Antioxidative responses in zebrafish liver exposed to sublethal doses Aphanizomenon flos-aquae DC-1 aphantoxins

• Aphantoxins induced significant lipid peroxidation in zebrafish liver.
• Oxidative stress markers increased in zebrafish liver following exposure to aphantoxins.
• Aphantoxins have the potential for hepatotoxicity in zebrafish.

Aphanizomenon flos-aquae secretes paralytic shellfish poisons (PSPs), termed aphantoxins, and endangers environmental and human health via eutrophication of water worldwide. Although the molecular mechanism of neuronal PSP toxicity has been well studied, several issues remain unresolved, notably the in vivo hepatic antioxidative responses to this neurotoxin. Aphantoxins extracted from a natural isolate of A. flos-aquae DC-1 were resolved by high performance liquid chromatography. The primary components were gonyautoxins 1 and 5 and neosaxitoxin. Zebrafish (Danio rerio) were treated intraperitoneally with either 5.3 or 7.61 (low and high doses, respectively) μg saxitoxin (STX) equivalents (eq)/kg of A. flos-aquae DC-1 aphantoxins. Antioxidative responses in zebrafish liver were examined at different timepoints 1–24 h post-exposure. Aphantoxin administration significantly enhanced hepatic malondialdehyde (MDA) content 1–12 h post-exposure, indicative of oxidative stress and lipid peroxidation. By contrast, levels of reduced glutathione (GSH) in zebrafish liver declined significantly after 3–24 h exposure, suggesting that GSH participates in MDA metabolism. A significant upregulation of the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) was observed, suggesting that aphantoxins induce lipid peroxidation in zebrafish liver and are likely to be hepatotoxic. Hepatic levels of MDA and GSH, and of the three enzymes (SOD, CAT, and GPx), therefore provide potential biomarkers for studying environmental exposure to aphantoxins/PSPs from cyanobacterial blooms.