DESIGN OF A NEW IN VIVO EXPOSURE DEVICE FOR THE STUDY OF OXIDATIVE STRESS AND CARDIOTOXIC EFFECTS INDUCED BY SUBCHRONIC AND CHRONIC INHALATION OF SIZE-SELECTED PARTICLES OF SEVERAL POLLUTANTS IN YOUNG AND OLD RATS

Environmental sources such as diesel exhausts or wood burning are mainly responsible of the high particulate matter (PM) levels in the urban atmosphere and/or indoor [1,2]. Human exposure to PM pollution is associated with increased respiratory and cardiovascular diseases [3], inhaled ultrafine particles (< 0.1 mM size) being the most harmful component due to their ability to deeply penetrate into lung tissue, to enter blood stream and to reach the heart [3,4]. Since in most animal studies of PM toxicity evaluation, the particles were perfused or instilled, we developed an exposition chamber where stable size- and concentration-controlled particle aerosols (Table 1) can be continuously released for 1−3 hours. Aerosols were prepared from atmospheric-relevant pollutants and chronically and noninvasively delivered (daily for 3−6 months) to rats by inhalation under non-stress conditions. Following the exposure period, rat hearts were Langendorff perfused and their post-ischemic vulnerability was assessed together with other histopathologic, inflammatory and standard indices of oxidative (lipid and DNA oxidation, protein carbonyls) and nitrosative stress in fluids and organs. The data evidenced a strong time-related cardiotoxicity, atherosclerosis and oxidative stress development associated with experimentally-controlled exposure to particles concentrations which could be commonly found in real-life both indoor and outdoor air.