Area of Toxicology, Faculty of Pharmacy, University of Sevilla, Profesor García González n2, 41012 Sevilla, Spain.
University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, Calea Mănăștur 3-5, 400372 Cluj-Napoca, Romania.
Toxins (Basel). 2020 May 26;12(6):348. doi: 10.3390/toxins12060348.
Cylindrospermopsin (CYN) and microcystins (MC) are cyanotoxins that can occur simultaneously in contaminated water and food. CYN/MC-LR mixtures previously investigated in vitro showed an induction of micronucleus (MN) formation only in the presence of the metabolic fraction S9. When this is the case, the European Food Safety Authority recommends a follow up to in vivo testing. Thus, rats were orally exposed to 7.5 + 75, 23.7 + 237, and 75 + 750 μg CYN/MC-LR/kg body weight (b.w.). The MN test in bone marrow was performed, and the standard and modified comet assays were carried out to measure DNA strand breaks or oxidative DNA damage in stomach, liver, and blood cells. The results revealed an increase in MN formation in bone marrow, at all the assayed doses. However, no DNA strand breaks nor oxidative DNA damage were induced, as shown in the comet assays. The histopathological study indicated alterations only in the highest dose group. Liver was the target organ showing fatty degeneration and necrotic hepatocytes in centrilobular areas, as well as a light mononuclear inflammatory periportal infiltrate. Additionally, the stomach had flaking epithelium and mild necrosis of epithelial cells. Therefore, the combined exposure to cyanotoxins may induce genotoxic and histopathological damage in vivo.
柱孢藻毒素 (CYN) 和微囊藻毒素 (MC) 是两种同时存在于污染水中和食物中的蓝藻毒素。先前在体外研究的 CYN/MC-LR 混合物仅在存在代谢部分 S9 的情况下才会诱导微核 (MN) 形成。在这种情况下，欧洲食品安全局建议进行后续的体内测试。因此，大鼠经口暴露于 7.5 + 75、23.7 + 237 和 75 + 750 μg CYN/MC-LR/kg 体重。进行了骨髓中的 MN 测试，并进行了标准和改良的彗星试验，以测量胃、肝和血细胞中的 DNA 链断裂或氧化 DNA 损伤。结果表明，在所有检测剂量下，骨髓中的 MN 形成均增加。然而，如彗星试验所示，未诱导 DNA 链断裂或氧化 DNA 损伤。组织病理学研究表明，仅在最高剂量组中出现改变。肝脏是靶器官，表现为中央小叶区的脂肪变性和坏死肝细胞，以及轻度单核炎性门脉周围浸润。此外，胃有剥落的上皮和上皮细胞的轻度坏死。因此，蓝藻毒素的联合暴露可能会导致体内的遗传毒性和组织病理学损伤。
