Erdosteine modulates surfactant-associated markers and preserves lung architecture in a preterm rat model compared with dexamethasone and betamethasone.

Preterm birth remains a major contributor to neonatal morbidity, primarily due to immature lung development and insufficient surfactant production. Although antenatal corticosteroids (ACS) are widely used to accelerate fetal lung maturation, concerns regarding their potential systemic effects have prompted the search for alternative or adjunctive agents. Erdosteine, a thiol-based compound with anti-inflammatory and antioxidant properties, may represent a promising candidate. Pregnant Sprague-Dawley rats were randomly assigned to four groups (n = 6 dams per group): control, dexamethasone (DEX), betamethasone (BET), and erdosteine (ERDO). All treatments were administered antenatally to the pregnant dams via intraperitoneal injection. DEX and BET were given on gestational days (GD) 16-18, while ERDO was administered on GD16-20. Preterm delivery was achieved by cesarean section on GD20. Lung tissues of pups born to treated dams were collected on postnatal day 5 (P5) and analyzed using histopathological and immunohistochemical methods, including Caspase-3, PCNA, ABCA3 (ATP-binding cassette subfamily A member 3), SFTPA1, AQP5, and SP-B. DEX and BET groups demonstrated lung architecture consistent with accelerated maturation, whereas ERDO preserved alveolar structure with only mild interstitial inflammation. Caspase-3 and PCNA expression were markedly increased in corticosteroid-treated groups but remained low in ERDO and control groups. Notably, ABCA3 expression was highest in the ERDO group across both compartments (p < 0.001). SFTPA1 expression was also more prominent in the interstitial compartment in the ERDO group. AQP5 and SP-B showed no significant expression in any group. Erdosteine demonstrated a biologically favorable profile characterized by reduced inflammatory response, preservation of lung architecture, and enhanced expression of key surfactant-related markers, particularly ABCA3. While not fully replicating the effects of antenatal corticosteroids, its anti-inflammatory and antioxidant properties suggest that it may serve as a supportive or complementary strategy for promoting fetal lung maturation. Further experimental and translational studies are warranted.