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Mechanisms of chemically induced respiratory toxicities
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
Chemicals that have been reported to cause Clara cell damage include those categorized under the following classes of compounds: aromatic hydrocarbons (bromobenzene,75 2-methylnaphthalene,76 naphthalene3 and 1-nitronaphthalene77), chlorinated hydrocarbons (bromotrichloromethane,78 carbon tetrachloride,79 1,1-dichloroethylene4 and trichloroethylene5) and furans (4-ipomeanol80 and 3-methylfuran81). Although by no means complete, the chemicals shown underscore the multiplicity and diversity of compounds with the capability of eliciting Clara cell necrosis. All the compounds mediate their lung toxicities through a mechanism involving metabolic activation. The isozyme-selective metabolism of these compounds by cytochrome P450 enzymes has been identified for 4-ipomeanol (CYP4B1, CYP2B4),51,52 3-methylindole (CYP2F),47 naphthalene (CYP2F),3 1,1-dichloroethylene (CYP2E1, CYP2F)48 and trichloroethylene (CYP2E1, CYP2F, 2B1).5 However, it should be emphasized that changes may occur as additional P450 enzymes and their substrates are characterized. All the P450 enzymes implicated in the metabolism of the chemicals are localized in the Clara cells, consistent with the contention that xenobiotic metabolism takes place to the greatest extent in this cell type.
2-Naphthalenemethanol participates in metabolic activation of 2-methylnaphthalene
Published in Xenobiotica, 2022
Kunna Li, Ying Zou, Yang Wang, Mengyue Zhou, Jing Li, Rong Tan, Shiyu Zhang, Weiwei Li, Jiang Zheng
Polycyclic aromatic hydrocarbons (PAHs) and their alkylated derivatives such as methyl naphthalene are ubiquitous environmental pollutants (Boström et al. 2002; Li et al. 2014) and may have mutagenic, teratogenic, and carcinogenic effects (Yao et al. 2017). Naphthalene, 1-methylnaphthalene (1-MN), and 2-methylnaphthalene (2-MN) are the most abundant PAHs congeners in polluted air, such as urban, roadside, and airport (Iavicoli et al. 2006; Li et al. 2010; Masih et al. 2010), where concentrations far exceed those of the less volatile PAHs. An inhalation study revealed that a single dose of 2-MN produced a strong irritant effect in mice and a neurotoxic effect in rats (Korsak et al. 1998). A good correlation between 2-MN dose and lung damage has been observed in mice (Swiercz et al. 2010). Research showed that 2-MN also displayed carcinogenic effects on human squamous epithelial cells (Mueller et al. 2021). 2-MN can be metabolised to 2-naphthalenemethanol (2-NM) by lung microsomes and liver microsomes, and the metabolite can reportedly induce pulmonary toxicity, due to the covalent binding to alveolar protein (Griffin et al. 1983). 2-NM is also one of volatile oil components of Litsea lancilimba Merr, an herbal medicine used in China, particularly in Guizhou Province (Zhao et al. 2009; Zhang et al. 2011). The safety of the herbal medicine has never been evaluated.