Aerosolizable Marine Phycotoxins and Human Health Effects: In Vitro Support for the Biogenics Hypothesis

Abstract

Respiratory exposure to marine phycotoxins is of increasing concern. Inhalation of sea spray aerosols (SSAs), during harmful Karenia brevis and Ostreopsis ovata blooms induces respiratory distress among others. The biogenics hypothesis, however, suggests that regular airborne exposure to natural products is health promoting via a downregulation of the mechanistic target of rapamycin (mTOR) pathway. Until now, little scientific evidence supported this hypothesis. The current explorative in vitro study investigated both health-affecting and potential health-promoting mechanisms of airborne phycotoxin exposure, by analyzing cell viability effects via cytotoxicity assays and effects on the mTOR pathway via western blotting. To that end, A549 and BEAS-2B lung cells were exposed to increasing concentrations (ng·L−1–mg·L−1) of (1) pure phycotoxins and (2) an extract of experimental aerosolized homoyessotoxin (hYTX). The lowest cell viability effect concentrations were found for the examined yessotoxins (YTXs). Contradictory to the other phycotoxins, these YTXs only induced a partial cell viability decrease at the highest test concentrations. Growth inhibition and apoptosis, both linked to mTOR pathway activity, may explain these effects, as both YTXs were shown to downregulate this pathway. This proof-of-principle study supports the biogenics hypothesis, as specific aerosolizable marine products (e.g., YTXs) can downregulate the mTOR pathway.

Lysosomes, Autophagy, and Hormesis in Cell Physiology, Pathology, and Age-Related Disease

“…Growth inhibition and apoptosis, both linked to mTOR pathway activity, may explain these effects, as yessotoxins were shown to downregulate this pathway. 102 Fungal toxins, such as aflatoxins and ochratoxins, can also induce autophagy and apoptosis and interact via cell signaling pathways; and there appears to be some evidence for hormetic effects. 103 Evidently, hormesis and phytohormesis resulting from exposure to small amounts of toxic pollutants or some naturally occurring biogenic chemicals (ie, from both prokaryotes and eukaryotes) can have a stimulatory effect on the various cellular or cytoprotective processes including autophagy (Table 1).…”

“…Growth inhibition and apoptosis, both linked to mTOR pathway activity, may explain these effects, as yessotoxins were shown to downregulate this pathway. 102 Fungal toxins, such as aflatoxins and ochratoxins, can also induce autophagy and apoptosis and interact via cell signaling pathways; and there appears to be some evidence for hormetic effects. 103…”

The Effects of Air Pollution, Sea Exposure and Altitude on COVID-19 Hospitalization Rates in Italy

“…Medical literature shows that living near the coast can increase health and wellbeing [ 17 , 18 , 19 , 20 ]. A recent study carried out by the University of Gand (Belgium) and the Flamine Marine Institute (VLIZ) has found that seawater contains microbiota and biogenic molecules which could affect human health [ 21 ]. It has also been shown that living in coastal areas improves vitamin D concentration helping to reduce cardiovascular diseases [ 22 , 23 , 24 , 25 ].…”

Phycotoxin-Enriched Sea Spray Aerosols: Methods, Mechanisms, and Human Exposure

“…95,96 Sea sprayaerosolized OA, investigated here for the first time, is unlikely to pose a risk to human health. We conclude this because (1) the respiratory system is not expected to be more sensitive than the digestive system based on OA's mode of action 97 and in vitro experiments using lung 33,98 and intestinal cells 99 and (2) the European regulatory limit for OA in commercial bivalves 100 (160 μg OA kg −1 , i.e., maximum digestive intake) is over 10 4 times higher than the dose one could inhale during a 48 h period. This maximum 48 h exposure equals to 14 ng of OA and assumes an extremely high inhalation flow rate (100 L min −1 ) 101 of the highest [OA] coastal air determined here (i.e., 51 pg m −3 ).…”

“…Conversely, no human intoxication has ever been reported for yessotoxins (YTXs) . Recent research into the bioactivity of YTXs even points to their potential therapeutic use. − YTXs have been shown to downregulate the mammalian target of rapamycin (mTOR) pathway. ,, The downregulation of this cell signaling pathway is crucial in Moore’s biogenics hypothesis as it has been associated with longevity, anticancer properties, and other beneficial health effects, while an increased activity is related to multiple pathological conditions (e.g., cancers, type 2 diabetes, and neurodegenerative diseases) . Indeed, Moore hypothesized that regular airborne exposure to aerosolized natural compounds causes health-promoting effects via downregulation of the mTOR pathway.…”