Erdosteine as a Novel Modulator of Surfactant Maturation: A Comparative Analysis With Dexamethasone and Betamethasone in a Preterm Rat Lung Model

Background: Preterm birth remains a major contributor to neonatal morbidity, largely due to immature lung structure and insufficient surfactant production. This study evaluated the potential of erdosteine as an alternative or complementary agent to antenatal corticosteroids (ACS) by comparing its effects on lung maturation with dexamethasone (DEX) and betamethasone (BET) in a preterm rat model. Particular emphasis was placed on two anatomical compartments: the interstitial area and the bronchiolar epithelium. Methods: Preterm delivery was induced by cesarean section on gestational day 16 in Sprague–Dawley rats. Newborn pups were assigned to four groups: control, DEX, BET, and erdosteine (ERDO). Lung tissues collected on postnatal day 5 underwent histopathological evaluation and immunohistochemical analysis of Caspase-3, PCNA, ABCA3, SFTPA1, AQP5, and SP-B. Staining intensity was semi-quantitatively scored in both compartments. Results: DEX and BET produced lung histology that closely resembled normal tissue architecture, whereas ERDO resulted in only mild interstitial mononuclear infiltration. Caspase-3 and PCNA expression markedly increased in both compartments of the DEX and BET groups but remained low in ERDO and controls. ABCA3 expression was most pronounced in the ERDO group across both compartments (p < 0.001), surpassing even the corticosteroid groups. SFTPA1 was highest in the interstitial area of ERDO-treated pups, while bronchiolar epithelial staining was more evident in the control and DEX groups. AQP5 and SP-B did not show significant positivity in any group. Conclusions: Erdosteine demonstrated a supportive and biologically meaningful pattern of lung maturation, with reduced inflammation and balanced cellular turnover, accompanied by a notable increase in surfactant-related markers—particularly ABCA3. While not replicating all effects of antenatal corticosteroids, its favorable molecular profile and absence of corticosteroid-associated tissue alterations highlight its potential as a gentler, complementary approach to promoting pulmonary readiness in preterm neonates. These findings warrant further investigation in broader experimental and clinical settings.