Rangel Marisa, Martins Joyce C G, Garcia Angélica Nunes, Conserva Geanne A A, Costa-Neves Adriana, Sant'Anna Célia Leite, de Carvalho Luciana Retz
Immunopathology Laboratory, Butantan Institute, Av. Vital Brasil, 1500, Sao Paulo SP 05503-900, Brazil.
Phycology Section, Institute of Botany, Av. Miguel Stéfano, 3687, Sao Paulo SP 04301-902, Brazil.
Mar Drugs. 2014 Jan 22;12(1):508-24. doi: 10.3390/md12010508.
Cyanobacteria are common members of the freshwater microbiota in lakes and drinking water reservoirs, and are responsible for several cases of human intoxications in Brazil. Pseudanabaena galeata and Geitlerinema splendidum are examples of the toxic species that are very frequently found in reservoirs in Sao Paulo, which is the most densely populated area in Brazil. In the search for toxic strains collected from water reservoirs and maintained in the Cyanobacterial Culture Collection (CCIBt) of the Institute of Botany of Brazil, the acetic acid extracts (AE) of P. galeata CCIBt 3082 and G. splendidum CCIBt 3223 were analyzed by planar chromatography, which indicated the absence of cyanotoxins. Animal tests were then carried out, and both extracts were found to induce toxic effects in mice when administered intraperitoneally. The present study aimed to investigate whether the oral ingestion of the above mentioned cyanobacteria extracts would also induce toxic effects in mice. Necropsy and histopathological studies were conducted using tissue samples from the animals, which were euthanized one week after the administration of the extracts. The AE of P. galeata did not cause death but did induce transient symptoms, including eyebrow ptosis, straub tail, and pain. The euthanized animals presented hemorrhage in the liver, whereas the histological analysis showed disorganization of the hepatic parenchyma, necrosis, hyperemia, and proximity of the centrilobular vein in the liver. In addition, alterations in the convoluted tubules of the kidneys were observed, and the lungs were unaffected. The AE of G. splendidum caused only one death, and induced transient symptoms, such as dyspnea, paralysis, and pain, in the other mice. The necropsy of the euthanized mice showed hemorrhage in the lungs and liver. The lungs presented hemorrhagic focuses, alveolar collapse, and granulomatous foci. The liver presented hemorrhagic and enlarged sinusoids, hyperemia, proximity of the centrilobular vein, and disorganization of the hepatic parenchyma. Some areas also exhibited an inflammatory infiltrate and calcified tissue inside blood vessels. Necrosis and rupture of the convoluted tubule cells were observed in the kidneys. Further analysis of the both extracts indicated the lack of hemolytic activity, and the presence of two unknown anti-AChE substances in the AE of G. splendidum. Thus, P. galeata and G. splendidum are producers of novel toxins that affect mammals when administered orally.
蓝藻是湖泊和饮用水水库中淡水微生物群的常见成员,在巴西曾导致多起人类中毒事件。盖氏伪鱼腥藻和灿烂鞘丝藻是圣保罗水库中经常发现的有毒物种的例子,圣保罗是巴西人口最密集的地区。在从水库收集并保存在巴西植物研究所蓝藻培养物保藏中心(CCIBt)的有毒菌株的研究中,通过平面色谱法分析了盖氏伪鱼腥藻CCIBt 3082和灿烂鞘丝藻CCIBt 3223的乙酸提取物(AE),结果表明不存在蓝藻毒素。随后进行了动物试验,发现两种提取物腹腔注射时均能在小鼠中诱导毒性作用。本研究旨在调查口服上述蓝藻提取物是否也会在小鼠中诱导毒性作用。使用给药提取物一周后安乐死的动物的组织样本进行尸检和组织病理学研究。盖氏伪鱼腥藻AE未导致死亡,但确实诱发了短暂症状,包括眉下垂、弓背尾和疼痛。安乐死的动物肝脏出现出血,而组织学分析显示肝实质紊乱、坏死、充血以及肝小叶中央静脉靠近。此外,观察到肾脏曲小管有改变,而肺部未受影响。灿烂鞘丝藻AE仅导致一例死亡,并在其他小鼠中诱发了短暂症状,如呼吸困难、麻痹和疼痛。安乐死小鼠的尸检显示肺和肝出血。肺出现出血灶、肺泡塌陷和肉芽肿灶。肝脏出现出血性和扩张的血窦、充血、肝小叶中央静脉靠近以及肝实质紊乱。一些区域还表现出血管内炎性浸润和钙化组织。在肾脏中观察到曲小管细胞坏死和破裂。对两种提取物的进一步分析表明缺乏溶血活性,并且灿烂鞘丝藻AE中存在两种未知的抗乙酰胆碱酯酶物质。因此,盖氏伪鱼腥藻和灿烂鞘丝藻是新型毒素的生产者,口服给药时会影响哺乳动物。