In vivo hydroquinone exposure causes tracheal hyperresponsiveness due to TNF secretion by epithelial cells

Author(s)

Borges Shimada, Ana Lucia ^[1] ; Lino-dos-Santos-Franco, Adriana ^[2] ; Bolonheis, Simone Marques ^[1] ; Nakasato, Andre ^[1] ; Damazo, Amilcar Sabino ^[3] ; Tavares-de-Lima, Wothan ^[2] ; Poliselli Farsky, Sandra Helena ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Lab Expt Toxicol, BR-05508 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, BR-05508 Sao Paulo - Brazil

^[3] Univ Fed Mato Grosso, Fac Med Sci, Dept Basic Sci Hlth, Cuiaba, Mato Grosso - Brazil

• Document type: Journal article
• Source: Toxicology Letters; v. 211, n. 1, p. 10-17, 2012.
• Web of Science Citations: 12

Abstract

Hydroquinone (HQ) is the main oxidative substance in cigarette smoke and a toxic product of benzene biotransformation. Although the respiratory tract is an inlet pathway of HQ exposure, its effect on airway muscle responsiveness has not been assessed. We thus investigated the effects of low dose in vivo HQ-exposure on tracheal responsiveness to a muscarinic receptor agonist. Male Swiss mice were exposed to aerosolised 5% ethanol/saline solution (HQ vehicle; control) or 0.04 ppm HQ (1 h/day for 5 days) and tracheal rings were collected 1 h after the last exposure. HQ exposure caused tracheal hyper-responsiveness to methacholine (MCh), which was abolished by mechanical removal of the epithelium. This hyperresponsiveness was not dependent on neutrophil infiltration, but on tumour necrosis factor (TNF) secretion by epithelial cells. This conclusion was based on the following data: (1) trachea from HQ-exposed mice presented a higher amount of TNF, which was abrogated following removal of the epithelium; (2) the trachea hyperresponsiveness and TNF levels were attenuated by in vivo chlorpromazine (CPZ) treatment, an inhibitor of TNF synthesis. The involvement of HQ-induced TNF secretion in trachea mast cell degranulation was also demonstrated by the partial reversion of tracheal hyperresponsiveness in sodium cromoglicate-treated animals, and the in vivo HQ-exposure-induced degranulation of trachea connective tissue and mucosal mast cells, which was reversed by CPZ treatment. Our data show that in vivo HQ exposure indirectly exacerbates the parasympathetic-induced contraction of airway smooth muscle cells, mediated by TNF secreted by tracheal epithelial cells, clearly showing the link between environmental HQ exposure and the reactivity of airways. (C) 2012 Elsevier Ireland Ltd. All rights reserved. (AU)

• FAPESP's process: 09/03964-5 - Characterization of mechanisms of action of in vivo hydroquinone exposure on lung mast cells and macrophages
• Grantee: Ana Lucia Borges Shimada
• Support Opportunities: Scholarships in Brazil - Master