Department of Food Technology, Food Safety and Health, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium.
Laboratory of Food Analysis, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
Toxins (Basel). 2018 Jul 2;10(7):266. doi: 10.3390/toxins10070266.
The emetic syndrome of is a food intoxication caused by cereulide (CER) and manifested by emesis, nausea and in most severe cases with liver failure. While acute effects have been studied in the aftermath of food intoxication, an exposure to low doses of cereulide might cause unnoticed damages to the intestines and liver. The toxicity which relies on the mitochondrial dysfunction was assessed on Caco-2 and HepG2 cells after exposure of one, three and ten days to a range of low doses of cereulide. Oxygen consumption rate analyses were used to study the impact of low doses of CER on the bioenergetics functions of undifferentiated Caco-2 and HepG2 cells using Seahorse XF extracellular flux analyzer. Both Caco-2 and HepG2 cells experienced measurable mitochondrial impairment after prolonged exposure of 10 days to 0.25 nM of cereulide. Observed mitochondrial dysfunction was greatly reflected in reduction of maximal cell respiration. At 0.50 nM CER, mitochondrial respiration was almost completely shut down, especially in HepG2 cells. These results corresponded with a severe reduction in the amount of cells and an altered morphology, observed by microscopic examination of the cells. Accurate and robust quantification of basal respiration, ATP production, proton leak, maximal respiration, spare respiratory capacity, and non-mitochondrial respiration allowed better understanding of the effects of cereulide in underlying respiratory malfunctions in low-dose exposure.
呕吐毒素综合征是一种由玉米赤霉烯酮（CER）引起的食物中毒，表现为呕吐、恶心，在大多数严重情况下还伴有肝衰竭。虽然已经研究了食物中毒后的急性影响，但低剂量的玉米赤霉烯酮可能会对肠道和肝脏造成未被察觉的损害。这种依赖于线粒体功能障碍的毒性，在将 Caco-2 和 HepG2 细胞暴露于一系列低剂量玉米赤霉烯酮 1、3 和 10 天后，在细胞水平上进行了评估。使用 Seahorse XF 细胞外通量分析仪，通过氧消耗率分析研究低剂量 CER 对未分化 Caco-2 和 HepG2 细胞生物能学功能的影响。经过 10 天 0.25 nM 玉米赤霉烯酮的长时间暴露，Caco-2 和 HepG2 细胞都经历了可测量的线粒体损伤。观察到的线粒体功能障碍在最大细胞呼吸的减少中得到了很好的反映。在 0.50 nM CER 时，线粒体呼吸几乎完全关闭，尤其是在 HepG2 细胞中。这些结果与细胞数量的严重减少以及细胞形态的改变相对应，通过细胞的显微镜检查观察到了这些变化。基础呼吸、ATP 产生、质子泄漏、最大呼吸、备用呼吸能力和非线粒体呼吸的准确稳健定量，使我们能够更好地理解低剂量暴露下玉米赤霉烯酮在潜在呼吸功能障碍中的作用。
