利用核磁共振光譜儀的代謝體學來研究萘對小鼠組織的影響

鍾孟軒

doi:10.6342/NTU.2012.02009

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利用核磁共振光譜儀的代謝體學來研究萘對小鼠組織的影響

1H NMR-based Metabolomics to Study Effects of Naphthalene on Mouse Tissues

鍾孟軒 , Masters　　Advisor：林靖愉　　

繁體中文 DOI： 10.6342/NTU.2012.02009

萘小鼠；肺部疾病；肝；腎；核磁共振光譜儀；代謝體學； naphthalene ； mouse ； lung toxicity ； liver ； kidney ； NMR ； metabolomics

Abstract │ Reference (61) │ Altmetrics

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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.

Reference ( 61 ) 〈TOP〉

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