Inhaled sulfur dioxide causes pulmonary and systemic inflammation leading to fibrotic respiratory disease in a rat model of chemical-induced lung injury

Anti-inflammatory and anti-fibrotic treatment in a rodent model of acute lung injury induced by sulfur dioxide

“…Rats were subjected to a single exposure of SO 2 -gas mixture for 10 min. The SO 2 concentration in the inhalation tower was monitored and the experiments were conducted in a designated fume hood for toxic gas exposures [15]. In the meantime, control animals were retained in their cages while breathing room air for 10 min (not placed in individual containers).…”

“…The dose of DEX (dexamethasone 21-phosphate disodium salt, Sigma-Aldrich, St. Louis, MO) was selected based on the results of previous studies [15,21,22]. DEX was dissolved in NaCl (0.9% NaCl in water) and a volume of 500 ll was administered intraperitoneally (i.p.)…”

“…In a previous study using Sprague-Dawley rats [15], the acute pulmonary response to inhaled SO 2 was shown to involve tissue injury, acute neutrophilic lung inflammation and hyperreactivity of large airways. The acute response was followed by a long-term inflammation dominated by macrophages and eosinophils, and an upregulation of the profibrotic cytokine TGF-b1.…”

“…This treatment was, however, insufficient for complete protection against 1) the pulmonary toxicity (AHR and fibrosis), 2) animal body weight-loss and 3) cardiopulmonary effects (DEX-treatment did not reduce the increased heart-weight detected in the SO 2 -exposed animals). The reducing effects of DEX on AHR were inconsistent, indicating that hyperreactive airways may only partly be linked to acute cellular inflammation [15].…”

“…An ideal treatment against SO 2 -induced lung injury includes protection against both acute and long-term effects. From the previous animal studies, it is clear that corticosteroids are generally beneficial in reducing adverse physiological effects induced by inflammatory responses, but also that alternative treatment approaches targeting other mechanisms such as pulmonary fibrosis in the pathogenesis are required for comprehensive protection [15,19,20]. It should also be emphasized that the lung injuries caused by toxic compounds depend on the specific interactions (due to physicochemical properties, e.g., water solubility, pH and oxidation strength) between the chemical, and biological tissues, i.e., the mechanisms leading to inflammation and hyperreactive airways are expected to differ between toxic irritant chemicals.…”