Influence of dose and exposition time in the effectiveness of N-Acetyl-l-cysteine treatment in A549 human epithelial cells
Paula Montero,
Inés Roger,
Cristina Estornut,
Javier Milara,
Julio Cortijo
Affiliations
Paula Montero
Department of Pharmacology, Faculty of Medicine, University of Valencia, 46010, Valencia, Spain; Faculty of Health Sciences, Universidad Europea de Valencia, 46010, Valencia, Spain; Corresponding author. Department of Pharmacology, Faculty of Medicine, University of Valencia, 46010, Valencia, Spain.
Inés Roger
Department of Pharmacology, Faculty of Medicine, University of Valencia, 46010, Valencia, Spain; Faculty of Health Sciences, Universidad Europea de Valencia, 46010, Valencia, Spain; Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), Health Institute Carlos III, 28029, Madrid, Spain
Cristina Estornut
Faculty of Health Sciences, Universidad Europea de Valencia, 46010, Valencia, Spain
Javier Milara
Department of Pharmacology, Faculty of Medicine, University of Valencia, 46010, Valencia, Spain; Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), Health Institute Carlos III, 28029, Madrid, Spain; Pharmacy Unit, University General Hospital Consortium, 46014, Valencia, Spain
Julio Cortijo
Department of Pharmacology, Faculty of Medicine, University of Valencia, 46010, Valencia, Spain; Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), Health Institute Carlos III, 28029, Madrid, Spain; Research and Teaching Unit, University General Hospital Consortium, 46014, Valencia, Spain
N-Acetyl-l-cysteine (NAC) acts as a precursor of the tripeptide glutathione (GSH), one of the principal cell mechanisms for reactive oxygen species (ROS) detoxification. Chronic obstructive pulmonary disease (COPD) is associated with enhanced inflammatory response and oxidative stress and NAC has been used to suppress various pathogenic processes in this disease. Studies show that the effects of NAC are dose-dependent, and it appears that the efficient doses in vitro are usually higher than the achieved in vivo plasma concentrations. However, to date, the inconsistencies between the in vitro NAC antioxidant and anti-inflammatory in vitro effects, by reproducing the in vivo NAC plasma concentrations as well as high NAC concentrations. To do so, A549 were transfected with polyinosinic-polycytidylic acid (Poly (I:C)) and treated with NAC at different treatment periods. Oxidative stress, release of proinflammatory mediators and NFkB activation were analyzed. Results suggest that NAC at low doses in chronic administration has sustained antioxidant and anti-inflammatory effects, while acute treatment with high dose NAC exerts a strong antioxidant and anti-inflammatory response.
