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

Tlili M, Rouatbi S, Sriha B, Ben Rhouma K, Sakly M, Vaudry D, Wurtz O, Tebourbi O - Oxid Med Cell Longev (2015)

Bottom Line: 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-1α, MIP-2, and KC) and cytokines (IL-1α and TNF-α) 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Integrated Physiology, Science Faculty of Bizerte, Carthage University, 7021 Zarzouna, Tunisia ; National Institute of Health and Medical Research (INSERM), U982, 76821 Mont-Saint-Aignan Cedex, France ; Institute for Research and Innovation in Biomedicine (IRIB), Normandy University, 76821 Mont-Saint-Aignan Cedex, France ; Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen University, 76821 Mont-Saint-Aignan Cedex, France.

ABSTRACT
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/m(3)/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-1α, MIP-2, and KC) and cytokines (IL-1α and TNF-α) 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.

No MeSH data available.


Related in: MedlinePlus

PACAP aerosols reduce AMV-induced inflammatory infiltration and colliquative necrosis in alveolar and bronchiolar tissues. Histological analysis of paraffin-embedded lungs stained with hematoxylin and eosin from animals exposed to vehicle (a, b), AMV aerosols alone (c, d) or followed by inhalation of PACAP aerosols (e, f). The presence of edema (asterisks), the enlargement of air spaces (En), and mononuclear cell infiltration (arrowheads) as well as the pyknotic nuclei (P) are indicated. Representative photomicrographs showing the structure of the alveolar and bronchiolar tissues at low (100x; a, c, and e) and higher (400x; b, d, and f) magnification (n = 8 for each experimental group). A: alveolus; En: air space enlargement; P: pyknotic nucleus; R: respiratory bronchiole; T: terminal bronchiole; V: pulmonary vessels.
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fig4: PACAP aerosols reduce AMV-induced inflammatory infiltration and colliquative necrosis in alveolar and bronchiolar tissues. Histological analysis of paraffin-embedded lungs stained with hematoxylin and eosin from animals exposed to vehicle (a, b), AMV aerosols alone (c, d) or followed by inhalation of PACAP aerosols (e, f). The presence of edema (asterisks), the enlargement of air spaces (En), and mononuclear cell infiltration (arrowheads) as well as the pyknotic nuclei (P) are indicated. Representative photomicrographs showing the structure of the alveolar and bronchiolar tissues at low (100x; a, c, and e) and higher (400x; b, d, and f) magnification (n = 8 for each experimental group). A: alveolus; En: air space enlargement; P: pyknotic nucleus; R: respiratory bronchiole; T: terminal bronchiole; V: pulmonary vessels.

Mentions: As the AMV-dependent increase of lung resistance and its PACAP-mediated reversal may rely on structural changes of airways, we performed a histological study on lungs of treated rats. As expected lung sections of control rats stained with H&E showed normal bronchial lumen. Mucus was not abundant and smooth muscle (SM) layer had normal thickness (Figures 3(a) and 3(b)). In contrast, bronchial sections from rats exposed to vanadium alone showed various histological changes. AMV exposure induced an important accumulation of mucus leading to an obstructed aspect of bronchi. The obstruction appeared also enhanced by the observed hypertrophy of the smooth muscle layer (Figures 3(c) and 3(d)). These histological observations are further confirmed by morphometric analyses (Table 1) showing that the inhalation of vanadium decreased significantly the bronchial lumen diameter (BLD; 107.48 ± 4.77 versus 528.67 ± 9.19 μm for control animals, p < 0.01) and increased significantly the airway smooth muscle layer thickness (ASMT; 39.52 ± 0.89 μm versus 18.66 ± 0.35 μm for control animals, p < 0.01) compared to vehicle-treated animals. Features of cell desquamation were also detected in AMV-treated rats (Figures 3(c) and 3(d)). Lung sections from rats that received PACAP aerosols following vanadium inhalation exhibited a less obstructed bronchial lumen with reduced mucus accumulation (Figures 3(e) and 3(f)). Moreover, the BLD and the airway smooth muscle layer thickness (ASMT) values were significantly decreased compared to vanadium-treated group and were comparable to those of the control group (479.09 ± 24.82 and 16.76 ± 0.41 versus 528.67 ± 9.19 and 18.66 ± 0.35 μm, resp.; Table 1). Likewise, acute AMV exposure led to striking changes in alveolar tissue illustrated by the presence of edema, enlargement of air spaces, mononuclear cell infiltration, and colliquative necrosis characterized by numerous pyknotic nuclei (P) specifically in AMV-treated rats compared to control animals (Figures 4(a) and 4(d)). These AMV-associated histological alterations appeared strongly reduced in PACAP-treated animals (Figures 4(e) and 4(f)), suggesting a PACAP-counteracting action against the AMV-induced toxicity.


