Teduglutide is a long-acting synthetic analogue of human
glucagon-like peptide-2 (GLP-2). GLP-2 regulates cell proliferation and apoptosis as well as normal physiology in the gastrointestinal tract. In the present study, possible cytoprotective and reparative effects of
teduglutide were analyzed on a mouse model with
lung injury induced by
tumor necrosis factor-alpha (TNF-α) and
actinomycin D (Act D). BALB/c mice were divided into six groups: control mice (I), mice injected intraperitoneally with 15 μg/kg TNF-α (II), 800 μg/kg Act D (III), Act D 2 min prior to TNF-α administration with the same doses (IV), mice injected subcutaneously with 200 μg/kg
teduglutide every 12h for 10 consecutive days (V), and mice given Act D 2 min prior to TNF-α administration on day 11 after receiving
teduglutide for 10 days (VI). The TNF-α/Act D administration made the lung a sensitive organ to damage. Mice lung subjected to TNF-α/Act D were characterized by the disruption of alveolar wall, induced pulmonary endothelial/epithelial cell apoptosis and expression of active
caspase-3. These mice exhibited an increase in lipid peroxidation,
glutathione levels, and activities of
myeloperoxidase,
superoxide dismutase,
catalase,
glutathione peroxidase and
xanthine oxidase, as well as reduced
tissue factor and
sodium-potassium/ATPase activities.
Teduglutide pretreatment regressed the structural damage, cell apoptosis and oxidative stress by reducing lipid peroxidation in mice received TNF-α/Act D. GLP-2 receptors were present on the cell membrane of type II pneumocytes and interstitial cells. Thus,
teduglutide can be suggested as a novel
protective agent, which possesses anti-apoptotic and
anti-oxidant properties, against
lung injury.