SESSION TYPE: Cytokines/Cellular Interactions Posters
PRESENTED ON: Wednesday, October 24, 2012 at 01:30 PM - 02:30 PM
PURPOSE: Cigarette Smoke is a potent inducer of oxidative stress and one of the causes of COPD (Chronic obstructive pulmonary disease). The glutathione (GSH) system has a key role in redox regulatory mechanisms and we already demonstrated that the mucoactive drug S-Carbomethylcysteine Lysine salt (S-CMC-Lys) is able to significantly increase GSH secretion in human respiratory cells and reduce Reactive Oxigen Species (ROS) production following the exposure to H2O2. In this study we evaluated S-CMC-Lys effects on GSH intracellular content and metabolism after an oxidative stress induced by CSE (Cigarette Smoke Extract).
METHODS: GSH and ROS levels were evaluated with fluorimetric assays in the respiratory cell lines 16HBE14o- and WI-26VA4. The expression of GSH related enzymes was detected by real-time PCR. S-CMC-Lys (100 µM) induced in both cell lines a significant increase of intracellular GSH and a significant increase in the expression of the catalytic subunit of γ-GCS (γ-Glutamyl Cysteine Synthase), a key enzyme for the synthesis of GSH. The effect of CSE exposure was assessed on the respiratory 16HBE14o- cell line and characterized in terms of cell toxicity and action on intracellular GSH.
RESULTS: S-CMC-Lys pre-treatment prior to 5% CSE exposure reduced ROS, without affecting the GSH intracellular concentration. At lower CSE concentrations (2.5%) the pre-treatment with S-CMC-Lys, followed by co-treatment with CSE, was able to significantly reduce the GSH dropdown induced by CSE. Co-subministration of S-CMC-Lys with 5% CSE for a prolonged period (24 hours) resulted in an increase in the GSH concentration and significantly increased levels of γ-GCS and GR (glutathione reductase) mRNA, when compared to the sole CSE exposure. S-CMC-Lys increases the intracellular GSH in respiratory cells, possibly by enhancing the expression of γ-GCS catalytic subunit. The pre-treatment of respiratory cells with S-CMC-Lys may exert a protective function during oxidative stress, thus reducing the ROS-mediated inflammatory response.
CONCLUSIONS: The subministration of S-CMC-Lys may be of help in counteracting COPD and CSE negative effects on the GSH system and ROS production, by potentiating the adaptive response of respiratory cells to CSE.
CLINICAL IMPLICATIONS: The subministration of S-CMC-Lys, by potentiating the adaptive response of respiratory cells to CSE, may be of help in counteracting chronic obstructive pulmonary disease and CSE negative effects on the GSH system and ROS production.
DISCLOSURE: The following authors have nothing to disclose: Claudia Bazzini, Rossella Balsamo, Luigi Lanata, Francesca Sassone, Valeria Rossetti, Giuliano Meyer
No Product/Research Disclosure InformationDompe SPA, Milan, Italy