Exposure to ambient particulate matter induces oxidative stress in lung and aorta in a size- and time-dependent manner in rats

Exposure to particulate matter (PM) has been implicated in oxidative stress (OxS) and inflammation as underlying mechanisms of lung damage and cardiovascular alterations. PM is a chemical mixture that can be subdivided according to their aerodynamic size into coarse (CP), fine (FP), and ultrafine (UFP) particulates. We investigated, in a rat model, the induction of OxS (protein oxidation and antioxidant response), carcinogen-DNA adduct formation, and inflammatory mediators in lung in response to different airborne particulate fractions, CP, FP, and UFP, after an acute and subchronic exposure. In addition, OxS was evaluated in the aorta to assess the effects beyond the lungs. Exposure to CP, FP, and UFP induced time- and size-dependent lung protein oxidation and DNA adduct formation. After acute and subchronic exposure, nuclear factor erythroid-2 (Nrf2) activation was observed in the lung, by electrophoretic mobility shift assay, and the induction of mRNA antioxidant enzymes in the FP and UFP groups, but not in the CP. Cytokine concentration of interleukin 1β, interleukin 6, and macrophage inflammatory protein-2 was significantly increased in bronchoalveolar lavage fluid after acute exposure to FP and UFP. Activation of Nrf2 and expression of mRNA antioxidant enzymes were observed only after the subchronic exposure to FP and UFP in the aorta. Our results indicate that FP and UFP were mainly accountable for the oxidant toxic effects in the lung; OxS is spread from the lung to the cardiovascular system. We conclude that the biological mechanisms associated with transient OxS and inflammation are particle size and time-dependent exposure resulting in acute lung injury, which later reaches the vascular system.