Mass spectrometry-based lipidomics to explore the naphthalene toxicity in a tolerant mouse model
Date Issued
2014
Date
2014
Author(s)
Hong, Si-Han
Abstract
Naphthalene, a slightly water soluble volatile aromatic hydrocarbon,
is present in both groundwater and air emissions from a variety of sources. Naphthalene is a site- and species- selective cytotoxicant. The cell injury is found in mouse distal airways where the nonciliated or Clara cell is particularly susceptible to naphthalene toxicity. Naphthalene induced airway injury is related to lipid peroxidation, disruptions of membrane components, and imbalanced energy supply based on NMR-based metabolomics studies.
Previously, our lab has investigated the mechanisms of naphthalene toxicity in various mouse tissues among injured, tolerant, and the control mice using 1H NMR-based metabolomics. Male ICR mice were administered seven repeated injections (ip) of naphthalene (0, 200 mg/kg/day) in olive oil and gave a challenge dose (300 mg/kg/day) at the eighth day. From the metabolomic results, the single exposure effects of naphthalene on the respiratory system are associated with cellular membrane damages and energy metabolism disturbance. However, the repeated exposure induced the antioxidation mechanism associated with glutathione in the airway; therefore, mice become tolerant to naphthalene toxicity. Furthermore, there is no airway injury in this model.
Glycerophospholipids are key components of biological membranes. They also have a variety of biological functions, such as cellular messengers, enzyme activators and etc. In this study, we especially focus on the most abundant phosphorylcholine-containing lipids, including phosphatidylcholine (PC) and sphingomyelin (SM) and associate the changes of them with protective effects in a naphthalene tolerant mouse model. Moreover, critical toxic mechanisms of naphthalene will be revealed in this study.
In this study, we intend to understand the mechanism of naphthalene-induced cell injury or tolerance by profiling changes of phosphorylcholine-containing lipids including PCs and SM by using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) following multivariate statistical analysis. Phosphorylcholine-containing lipid profiling from naphthalene tolerant mice and injury mice will be compared and related with naphthalene toxicity..
From the results of the histopathology, we can easily recognize the single naphthalene dose group had vacuolated and swollen Clara cell in the airways. The lung of the repeated naphthalene dose group appeared to be similar as that in the control which administered with the vehicle (olive oil). Partial least-square-discriminate analysis (PLS-DA) model shows differences between the phosphorylcholine-containing lipid profiling from the analysis of the lung, liver, and kidney from the mice received single dose or the repeated dose of naphthalene. Diacyl PCs, PC with polyunsaturated fatty acyl (PUFA) chains and plasmenylcholine are elevated in the repeated dose group than those in the single dose group, which may be associated with the tolerant phenomenon. Our goal attempts to reveal the mechanisms of tolerance in a naphthalene tolerant mouse model and further understand naphthalene toxicity.
Subjects
甘油磷酸膽鹼
萘
肺部毒性
耐受性
脂質體學
Type
thesis
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