Metabolic Effects of Sub-chronic Ambient Particulate Matter Inhalation Exposure in Sprague-Dawley Rats

• Main Authors: Karen T. Cheng, 鄭廷芳
• Other Authors: Tsun-Jen Cheng
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/75134442847004328855

碩士 === 國立臺灣大學 === 職業醫學與工業衛生研究所 === 101 === Both epidemiological and animal studies had indicated clear association between adverse health effects of the pulmonary and cardiovascular system with particulate matter (PM) air pollution. These studies approached the outcomes specifically, suggesting exposure of PM lead to elevation of cytokines and tissue lesions. The use of NMR-based metabolomics provided a global profiling of the endogenous metabolites in our body, aiming at the verification of known biomarkers, clarification of possible toxicological mechanisms, and finding of novel markers. A 12-week whole body ambient PM inhalation exposure design was conducted with 16 male SD rats randomly divided into the ambient air exposure group and the filtered-air group for a 24 hr/day, 7 days/week exposure. Serial sampling of serum was held for adjustment of individual variation at time points of -2 days(baseline), 7 days, 4 weeks, and 12 weeks of exposure for NMR-based metabolomic analysis. Another 16 male SD rats in the same age were also randomly divided into the two groups and were sacrificed for hematological analysis, cell differential and inflammatory biomarker analysis of bronchial alveolar lavage fluid (BALF) at time points of 5 days, 7 days, 4 weeks, and 12 weeks of exposure (N=3/group/time-points). Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and Student’s t-test were employed to identifying critical metabolites for the clarification of possible mechanisms of toxicological effects of PM in the body. The estimated average mass concentration of PM2.5 at 7 days, 4 weeks, and 12 weeks were 20.86μg/m3, 20.87μg/m3, 19.30μg/m3, 13.73μg/m3, respectively. PCA scores plot from the analysis of NMR spectra of serum showed a trend separation and clustering according to exposure and control groups at both 4 and 12 weeks of exposure. Compared to the control group, decrease levels of the -CH2 of LDL and VLDL and increase level of creatine, citrate and choline were found at 5 days of exposure; saturated and unsaturated fatty acid chains, and increase levels of valine, acetate, methionine, tyrosine and creatine were found at 4 weeks of exposure, while valine, alanine, acetoacetate, pyruvate, glutamine, citrate, methionine, choline, phosphocholine, creatine, glucose and tyrosine were found decreased and increase level of –CH2 of LDL and VLDL, saturated fatty acid chain and formate were found at 12 week of exposure. Our findings suggested that sub-chronic inhalation of PM at ambient level might have an association with the perturbation of TCA cycle, energy metabolism, amino acid and lipid metabolism, and disruption of energy production and the increase of ROS production.