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

Tlili M, Rouatbi S, Sriha B, Ben Rhouma K, Sakly M, Vaudry D, Wurtz O, Tebourbi O - Oxid Med Cell Longev (2015)

PACAP aerosols reduce AMV-induced inflammatory infiltration and colliquative necrosis in alveolar and bronchiolar tissues. Histological analysis of paraffin-embedded lungs stained with hematoxylin and eosin from animals exposed to vehicle (a, b), AMV aerosols alone (c, d) or followed by inhalation of PACAP aerosols (e, f). The presence of edema (asterisks), the enlargement of air spaces (En), and mononuclear cell infiltration (arrowheads) as well as the pyknotic nuclei (P) are indicated. Representative photomicrographs showing the structure of the alveolar and bronchiolar tissues at low (100x; a, c, and e) and higher (400x; b, d, and f) magnification (n = 8 for each experimental group). A: alveolus; En: air space enlargement; P: pyknotic nucleus; R: respiratory bronchiole; T: terminal bronchiole; V: pulmonary vessels.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig4: PACAP aerosols reduce AMV-induced inflammatory infiltration and colliquative necrosis in alveolar and bronchiolar tissues. Histological analysis of paraffin-embedded lungs stained with hematoxylin and eosin from animals exposed to vehicle (a, b), AMV aerosols alone (c, d) or followed by inhalation of PACAP aerosols (e, f). The presence of edema (asterisks), the enlargement of air spaces (En), and mononuclear cell infiltration (arrowheads) as well as the pyknotic nuclei (P) are indicated. Representative photomicrographs showing the structure of the alveolar and bronchiolar tissues at low (100x; a, c, and e) and higher (400x; b, d, and f) magnification (n = 8 for each experimental group). A: alveolus; En: air space enlargement; P: pyknotic nucleus; R: respiratory bronchiole; T: terminal bronchiole; V: pulmonary vessels.
Mentions: As the AMV-dependent increase of lung resistance and its PACAP-mediated reversal may rely on structural changes of airways, we performed a histological study on lungs of treated rats. As expected lung sections of control rats stained with H&E showed normal bronchial lumen. Mucus was not abundant and smooth muscle (SM) layer had normal thickness (Figures 3(a) and 3(b)). In contrast, bronchial sections from rats exposed to vanadium alone showed various histological changes. AMV exposure induced an important accumulation of mucus leading to an obstructed aspect of bronchi. The obstruction appeared also enhanced by the observed hypertrophy of the smooth muscle layer (Figures 3(c) and 3(d)). These histological observations are further confirmed by morphometric analyses (Table 1) showing that the inhalation of vanadium decreased significantly the bronchial lumen diameter (BLD; 107.48 ± 4.77 versus 528.67 ± 9.19 μm for control animals, p < 0.01) and increased significantly the airway smooth muscle layer thickness (ASMT; 39.52 ± 0.89 μm versus 18.66 ± 0.35 μm for control animals, p < 0.01) compared to vehicle-treated animals. Features of cell desquamation were also detected in AMV-treated rats (Figures 3(c) and 3(d)). Lung sections from rats that received PACAP aerosols following vanadium inhalation exhibited a less obstructed bronchial lumen with reduced mucus accumulation (Figures 3(e) and 3(f)). Moreover, the BLD and the airway smooth muscle layer thickness (ASMT) values were significantly decreased compared to vanadium-treated group and were comparable to those of the control group (479.09 ± 24.82 and 16.76 ± 0.41 versus 528.67 ± 9.19 and 18.66 ± 0.35 μm, resp.; Table 1). Likewise, acute AMV exposure led to striking changes in alveolar tissue illustrated by the presence of edema, enlargement of air spaces, mononuclear cell infiltration, and colliquative necrosis characterized by numerous pyknotic nuclei (P) specifically in AMV-treated rats compared to control animals (Figures 4(a) and 4(d)). These AMV-associated histological alterations appeared strongly reduced in PACAP-treated animals (Figures 4(e) and 4(f)), suggesting a PACAP-counteracting action against the AMV-induced toxicity.

Bottom Line: 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-1α, MIP-2, and KC) and cytokines (IL-1α and TNF-α) 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Integrated Physiology, Science Faculty of Bizerte, Carthage University, 7021 Zarzouna, Tunisia ; National Institute of Health and Medical Research (INSERM), U982, 76821 Mont-Saint-Aignan Cedex, France ; Institute for Research and Innovation in Biomedicine (IRIB), Normandy University, 76821 Mont-Saint-Aignan Cedex, France ; Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen University, 76821 Mont-Saint-Aignan Cedex, France.

ABSTRACT
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/m(3)/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-1α, MIP-2, and KC) and cytokines (IL-1α and TNF-α) 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.

No MeSH data available.


Related in: MedlinePlus