Molsidomine decreases hyperoxia-induced lung injury in neonatal rats

Pediatr Res. 2023 Oct;94(4):1341-1348. doi: 10.1038/s41390-023-02643-w. Epub 2023 May 13.

Abstract

Background: The study's objective is to evaluate if Molsidomine (MOL), an anti-oxidant, anti-inflammatory, and anti-apoptotic drug, is effective in treating hyperoxic lung injury (HLI).

Methods: The study consisted of four groups of neonatal rats characterized as the Control, Control+MOL, HLI, HLI + MOL groups. Near the end of the study, the lung tissue of the rats were evaluated with respect to apoptosis, histopathological damage, anti-oxidant and oxidant capacity as well as degree of inflammation.

Results: Compared to the HLI group, malondialdehyde and total oxidant status levels in lung tissue were notably reduced in the HLI + MOL group. Furthermore, mean superoxide dismutase, glutathione peroxidase, and glutathione activities/levels in lung tissue were significantly higher in the HLI + MOL group as compared to the HLI group. Tumor necrosis factor-α and interleukin-1β elevations associated with hyperoxia were significantly reduced following MOL treatment. Median histopathological damage and mean alveolar macrophage numbers were found to be higher in the HLI and HLI + MOL groups when compared to the Control and Control+MOL groups. Both values were increased in the HLI group when compared to the HLI + MOL group.

Conclusions: Our research is the first to demonstrate that bronchopulmonary dysplasia may be prevented through the protective characteristics of MOL, an anti-inflammatory, anti-oxidant, and anti-apoptotic drug.

Impact: Molsidomine prophylaxis significantly decreased the level of oxidative stress markers. Molsidomine administration restored the activities of antioxidant enzymes. Molsidomine prophylaxis significantly reduced the levels of inflammatory cytokines. Molsidomine may provide a new and promising therapy for BPD in the future. Molsidomine prophylaxis decreased lung damage and macrophage infiltration in the tissue.

MeSH terms

  • Animals
  • Animals, Newborn
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / metabolism
  • Hyperoxia* / pathology
  • Lung
  • Lung Injury* / drug therapy
  • Lung Injury* / etiology
  • Lung Injury* / prevention & control
  • Molsidomine / pharmacology
  • Molsidomine / therapeutic use
  • Oxidants / pharmacology
  • Oxidative Stress
  • Rats
  • Rats, Wistar

Substances

  • Antioxidants
  • Molsidomine
  • Oxidants
  • Anti-Inflammatory Agents