Teduglutide, a glucagon-like peptide 2 analogue: a novel protective agent with anti-apoptotic and anti-oxidant properties in mice with lung injury.
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.
Department of Biology, Faculty of Science, Istanbul University, 34134 Vezneciler, Istanbul, Turkey. parda@istanbul.edu.tr
Pelin
P
Arda-Pirincci
Fusun
F
Oztay
Bertan Boran
BB
Bayrak
Refiye
R
Yanardag
Sehnaz
S
Bolkent
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D015227:Lipid Peroxidation / Q000187:drug effects; D055370:Lung Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*
D000975:Antioxidants; D010455:Peptides; C494910:teduglutide