The global increase in cyanobacterial blooms poses environmental and health threats. Selected cyanobacterial strains reveal toxicities despite a lack of synthesis of known toxic metabolites, and the mechanisms of these toxicities are not well understood. Here we investigated the toxicity of non-cylindrospermopsin and non-microcystin producing Aphanizomenon gracile and Raphidiopsis raciborskii of Central European origin to zebrafish exposed for 14 days to their extracts. Toxicological screening revealed the presence of anabaenopeptins and a lack of anatoxin-a, ß-methylamino-L-alanine or saxitoxins in examined extracts. The responses were compared to 20 μg L⁻¹ of common cyanobacterial toxins cylindrospermopsin (CYN) and microcystin-LR (MC-LR). The expression of the marker genes involved in apoptosis (caspase 3a and 3b, Bcl-2, BAX, p53, MAPK, Nrf2), DNA damage detection and repair (GADD45, RAD51, JUN, XPC), detoxification (CYP1A, CYP26, EPHX1), lipid metabolism (PPARa, FABP1, PLA2), phosphorylation/dephosphorylation (PPP6C, PPM1) and cytoskeleton (actin, tubulin) were examined using targeted transcriptomics. Cellular stress and toxicity biomarkers (oxidative injury, antioxidant enzymes, thiol pool status, and lactate dehydrogenase activity) were measured in the liver, and acetylcholinesterase activity was determined as an index of neurotoxicity in the brain. The extracts of three cyanobacterial strains that produce no known cyanotoxins caused marked toxicity in D. rerio, and the biomarker profiles indicate different toxic mechanisms between the bioactive compounds extracted from these strains and the purified cyanotoxins. All studied cyanobacterial extracts and purified cyanotoxins induced oxidative stress and neurotoxicity, downregulated Nrf2 and CYP26B1, disrupted phosphorylation/dephosphorylation processes and actin/tubulin cytoskeleton and upregulated apoptotic activity in the liver. The tested strains and purified toxins displayed distinctively different effects on lipid metabolism. Unlike CYN and MC-LR, the Central European strain of A. gracile and R. raciborskii did not reveal a genotoxic potential. These findings help to further understand the ecotoxicological consequences of toxic cyanobacterial blooms in freshwater ecosystems.

蓝藻水华的全球增加对环境和健康构成威胁。尽管缺乏已知毒性代谢产物的合成，但选定的蓝细菌菌株仍显示出毒性，并且对这些毒性的机理尚不十分了解。在这里，我们调查了非中环产非环孢菌素和非微囊藻毒素的Aphanizomenon graticile和Raphidiopsis raciborskii对中性斑马鱼的毒性，斑马鱼暴露了14天。毒理学筛查显示，受检提取物中存在ananaenopeptins，缺少anatoxin-a，ß-methylamino-L-丙氨酸或saxitoxins。将响应与20μgL ^-1进行比较常见的蓝藻毒素cylindrospermopsin（CYN）和微囊藻毒素-LR（MC-LR）。凋亡相关标志物基因的表达（胱天蛋白酶3a和3b，Bcl-2，BAX，p53，MAPK，Nrf2），DNA损伤检测和修复（GADD45，RAD51，JUN，XPC），解毒（CYP1A，CYP26，EPHX1） ），使用靶向转录组学检查脂质代谢（PPARa，FABP1，PLA2），磷酸化/去磷酸化（PPP6C，PPM1）和细胞骨架（肌动蛋白，微管蛋白）。在肝脏中测量细胞应激和毒性生物标志物（氧化损伤，抗氧化酶，硫醇池状态和乳酸脱氢酶活性），并确定乙酰胆碱酯酶活性作为大脑中神经毒性的指标。三种不产生已知蓝藻毒素的蓝细菌菌株的提取物在雷氏杜鹃中引起明显的毒性和，生物标志物概况表明从这些菌株提取的生物活性化合物与纯化的氰毒素之间的不同毒性机制。所有研究的蓝细菌提取物和纯化的蓝毒素诱导氧化应激和神经毒性，下调Nrf2和CYP26B1，破坏磷酸化/去磷酸化过程以及肌动蛋白/微管蛋白的细胞骨架，并上调肝脏的凋亡活性。测试的菌株和纯化的毒素对脂质代谢表现出明显不同的作用。与CYN和MC-LR不同，中欧的A. gracile和R. raciborskii菌株没有显示出遗传毒性。这些发现有助于进一步了解淡水生态系统中有毒蓝藻水华的生态毒理后果。