Department of Orthopedagogy and Physical Therapy, Ternopil V. Hnatiuk National Pedagogical University, Ternopil, Ukraine; Department of Marine Biology, Institute for Biological Sciences, University of Rostock, Rostock, Germany.
Department of Orthopedagogy and Physical Therapy, Ternopil V. Hnatiuk National Pedagogical University, Ternopil, Ukraine.
Water Res. 2021 Apr 15;194:116923. doi: 10.1016/j.watres.2021.116923. Epub 2021 Feb 11.
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 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.
全球范围内蓝藻水华的增加带来了环境和健康威胁。尽管缺乏已知毒性代谢物的合成，但一些蓝藻菌株仍具有毒性，这些毒性的机制尚不清楚。在这里，我们研究了来自中欧的非柱孢藻毒素和非微囊藻毒素产生的束丝藻和裂须藻对暴露于其提取物 14 天的斑马鱼的毒性。毒理学筛选显示，在检查的提取物中存在鱼腥藻肽，而缺乏anatoxin-a、β-甲基氨基-L-丙氨酸或石房蛤毒素。将这些反应与 20μg/L 的常见蓝藻毒素柱孢藻毒素（CYN）和微囊藻-LR（MC-LR）进行了比较。使用靶向转录组学检测了参与细胞凋亡（caspase 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）、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）的标记基因的表达。在肝脏中测量了细胞应激和毒性生物标志物（氧化损伤、抗氧化酶、巯基池状态和乳酸脱氢酶活性），并在大脑中测定了乙酰胆碱酯酶活性作为神经毒性的指标。从三种不产生已知蓝藻毒素的蓝藻菌株中提取的提取物在斑马鱼中引起了明显的毒性，生物标志物谱表明，从这些菌株中提取的生物活性化合物与纯化的蓝藻毒素之间的毒性机制不同。所有研究的蓝藻提取物和纯化的蓝藻毒素均诱导了氧化应激和神经毒性，下调了 Nrf2 和 CYP26B1，破坏了磷酸化/去磷酸化过程以及肌动蛋白/微管蛋白细胞骨架，并上调了肝脏中的细胞凋亡活性。与 CYN 和 MC-LR 不同，中欧束丝藻和裂须藻菌株没有表现出遗传毒性。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学后果。
