Abstract
Naphthalene, the most common polycyclic aromatic hydrocarbon, causes airway epithelium injury in mice. Repeated exposure of mice to naphthalene induces airway epithelia that are resistant to further injury. Previous studies revealed that alterations in bioactivation enzymes and increased levels of gamma-glutamylcysteine synthase in the bronchioles protect tolerant mice from naphthalene and its reactive metabolites. In our current study, tolerance was induced in male ICR mice using a total of 7 daily intraperitoneal injections of naphthalene (200 mg/kg). Both naphthalene-tolerant and non-tolerant mice were challenged with a dose of 300 mg/kg naphthalene on day 8 to investigate metabolite differences. The lungs, liver, and kidneys were collected for histopathology 24 h after the challenge dose. Bronchial alveolar lavage fluid (BALF) and both hydrophilic and hydrophobic extracts from each organ were analyzed using nuclear magnetic resonance (NMR)-based metabolomics. The histological results showed no observable injuries to the airway epithelium of naphthalene-tolerant mice when compared with the control. In contrast, airway injuries were observed in mice given a single challenge dose (injury mice). The metabolomics analysis revealed that the energy metabolism in the lungs of tolerant and injury mice was significantly perturbed. However, antioxidant metabolites, such as glutathione and succinate, were significantly increased in the lungs of tolerant mice, suggesting a role for these compounds in the protection of organs from naphthalene-induced electrophilic metabolites and free radicals. Damage to the airway cellular membrane, as shown by histopathological results and increased acetone in the BALF and perturbation of hydrophobic lung extracts, including cholesterol, phosphorylcholine-containing lipids, and fatty acyl chains, were observed in injury mice. Consistent with our histopathological results, fewer metabolic effects were observed in the liver and kidney of mice after naphthalene treatments. In conclusion, NMR-based metabolomics reveals possible mechanisms of naphthalene tolerance and naphthalene-induced toxicity in the respiratory system of mice.
Highlights
Naphthalene is the most common polycyclic aromatic hydrocarbon and is found in the environment
Selected mice were divided into three groups (n = 6 per group): (1) a control group that received an intraperitoneal administration of vehicle; (2) a single-dose treatment group that received an intraperitoneal administration of vehicle; and (3) a repeated treatment group that received an intraperitoneal administration of 200 mg/kg naphthalene
Vacuolization in ciliated bronchiolar (Clara) cells was observed in the injury mice (S1C Fig)
Summary
Naphthalene is the most common polycyclic aromatic hydrocarbon and is found in the environment. Large numbers of industrial plants and automobiles consume fuels that produce incomplete combustions that release significant amounts of naphthalene into the environment. The wide application of naphthalene in insecticides and surfactants has led to its accumulation in the environment. Humans are most likely to be exposed to naphthalene by inhaling naphthalene vapors. The second major route of exposure is dietary and non-dietary ingestion due to the use of naphthalene in insecticides. Workers in certain occupations, such as firefighters and naphthalene-related industrial workers are exposed to naphthalene at high levels [1,2,3]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
