CARDIOPULMONARY TOXICITY STUDY OF AMBIENT PARTICULATE MATTERS
Date Issued
2005
Date
2005
Author(s)
Lei, Yu-Chen
DOI
en-US
Abstract
An increasing amount of epidemiological evidences suggest that the effect of particulate air pollution on the cardiopulmonary system is a significant public health concern. However, the biological plausibility remains unclear. Recently, the cardiopulmonary toxicities of particulate matter (PM) are under active investigation. Studies suggest that specific components of PM are responsible for the related toxicity, such as acidity salts, metals and endotoxin. The characteristics of PM may also be associated with adverse effects, such as particle size, surface area and the surface activity. Recent studies further indicate that the susceptibility of subjects exposed to PM is associated with PM-induced health effects. Epidemiologic studies report that the elderly, children and subjects with pre-existing respiratory and cardiovascular disease are more susceptible to PM. Recent investigations further indicate that diabetics may be another susceptible population in PM-related cardiovascular events. However, the exact biological mechanisms still need to be clarified.
In order to investigate the biological plausibility of PM-induced toxicity, and to provide evidence in public health and pollution control, it is necessary to establish the link between PM exposure and toxicological evidence. The aim of this study is to apply the principles of inhalation toxicology in investigating PM-induced pulmonary and cardiovascular toxicity. We used pulmonary and cardiovascular diseased animal models to examine the acute effects after exposed to fine particles (PM2.5) and ultrafine particles (<100nm).
At fist, we set up ambient particle concentrator and animal inhalation exposure system. Using monocrotaline (MCT)-induced pulmonary hypertensive rats as pulmonary diseased animals, we investigated the acute effects after exposed to PM in a traffic busy area near EPA supersite in Taipei city and to PM during Asian dust events. Our results revealed, significant pulmonary inflammation and injury, and increase in proinflammatory cytokine were observed in MCT-pulmonary hypertensive rats exposed to PM in traffic busy area. We also found a significantly increased pulmonary inflammation and WBC in peripheral blood in MCT-pulmonary hypertensive rats exposed to PM during Asian dust events for only 6 hours. There was a dose-response relationship between this observation and the concentration of Asian dust events. We found the components of PM in traffic busy area and PM during dust storm were not identical. PM in traffic busy area contained higher proportion of sulfate, however, PM during dust storm consisted largely of silica and aluminum. It is not clear whether these different components were responsible for the pulmonary toxicity. This was the first report that PM during dust storm caused pulmonary toxicity on diseased animals. We suggested these effects might be associated with the absorbed pollutants and endotoxin on PM, or be associated with the higher number concentration of smaller particles. Using state of art ambient particle concentrator can reflex the nature of ambient particles, however it has the limitation in differentiating specific particle size. Recent studies indicate that ultrafine fraction of ambient PM may be responsible for the adverse health effects. We used artificial polystyrene particles, including 64, 202 and 535nm, to examine the effect of particle size on pulmonary toxicity. We found after intratracheally instilled with same mass concentration, ultrafine particle (64nm) resulted more significant pulmonary inflammation and injury as compared to larger particles (202 and 535nm) in MCT-pulmonary hypertensive rats. Moreover, exposed to ultrafine particles caused significant oxidative stress, including depletion of glutathione (GSH) in lung tissue, and increase in plasma 8-OHdG. Further analysis revealed that these effects were associated with instilled total particle surface area. We suggested that not only particle size, but the surface area of PM might play important role on PM-induced pulmonary toxicity.
In addition to pulmonary toxicity, PM-induced cardiovascular toxicity becomes concerning issue. However, cardiovascular diseased animals in previous studies have some limitation. We found pathophysiology of diabetes might share the common pathway with PM-induced cardiovascular events, including excess generation of oxidative stress, systemic inflammation and vascular endothelial dysfunction. Therefore, we firstly used strepotozotocin (STZ)-diabetic rat as cardiovascular diseased animal model in PM-related study. To avoid possible confounding factors in the confined space of nose-only exposure chamber, we used the method of intratracheal instillation to investigate the cardiovascular toxicity after treatment with PM2.5 collected in a traffic busy area near Taipei EPA supersite. The results revealed that exposure to caused pulmonary toxicity in both diabetic and healthy rats, and the extent of these effects didn’t be modified by the status of diabetes. Interestingly, we found that increases of 8-OHdG and ET-1 were more prominent in diabetic rats. For 8-OHdG generation, diabetic rats exposed to PM demonstrated a 15.6 % increase; however, non-diabetic rats exposed to PM showed only 4.0 % increase. A 40.3 % increase in plasma ET-1 after PM exposure was observed in diabetic rats, while there was only a 2.6 % increase in plasma ET-1 after PM exposure in non-diabetic rats. General linear model was further used to test the interaction between diabetes and PM. We found there were interactions on 8-OHdG (Table 3.1.4, p<0.01) and ET-1 (p=0.08). We further investigated the effects of ultrafine PM on diabetic rats. We found ultrafine carbon black (14nm) caused significant pulmonary inflammation. Exposed to ultrafine carbon black further resulted in significant increase of systemic inflammation, increase of ET-1 and decrease of NO in diabetic rats.
Our results demonstrated that biological plausibility that fine particles (PM2.5) would cause cardiopulmonary toxicity in compromised diseased animals. We also found ultrafine particles might play important role on PM-induced cardiopulmonary effects. This study provided toxicological supports for previous epidemiologic observations. We further believed that STZ-diabetic rat could be further applied in the mechanistic studies of PM-induced cardiovascular events.
Subjects
空氣懸浮微粒
心肺毒性
cardiopulmonary toxicity
ambient particulate matters
Type
thesis
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