Age-Dependent Chronic Lung Injury and Pulmonary Fibrosis following Single Exposure to Hydrochloric Acid

Abstract

Exposure to hydrochloric acid (HCl) represents a threat to public health. Children may inhale higher doses and develop greater injury because of their smaller airways and faster respiratory rate. We have developed a mouse model of pediatric exposure to HCl by intratracheally instilling p24 mice (mice 24 days old; 8–10 g) with 2 µL/g 0.1 N HCl, and compared the profile of lung injury to that in HCl-instilled adults (10 weeks old; 25–30 g) and their age-matched saline controls. After 30 days, alveolar inflammation was observed with increased proteinosis and mononuclear cells in the bronchoalveolar lavage fluid (BALF) in both HCl-instilled groups. Young p24 animals—but not adults—exhibited higher NLR family pyrin domain containing 3 (NLRP3) inflammasome levels. Increased amounts of Transforming Growth Factor-β (TGF-β) mRNA and its intracellular canonical and non-canonical pathways (p-Smad2 and p-ERK) were found in the lungs of both young and adult HCl-instilled mice. Constitutive age-related differences were observed in the levels of heat shock protein family (HSP70 and HSP90). HCl equally provoked the deposition of collagen and fibronectin; however, significant age-dependent differences were observed in the increase in elastin and tenascin C mRNA. HCl induced pulmonary fibrosis with an increased Ashcroft score, which was higher in adults, and a reduction in alveolar Mean Alveolar Linear Intercept (MALI). Young mice developed increased Newtonian resistance (Rn) and lower PV loops, while adults showed a higher respiratory system resistance and elastance. This data indicate that young p24 mice can suffer long-term complications from a single exposure to HCl, and can develop chronic lung injury characterized by a stronger persistent inflammation and lesser fibrotic pattern, mostly in the airways, differently from adults. Further data are required to characterize HCl time- and dose-dependent injury in young animals and to identify new key-molecular targets.

RETRACTED ARTICLE: MicroRNA-335-5p alleviates inflammatory response, airway fibrosis, and autophagy in childhood asthma through targeted regulation of autophagy related 5

“…A minimum of 400 cells were identified and counted under light microscopy (Olympus BX-46, Tokyo, Japan). Calculation of the mean number of monocyte-macrophage infiltration in each group was done at 200× magnification [ 21 ].…”

Dietary Phytoestrogens Ameliorate Hydrochloric Acid-Induced Chronic Lung Injury and Pulmonary Fibrosis in Mice

“…Radiation-challenged rats, treated with genistein, showed significant decreases in hydroxyproline and in levels of activated macrophages in lung tissue [41]. We and others have previously provided evidence implicating HSP90 in lung fibrogenesis [37,[42][43][44][45][46]. In the present study, we also report activation of HSP90 in mice receiving phytoestrogen-poor diet.…”

The Inflammasome NLR Family Pyrin Domain-Containing Protein 3 (NLRP3) as a Novel Therapeutic Target for Idiopathic Pulmonary Fibrosis

“…19 Age dependency of NLRP3 activation was also evaluated in p24 mice, indicating that age-dependent mechanism of inflammasome activation may be more complex during growth. 18…”