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

Abstract

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 1, 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 timedependent exposure resulting in acute lung injury, which later reaches the vascular system.

The Protective Effects of Shengmai Formula Against Myocardial Injury Induced by Ultrafine Particulate Matter Exposure and Myocardial Ischemia are Mediated by the PI3K/AKT/p38 MAPK/Nrf2 Pathway

“…Similar increases in the levels of HO-1 and NOX in the lung and heart have been reported after particle exposure in rats; the differences were dependent on particulate size ( Aztatzi-Aguilar et al, 2015 ). However, contrary to our findings, a recent study by OG Aztatzi-Aguilar reported a significant increase in SOD2 mRNA expression in the aorta of rats exposed to PM when compared to those in the filtered air group ( Aztatzi-Aguilar et al, 2018 ). One explanation for this discrepancy is that the mRNA expression of SOD2 might have been elevated at the beginning of PM exposure in the previous study to increase the anti-oxidation ability of the myocardial cells and resist free radical damage.…”

Identification of Toxicity Parameters Associated with Combustion Produced Soot Surface Chemistry and Particle Structure by in Vitro Assays

“…Catalase (CAT) serves as a protective enzyme that breaks down H 2 O 2 and eliminates ROS formation. Some studies have shown that exposure to PM 2.5 induces a loss of SOD2 and CAT activity, leading to an accumulation of ROS [24]. PM 2.5 has also been observed to downregulate protein kinase B (Akt) signaling, which is a known modulator of SOD2 and NFE2L2, decreasing the expression of SOD2 and NFE2L2 [49,50].…”

“…Many of the adverse health effects of PM 2.5 exposure are hypothesized to be derived from oxidative stress, which is initiated by the formation of reactive oxygen species (ROS) within cells [24]. Although several studies have demonstrated the ROS potential and inflammatory action of diesel particulates from diesel engine combustion, the causative factors are less clear.…”

Identification of Toxicity Parameters Associated with Combustion Produced Soot Surface Chemistry and Particle Structure by in Vitro Assays

“…Protein carbonylation has also been reported as a biomarker of oxidative stress-induced protein damage and has been associated with the development of cardiovascular and respiratory diseases [22,23]. A few studies have shown that protein carbonylation is increased in PM2.5-treated human keratinocytes and rat epithelial lung cells [24,25]. Thus, while cytokine expression and protein carbonylation may serve as important biomarkers for numerous lung diseases, their role in PM2.5-induced lung inflammation has not been extensively investigated in human cells.…”

“…Many of the adverse health effects of PM2.5 exposure are hypothesized to be derived from oxidative stress, initiated by the formation of reactive oxygen species (ROS) within cells [25]. Though several studies have demonstrated the ROS potential and inflammatory action of diesel particulates from diesel engine combustion, the causative factors are less clear.…”