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Updated: Jul 11, 2026
Induction of Mouse Lung Injury by Endotracheal Injection of Bleomycin
Published on: April 30, 2019
Glycogen synthase kinase-3beta inhibition attenuates the development of bleomycin-induced lung injury
S Cuzzocrea1, T Genovese, E Mazzon
1Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy. salvator@unime.it
Abstract:
Glycogen synthase kinase-3 (GSK-3) is an ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and has recently been implicated in the pathophysiology of a number of diseases. The aim of this study is to investigate the effects of TDZD-8, a potent and selective GSK-3beta inhibitor, on the development of lung injury caused by administration of bleomycin (BLM). Mice subjected to intra-tracheal administration of BLM developed significant lung injury characterized by marked neutrophil infiltration and tissue edema. An increase in immunoreactivity to nitrotyrosine, iNOS, TNF-alpha and IL-1beta was also observed in the lungs of BLM-treated mice. In contrast, administration of BLM-treated mice with TDZD-8 (1 mg/kg daily) significantly reduced (I) the degree of lung injury, (II) the increase in staining (immunohistochemistry) for myeloperoxidase (MPO), nitrotyrosine, iNOS, TNF-alpha and IL-1beta and (III) the degree of apoptosis, as evaluated by Bax and Bcl-2 immunoreactivity and TUNEL staining. Taken together, these results clearly demonstrate treatment with the GSK-3beta inhibitor TDZD-8 reduces the development of lung injury and inflammation induced by BLM in mice.
Insights
The GSK-3beta inhibitor TDZD-8 significantly reduced lung injury and inflammation in mice treated with bleomycin. This suggests TDZD-8 may be a potential therapeutic for bleomycin-induced lung damage.
Area of Science:
- Biochemistry
- Pharmacology
- Pulmonology
Background:
- Glycogen synthase kinase-3 (GSK-3) is a key kinase involved in numerous cellular functions.
- Dysregulation of GSK-3 is implicated in various disease pathologies.
- Bleomycin (BLM)-induced lung injury is a model for studying inflammatory lung diseases.
Purpose of the Study:
- To investigate the therapeutic potential of TDZD-8, a selective GSK-3beta inhibitor, against BLM-induced lung injury.
- To evaluate the impact of TDZD-8 on inflammatory markers and apoptosis in the lungs.
Main Methods:
- Mice were administered intra-tracheal bleomycin to induce lung injury.
- TDZD-8 was administered daily to BLM-treated mice.
- Lung injury, neutrophil infiltration, edema, inflammatory markers (nitrotyrosine, iNOS, TNF-alpha, IL-1beta), and apoptosis (Bax, Bcl-2, TUNEL) were assessed.
Main Results:
- BLM administration caused significant lung injury, characterized by neutrophil infiltration, edema, and increased inflammatory markers.
- TDZD-8 treatment markedly reduced the severity of lung injury and associated inflammation.
- TDZD-8 significantly decreased apoptosis in the lung tissue of BLM-treated mice.
Conclusions:
- The GSK-3beta inhibitor TDZD-8 effectively mitigates bleomycin-induced lung injury and inflammation in mice.
- TDZD-8 demonstrates potential as a therapeutic agent for inflammatory lung diseases like BLM-induced lung injury.
