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  • Basic Science Article
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Molsidomine decreases hyperoxia-induced lung injury in neonatal rats

Pediatric Research volume 94, pages 1341–1348 (2023)Cite this article

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.

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Fig. 1: Histopathological staining of lung tissues.
Fig. 2: Quantitative analysis of hyperoxic lung injury.
Fig. 3: The administration of MOL reduced the alveolar macrophage number (thin black arrows).
Fig. 4: Immunohistochemical staining of Caspase-3 revealed the antiapoptotic effect of MOL in the hyperoxia-induced lung injury model.
Fig. 5: TUNEL staining of rat lung tissue showed the apoptotic death of nuclear cells (purple arrows) in the model and immunohistochemical staining of TUNEL confirmed the antiapoptotic effect of MOL in the hyperoxia-induced lung injury model.

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Data availability

All datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pediatrics, Inonu University School of Medicine, Malatya, Turkey

    Mehmet Aslan

  2. Division of Neonatology, Department of Pediatrics, Inonu University School of Medicine, Malatya, Turkey

    Ismail Kursat Gokce, Hatice Turgut, Mehmet Fatih Deveci, Huseyin Kaya & Ramazan Ozdemir

  3. Department of Physiology, Inonu University School of Medicine, Malatya, Turkey

    Suat Tekin & Kevser Tanbek

  4. Department of Histology and Embryology, Inonu University School of Medicine, Malatya, Turkey

    Asli Cetin Taslidere & Cemile Ceren Gul

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Contributions

R.O. and I.K.G. participated in the study design, analyzed data, performed experiments, interpreted results, and edited the manuscript. S.T. and A.C.T. participated in the study design, prepared figures, interpreted results, analyzed data, performed experiments, and edited the manuscript. K.T. and C.C.G. contributed to conceptualizing the study, interpreted results, performed experiments, and prepared figures. H.T., M.F.D., H.K., and M.A. conceptualized the study and its design, interpreted results, performed experiments and edited the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ramazan Ozdemir.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the Ethical Committee of Experimental Animals of the Faculty of Medicine in Inonu University, at which the studies were conducted.

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Aslan, M., Gokce, I.K., Turgut, H. et al. Molsidomine decreases hyperoxia-induced lung injury in neonatal rats. Pediatr Res 94, 1341–1348 (2023). https://doi.org/10.1038/s41390-023-02643-w

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