title: The role of glucagon-like peptide-2 on apoptosis, cell proliferation, and oxidant-antioxidant system at a mouse model of intestinal injury induced by tumor necrosis factor-alpha/actinomycin D.
abstract: Tumor necrosis factor-alpha (TNF-α) is a multifunctional cytokine, which has the ability to produce cytotoxicity via induction of cell death and cell cycle arrest. Blocking the synthesis of protective proteins through a transcriptional inhibitor such as actinomycin D (Act D) sensitizes many cell types to TNF-α toxicity. Teduglutide, h[Gly(2)]GLP-2, is a protease-resistant synthetic analog of glucagon-like peptide-2 (GLP-2) which is an intestinotrophic peptide. In this study, we evaluated this potential of GLP-2 on apoptosis, cell proliferation, and oxidant-antioxidant system on a mouse model of intestinal injury induced by TNF-α/Act D. The intestinal injury was induced by intraperitoneal administration of 15 μg/kg TNF-α and 800 μg/kg Act D per mouse. Animals were injected subcutaneously 200 μg/kg h[Gly(2)]GLP-2 every 12 h for 10 consecutive days prior to the administration of TNF-α and Act D. The model of intestinal injury induced by TNF-α/Act D, which is the new animal model for the intestinal disorders, was characterized by the degeneration of intestinal mucosa, an increase in apoptotic index, expression of active caspase-3, lipid peroxidation and glutathione (GSH) levels, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities; a decrease in cell proliferation and catalase (CAT) activity. h[Gly(2)]GLP-2 pretreatment prevented the TNF-α/Act D-induced oxidative injury by a significant reduction in the intestinal injury, apoptotic index, expression of active caspase-3, lipid peroxidation and GSH levels, GPx and SOD activities; a markedly increase in cell proliferation, and CAT activity. These results demonstrate that GLP-2 has a protective, antiapoptotic, proliferative, and antioxidant effects against to TNF-α/Act D-induced intestinal injury. It is suggested that GLP-2 may potentially be useful as a therapeutic agent in TNF-α-mediated intestinal disorders.
authors.affiliation: Department of Biology, Istanbul University, Istanbul, Turkey. parda@istanbul.edu.tr
authors.forename: Pelin
authors.initials: P
authors.lastname: Arda-Pirincci
authors.forename: Sehnaz
authors.initials: S
authors.lastname: Bolkent
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D003609:Dactinomycin; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005765:Gastrointestinal Agents / Q000494:pharmacology / Q000627:therapeutic use; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D007410:Intestinal Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016877:Oxidants / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha
chemical_list: D000975:Antioxidants; D005765:Gastrointestinal Agents; D053767:Glucagon-Like Peptide 2; D016877:Oxidants; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin