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Oxidative Medicine and Cellular Longevity
Volume 2015 (2015), Article ID 787561, 15 pages
Research Article

Pituitary Adenylate Cyclase-Activating Polypeptide Reverses Ammonium Metavanadate-Induced Airway Hyperresponsiveness in Rats

1Laboratory of Integrated Physiology, Science Faculty of Bizerte, Carthage University, 7021 Zarzouna, Tunisia
2National Institute of Health and Medical Research (INSERM), U982, 76821 Mont-Saint-Aignan Cedex, France
3Institute for Research and Innovation in Biomedicine (IRIB), Normandy University, 76821 Mont-Saint-Aignan Cedex, France
4Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen University, 76821 Mont-Saint-Aignan Cedex, France
5Laboratory of Physiology and Functional Exploration, CHU Farhat Hached, 4000 Sousse, Tunisia
6Laboratory of Pathologic Anatomy, CHU Farhat Hached, 4000 Sousse, Tunisia

Received 8 December 2014; Revised 15 May 2015; Accepted 18 May 2015

Academic Editor: Vladimir Jakovljevic

Copyright © 2015 Mounira Tlili et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The rate of atmospheric vanadium is constantly increasing due to fossil fuel combustion. This environmental pollution favours vanadium exposure in particular to its vanadate form, causing occupational bronchial asthma and bronchitis. Based on the well admitted bronchodilator properties of the pituitary adenylate cyclase-activating polypeptide (PACAP), we investigated the ability of this neuropeptide to reverse the vanadate-induced airway hyperresponsiveness in rats. Exposure to ammonium metavanadate aerosols (5 mg/m3/h) for 15 minutes induced 4 hours later an array of pathophysiological events, including increase of bronchial resistance and histological alterations, activation of proinflammatory alveolar macrophages, and increased oxidative stress status. Powerfully, PACAP inhalation (0.1 mM) for 10 minutes alleviated many of these deleterious effects as demonstrated by a decrease of bronchial resistance and histological restoration. PACAP reduced the level of expression of mRNA encoding inflammatory chemokines (MIP-1, MIP-2, and KC) and cytokines (IL-1 and TNF-) in alveolar macrophages and improved the antioxidant status. PACAP reverses the vanadate-induced airway hyperresponsiveness not only through its bronchodilator activity but also by counteracting the proinflammatory and prooxidative effects of the metal. Then, the development of stable analogs of PACAP could represent a promising therapeutic alternative for the treatment of inflammatory respiratory disorders.