Residential ventilation and carcinogenesis
نویسنده
چکیده
The adverse effects of the most widely recognized greenhouse gas and pollutant on the planet, carbon dioxide, are also the most ubiquitously overlooked when present as a (processed) food ingredient, as a (supercritical) solvent and as an excipient. CO2 is a constituent of carbonated beverages, used as an insufflation gas and to elevate alveolar CO2 concentration in acute respiratory distress syndrome (ARDS). It is used in endoscopic and dermatological cryotherapy, as a solvent in food, chemical and pharmaceutical supercritical extraction processes, as an inert atmosphere during certain types of active pharmaceutical ingredient (API), excipient and drug product manufacture and in fire extinguishers. Notably, it is also breathed in at ~6 times its concentration in atmospheric air over one third of the lifetime of individuals who dwell in closed mechanically ventilated environments. Increased CO2 concentration (or partial pressure); independent of extracellular pH (1) as well as sensing enzymes associated with the hypoxia inducible factor (HIF) pathway in vitro; correlated with a suppression of genes involved the regulation of innate immunity and inflammation (2). This phenomenon, in turn, was largely attributed to altered activity of the nuclear factor-kappa B (NF-kB) family of transcription factors (3). Elevated CO2 (hypercapnia) inhibited autophagy in the human macrophage independently of acidosis by inducing the expression of antiapoptotic factors Bcl-2 and Bcl-xL (4). Hypercapnia suppressed macrophage synthesis of pro-inflammatory cytokines tumor necrosis factor (TNF) and Interleukin (IL-6), phagocytosis and the generation of reactive oxygen species (ROS) by lung neutrophils (5) independently of intra or extracellular acidosis by mouse and human macrophages in vitro. Epithelial cell lines from mice exposed to CO2 concentrations above 5% resulted in the increased transcription and secretion of proinflammatory cytokines resulting in lung inflammation in vivo (6). Corresponding author Corresponding author: 5204 Coventry Court, Colleyville, TX 76034, Tel: 817 501 2984, e-mail: [email protected]
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تاریخ انتشار 2016