Rat lung response to ozone and fine particulate matter (PM_2.5) exposures

Abstract

Exposure to different ambient pollutants maybe more toxic to lung than exposure to a single pollutant. In this study, we discussed the inflammation and oxidative stress responses of rat lung caused by ozone and PM2.5 versus that of rats exposed to saline, ozone, or single PM2.5 . Wistar rats inhaled 0.8 ppm ozone or air for 4 h and then placed in air for 3 h following intratracheal instillation with 0, 0.2 (low dose), 0.8 (medium dose), 3.2 (high dose) mg/rat PM2.5 dissolved in sterile saline (0.25 mL/rat), repeated twice per week for 3 weeks, the cumulative doses of PM2.5 in animals were 1.2, 4.8, and 19.2 mg. Rats were sacrificed 24 h after the last (sixth) exposure. The collected bronchoalveolar lavage fluid (BALF) was analyzed for inflammatory cells and cytokines. Lung tissues were processed for light microscopic and transmission electron microscopic (TEM) examinations. Results showed that total cell number in BALF of PM2.5 -exposed groups were higher than control (p < 0.05). PM2.5 instillation caused dose-trend increase in tumor necrosis factor alpha (TNF-α), interleukin-6, lactate dehydrogenase, and total protein of BALF. Exposure to ozone alone only caused TNF-α significant change in above-mentioned indicators of lung injury. On the other hand, ozone could enhance PM2.5-induced inflammatory changes and pathological characters in rat lungs. SOD and GSH-Px activities in lung were reduced in PM2.5-exposed rats with and without prior ozone exposure compared to control. To determine whether the PM2.5 and ozone affect endothelium system, iNOS, eNOS, and ICAM-1 mRNA levels in lung were analyzed by real-time PCR. These data demonstrated that inflammation and oxidative stress were involved in toxicology mechanisms of PM2.5 in rat lung and ozone potentiated these effects induced by PM2.5. These results have implications for understanding the pulmonary effects induced by ozone and PM2.5.

PM2.5-Induced Oxidative Stress and Mitochondrial Damage in the Nasal Mucosa of Rats

“…The total PM 2.5 exposure levels in this study therefore corresponded with previous intratracheal instillation studies, which defined a low dose as 0.2 mg/rat, a medium dose as 0.8 mg/rat, and a high dose as 3.2 mg/rat [14]. The levels of PM 2.5 exposure in our study were 8-(LPM 2.5 ), 40-(MPM 2.5 ), and 120-(HPM 2.5 ) fold higher than air quality guidance by the World Health Organization (WHO) (PM 2.5 , 25 μg/m 3 over a 24 h period).…”

Metabolomics analysis reveals that benzo[a]pyrene, a component of PM2.5, promotes pulmonary injury by modifying lipid metabolism in a phospholipase A2-dependent manner in vivo and in vitro

“…PM 2.5 has been reported to induce the production of reactive oxygen species in neutrophils of asthmatic patients, which is involved in neutrophil activation and pulmonary injury [28]. The expression of adhesion molecules in endothelium is also up regulated after treatment of PM 2.5 [29], [30], facilitating the migration of neutrophils into the lung.…”

Insights in particulate matter‐induced allergic airway inflammation: Focus on the epithelium

“…As pretreatment with antioxidants can affect intracellular signalling pathways and decrease cytokine production, enhancing the levels of the antioxidant superoxide dismutase (SOD) or influencing the glutathione (GSH) system, for instance, could be another approach to lower oxidative stress and airway inflammation . Especially since both asthma and PM exposure have already been associated with a significant reduction in SOD or polymorphisms in genes implicated in the GSH system have been detected . Moreover, also dietary antioxidants, such as selenium, were already associated with reduced oxidative stress and lung inflammation in a model of PM‐induced lung injury .…”

“…[207][208][209][210] Especially since both asthma and PM exposure have already been associated with a significant reduction in SOD or polymorphisms in genes implicated in the GSH system have been detected. 104,106,[211][212][213] Moreover, also dietary antioxidants, 209,214 such as selenium, were already associated with reduced oxidative stress and lung inflammation in a model of PM-induced lung injury. 177…”