Research Article: Mass spectrometry-based lipidomics to explore the biochemical effects of naphthalene toxicity or tolerance in a mouse model

Date Published: October 1, 2018

Publisher: Public Library of Science

Author(s): Sheng-Han Lee, Si-Han Hong, Chuan-Ho Tang, Yee Soon Ling, Ke-Han Chen, Hao-Jan Liang, Ching-Yu Lin, Anna Halama.


Naphthalene causes mouse airway epithelial injury. However, repeated exposures of naphthalene result in mouse airway tolerance. Previous results showed that toxicity or tolerance was correlated with changes of phosphorylcholine-containing lipids. In this study, a mass spectrometry-based lipidomic approach was applied to examine the effects of naphthalene-induced injury or tolerance in the male ICR mice. The injury model was vehicle x 7 plus 300 mg/kg naphthalene while the tolerant one was 200 mg/kg daily x 7 followed by 300 mg/kg naphthalene on day 8. The lung, liver, kidney, and serum samples were collected for profiles of phosphorylcholine-containing lipids including phosphatidylcholines (PCs) and sphingomyelins (SMs). A partial least-square-discriminate analysis model showed different lung phosphorylcholine-containing lipid profiles from the injured, tolerant, and control groups. Perturbation of diacyl-PCs and plasmenylcholines may be associated with enhanced membrane flexibility and anti-oxidative mechanisms in the lungs of tolerant mice. Additionally, alterations of lyso-PCs and SMs may be responsible for pulmonary dysfunction and inflammation in the lungs of injured mice. Moreover, serum PC(16:0/18:1) has potential to reflect naphthalene-induced airway injuries. Few phosphorylcholine-containing lipid alterations were found in the mouse livers and kidneys across different treatments. This study revealed the changes in lipid profiles associated with the perturbations caused by naphthalene tolerance and toxicity; examination of lipids in serum may assist biomarker development with the potential for application in the human population.

Partial Text

Naphthalene, the most common polycyclic aromatic hydrocarbon (PAH), is present in both air and groundwater from a variety of sources, such as industrial plants, vehicle traffic, and forest fires [1, 2]. In addition, moth repellents, cigarette smoking, deodorant and furniture also release certain amounts of naphthalene [3]. Studies have shown that naphthalene can be detected in various tissues and organs from farm animals and human bodies [4–7].

In this study, we utilized MS-based lipidomics to explore respiratory toxicity induced by naphthalene by examining lipid alterations between an injury model and tolerant model. Effects on non-susceptible organs (liver and kidney) were also examined. The final goal was to associate changes of lipid profiles with toxic or protective effects of naphthalene-induced injury or tolerance.

Naphthalene-induced respiratory toxicity or tolerance was correlated with changes in phosphorylcholine-containing lipids were suggested by our previous 1H NMR-based metabolomic approach. In this study, we examined alternations of phosphorylcholine-containing lipids in the lung, liver, kidneys, and serum by UPLC-MS/MS in order to understand naphthalene toxicity or tolerance in target, non-target organs, and biofluids. Fewer phosphorylcholine-containing lipid effects of naphthalene treatments were found in the liver and kidneys compared to the lung. Higher ratios of phosphorylcholine-containing lipids were altered in the lungs of naphthalene treated mice than those in other organs, demonstrating that the lung is more susceptible to naphthalene. Naphthalene-induced respiratory toxicity or tolerance is correlated with lipid perturbation. In the lungs of tolerant mice, strengthened membrane flexibility by increases of diacyl-PCs and consumption of anti-oxidative relating lipids, such as P-PCs, were observed against naphthalene-induced molecular perturbation. On the other hand, the alteration of lyso-PCs and SMs could reflect perturbed cell function and pulmonary inflammation in the lungs of injured mice. The alteration of phosphorylcholine-containing lipid fingerprints in the mouse lungs of our tolerant model (7 day period) illustrated several protective roles to against naphthalene insults in this study. However, the effects of chronic naphthalene exposure have shown the carcinogenic potentials in animal models. More studies are warranted to provide more evidences for investing the variety of naphthalene-mediated responses. Further examination of the critical lipids related to pulmonary injury in serum will help us to understand the information on pulmonary toxicity for application in the human population.




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