA and OTA+ZEA+BEA) on a blood brain barrier model with co-cultured ECV304 and C6 cells using an untargeted metabolomic approach. The cells were added with mycotoxins at a concentration of 100 nmol/L per mycotoxin and pumpkin carotenoid extract at 500 nmol/L. For control we used only vehicle solvent (cell control) or vehicle solvent with pumpkin extract (extract control). After two hours of exposure, samples were analysed with HPLC-ESI-QTOF-MS. Metabolites were identified against the Metlin database. The proinflammatory arachidonic acid metabolite eoxin (14,15-LTE4) showed lower abundance in ZEA and BEA+OTA+ZEA-treated cultures that also received the pumpkin extract than in cultures that were not treated with the extract. Another marker of inflammation, prostaglandin D2-glycerol ester, was only found in cultures treated with OTA+ZEA and BEA+OTA+ZEA but not in the ones that were also treated with the pumpkin extract. Furthermore, the concentration of the pumpkin extract metabolite dihydromorelloflavone significantly decreased in the presence of mycotoxins. In conclusion, the pumpkin extract showed protective activity against cellular inflammation triggered by mycotoxins thanks to the properties pertinent to flavonoids contained in the pulp.
Highlights
Some mycotoxins such as beauvericin (BEA), ochratoxin A (OTA), and zearalenone (ZEA) can cross the blood brain barrier, which is why we tested the anti-inflammatory action of a pumpkin carotenoid extract against these mycotoxins and their combinations (OTA+ZEA and OTA+ZEA+BEA) on a blood brain barrier model with co-cultured ECV304 and C6 cells using an untargeted metabolomic approach
Considering that carotenoids have been evidenced to protect genes against oxidative action of mycotoxins [8,9,10,11,12] and are depleted in Alzheimer’s and Parkison’s disease [13, 14], the second aim our study was to establish if pumpkin extract protects against blood brain barrier (BBB) damage induced by BEA, OTA, and ZEA in differentiated human ECV304 cells applying the metabolomics approach, which provides an insight into how organisms interact with the environment [15]
In samples treated with pumpkin extract, only 9-docosene and dihydromorelloflavone were identified regardless of the mycotoxin used, but only dihydromorelloflavone was significantly less abundant in these samples than in positive control, while it was not found in samples not exposed to the extract
Summary
Some mycotoxins such as beauvericin (BEA), ochratoxin A (OTA), and zearalenone (ZEA) can cross the blood brain barrier, which is why we tested the anti-inflammatory action of a pumpkin carotenoid extract (from the pulp) against these mycotoxins and their combinations (OTA+ZEA and OTA+ZEA+BEA) on a blood brain barrier model with co-cultured ECV304 and C6 cells using an untargeted metabolomic approach. Considering that carotenoids have been evidenced to protect genes against oxidative action of mycotoxins [8,9,10,11,12] and are depleted in Alzheimer’s and Parkison’s disease [13, 14], the second aim our study was to establish if pumpkin extract protects against BBB damage induced by BEA, OTA, and ZEA in differentiated human ECV304 cells applying the metabolomics approach, which provides an insight into how organisms interact with the environment [15] It looks into metabolites (intermediates and end products of cellular processes) that mediate the body’s
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