title: Morphological alterations and acetylcholinesterase and monoamine oxidase inhibition in liver of zebrafish exposed to Aphanizomenon flos-aquae DC-1 aphantoxins.
abstract: Aphanizomenon flos-aquae is a cyanobacterium that produces neurotoxins or paralytic shellfish poisons (PSPs) called aphantoxins, which present threats to environmental safety and human health via eutrophication of water bodies worldwide. Although the molecular mechanisms of this neurotoxin have been studied, many questions remain unsolved, including those relating to in vivo hepatic neurotransmitter inactivation, physiological detoxification and histological and ultrastructural alterations. Aphantoxins extracted from the natural strain of A. flos-aquae DC-1 were analyzed by high-performance liquid chromatography. The main components were gonyautoxins 1 and 5 (GTX1, GTX5) and neosaxitoxin (neoSTX), which comprised 34.04%, 21.28%, and 12.77% respectively. Zebrafish (Danio rerio) were exposed intraperitoneally to 5.3 or 7.61 μg STX equivalents (eq)/kg (low and high doses, respectively) of A. flos-aquae DC-1 aphantoxins. Morphological alterations and changes in neurotransmitter conduction functions of acetylcholinesterase (AChE) and monoamine oxidase (MAO) in zebrafish liver were detected at different time points 1-24h post-exposure. Aphantoxin significantly enhanced hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and histological and ultrastructural damage in zebrafish liver at 3-12 h post-exposure. Toxin exposure increased the reactive oxygen species content and reduced total antioxidative capacity in zebrafish liver, suggesting oxidative stress. AChE and MAO activities were significantly inhibited, suggesting neurotransmitter inactivation/conduction function abnormalities in zebrafish liver. All alterations were dose- and time-dependent. Overall, the results indicate that aphantoxins/PSPs induce oxidative stress through inhibition of AChE and MAO activities, leading to neurotoxicity in zebrafish liver. The above parameters may be useful as bioindicators for investigating aphantoxins/PSPs and cyanobacterial blooms in nature.
authors.affiliation: Department of Lifescience and Biotechnology, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070, PR China. Electronic address: deluzh@163.com.
authors.forename: De Lu
authors.initials: DL
authors.lastname: Zhang
authors.affiliation: College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072, PR China. Electronic address: cxhu@ihb.ac.cn.
authors.forename: Chun Xiang
authors.initials: CX
authors.lastname: Hu
authors.affiliation: Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072, PR China.
authors.forename: Gao Hong
authors.initials: GH
authors.lastname: Wang
authors.affiliation: Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072, PR China.
authors.forename: Dun Hai
authors.initials: DH
authors.lastname: Li
authors.affiliation: Key Laboratory of Algal Biology, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072, PR China.
authors.forename: Yong Ding
authors.initials: YD
authors.lastname: Liu
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D046890:Aphanizomenon / Q000737:chemistry; D001427:Bacterial Toxins / Q000737:chemistry / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008387:Marine Toxins / Q000737:chemistry / Q000633:toxicity*; D008995:Monoamine Oxidase / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D012530:Saxitoxin / Q000031:analogs & derivatives / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000502:physiology*
chemical_list: D001427:Bacterial Toxins; D008387:Marine Toxins; D014874:Water Pollutants, Chemical; D012530:Saxitoxin; C034902:neosaxitoxin; C034321:aphantoxin; C013007:gonyautoxins; D008995:Monoamine Oxidase; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; Cyanobacterial neurotoxin; Monoamine oxidase; Morphological alteration; Neurotoxicity; Zebrafish liver