1H NMR-based Metabolomics to Study Effects of Naphthalene on Mouse Tissues
Date Issued
2012
Date
2012
Author(s)
Chung, Meng-Hsuan
Abstract
Naphthalene, a primary polycyclic aromatic hydrocarbon (PAH), widely spread in the environment was hypothesized to relate with adverse health effects. In order to clarify the underlying mechanisms of naphthalene-induce toxicity, extensive studies are required. Therefore, this study intended to investigate the mechanisms of naphthalene-induce toxicity in various tissues of mice. We used high through-put 1H NMR-based metabolomics to study effects of naphthalene on mouse tissues. Dose-response experiments (0, 100 and 200 mg/kg naphthalene, ip) were carried out on male ICR mice. Both hydrophilic and hydrophobic metabolites from the lung, liver and kidney tissues were extracted and analyzed by 1H and p-J-resolved NMR followed by principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA). From our results, the metabolic effects of naphthalene on lung, liver, and kidney demonstrated dose-dependent effects. Our results suggest that naphthalene-induced lung injures were associated with cellular membrane damages and turbulence of energy metabolisms, where declination of glycerophosphocholine and increase of succinate was found in the lung. In the liver, glutamine and UDP-glucose were increased in the 200 mg/kg exposure group. Besides, detoxification nucleophile glutathione, also demonstrated to be increased depending on naphthalene dose in the kidney. Through this study, not only the metabolome of target organ lung but metabolome of liver and kidney were found to respond to naphthalene intervention. The changes of these metabolites may partially explain the pathological response of naphthalene exposure. In conclusion, 1H NMR-based metabolomics is a useful tool in understanding the mechanism of xenobiotic induced toxicities.
Subjects
naphthalene
mouse
lung toxicity
liver
kidney
NMR
metabolomics
Type
thesis
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