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.
Highlights
Hydrochloric acid (HCl) is considered one of the most hazardous chemicals and HCl exposure represents a threat to public health
Even though acute symptoms usually resolve in 3–7 days [5], HCl exposure has been shown to provoke a milder, persistent, and long-lasting inflammatory response, which has been related to the development of chronic lung injuries, including airway hyper-responsiveness [6], reactive airways dysfunction syndrome (RADS) [7], asthma-like conditions [8], and pulmonary fibrosis [9]
Thirty days post HCl instillation, severe changes in the lung parenchyma were observed in both young and adult mice when compared with the saline-instilled controls
Summary
Hydrochloric acid (HCl) is considered one of the most hazardous chemicals and HCl exposure represents a threat to public health. Even though acute symptoms usually resolve in 3–7 days [5], HCl exposure has been shown to provoke a milder, persistent, and long-lasting inflammatory response, which has been related to the development of chronic lung injuries, including airway hyper-responsiveness [6], reactive airways dysfunction syndrome (RADS) [7], asthma-like conditions [8], and pulmonary fibrosis [9]. In a public health screening of adults and children located within one mile of an HCl accidental spill, persistent abnormalities in spirometry were observed even ten months after the incident in more than 67% of the subjects [10]. Abnormal respiratory function was found in almost 30% of participants who did not report any breathing problems, suggesting that HCl-induced chronic lung injury may be underreported and that the real incidence of long-lasting complications after HCl exposure may be considerably higher
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