RESUMO
Sulfurous thermal waters (STWs) are used as a complementary treatment for allergic rhinitis. However, there is scant data on the effects of STW on nasal epithelial cells, and in vitro models are warranted. The main aim of this study was to evaluate the dose and time effects of exposure to 3D nasal inserts (MucilAirTM-HF allergic rhinitis model) with STW or isotonic sodium chloride solution (ISCS) aerosols. Transepithelial electrical resistance (TEER) and histology were assessed before and after nebulizations. Chemokine/cytokine levels in the basal supernatants were assessed by enzyme-linked immunosorbent assay. The results showed that more than four daily nebulizations of four or more minutes compromised the normal epithelial integrity. In contrast, 1 or 2 min of STW or ISCS nebulizations had no toxic effect up to 3 days. No statistically significant changes in release of inflammatory chemokines MCP-1/CCL2 > IL-8/CXCL8 > MIP-1α/CCL3, no meaningful release of "alarmins" (IL-1α, IL-33), nor of anti-inflammatory IL-10 cytokine were observed. We have characterized safe time and dose conditions for aerosol nebulizations using a novel in vitro 3D nasal epithelium model of allergic rhinitis patients. This may be a suitable in vitro setup to mimic in vivo treatments of chronic rhinitis with STW upon triggering an inflammatory stimulus in the future.
RESUMO
Natural mineral (thermal) waters have been used for centuries as treatment for various diseases. However, the scientific background of such therapeutic action is mostly empiric and based on knowledge acquired over time. Among the various types of natural mineral waters, sulfurous thermal waters (STWs) are the most common type in the center of Portugal. STWs are characterized by high pH, poor mineralization, and the presence of several ions and salts, such as bicarbonate, sodium, fluoride, silica, and carbonate. Furthermore, these waters are indicated as a good option for the treatment of various illnesses, namely respiratory diseases (e.g., allergic rhinitis, asthma, and chronic obstructive pulmonary disease). From the sulfide species present in these waters, hydrogen sulfide (H2S) stands out due to its abundance. In healthy conditions, H2S-related enzymes (e.g., cystathionine ß-synthase and cystathionine γ-lyase) are expressed in human lungs, where they have mucolytic, antioxidant, anti-inflammatory, and antibacterial roles, thus contributing to airway epithelium homeostasis. These roles occur mainly through S-sulfhydration, a post-translational modification through which H2S is able to change the activity of several targets, such as ion channels, second messengers, proteins, among others. However, in respiratory diseases the metabolism of H2S is altered, which seems to contribute somehow to the respiratory deterioration. Moreover, H2S has been regarded as a good biomarker of airway dysfunction and severity, and can be measured in serum, sputum, and exhaled air. Hence, in this review we will recapitulate the effects of STWs on lung epithelial-immune crosstalk through the action of its main component, H2S.
