Potential human health effects of phycotoxins in marine bioaerosols
Lodewijks, E. (2017). Potential human health effects of phycotoxins in marine bioaerosols. MSc Thesis. Ghent University, Faculty Bioscience Engineering: Gent. 73 pp.
There is mounting evidence that suggests blue-green environments are beneficial for human health and wellbeing, however the causal factors involved remain uncertain. Moore (2015) recently proposed an immuno-regulatory mechanism to explain the ocean’s influence on human wellbeing, the biogenics hypothesis. He suggests that the wide variety of airborne biogenic compounds in natural environments (i.e. polyphenolics, antibiotics, algal and bacterial toxins) have an inhibiting effect on the activity of interconnected cell signalling networks, particularly PI3K/Akt/mTORC1. Dysregulation in the mTORC1 pathway has already been related to several pathological conditions. A source of marine bioaerosols are phycotoxins, toxins produced by microalgae. Adverse human health effects caused by exposure to aerosolised phycotoxins (i.e. brevetoxins and ovatoxins) have been reported during harmful algal blooms. However, no knowledge is available on the potentially positive health effects caused by exposure to low doses of these aerosolised toxins. To explore cytotoxicity, 43 h cell viability assays were conducted on two human epithelial lung cell lines using yessotoxin (YTX) and homoYTX (hYTX). Exposure of an alveolar epithelial cell line (A549) to the phycotoxins resulted in 43 h EC50 values of 4.34 ± 0.75 μg.L-1 (YTX) and2.48 ± 1.15 μg.L-1 (hYTX). Bronchial epithelial cells (BEAS-2B) exhibited a higher sensitivityto YTX (43 h EC50 = 3.40 ± 0.63 μg.L-1). Predicted environmental effect concentrations in the air were extrapolated from 43 h EC10 values. Bronchial tissue showed a higher sensitivity to YTX (81.52 ng.m-3) than alveolar tissue (90.68 μg.m-3) because the bronchial surface area in human lungs is smaller than the alveolar surface area. The bronchial concentrations are of the same magnitude as brevetoxin (PbTx-2) concentrations measured during harmful algal blooms. To examine the biogenics hypothesis, the response of the PI3K/Akt/mTORC1 pathway activity was investigated by assessing 43 h toxin treated lung cell lines with Western blotting. The effect of two toxins (i.e. YTX and hYTX) and a hYTX aerosol extract on the mTORC1 activity was tested with four biomarkers. The phosphorylation of these four downstream effectors of mTORC1 (i.e. S6RP, Akt, S6K and 4E-BP1) was used as a proxy for the pathway activity. When compared to the negative control, lower mTORC1 activities (p<0.05) were observed for all toxins with three biomarkers. One biomarker exhibited an upregulation of phosphorylation when treated with YTX for the BEAS-2B cell line. YTX and hYTX showed the ability to downregulate the mTORC1 activity in both cell lines. If this effect is also detectable at lower concentrations, during subsequent testing, these results are the first supporting the biogenics hypothesis.
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