PMID- 21153865 OWN - NLM STAT- MEDLINE DCOM- 20110715 LR - 20211020 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 350 IP - 1-2 DP - 2011 Apr TI - 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. PG - 13-27 LID - 10.1007/s11010-010-0678-0 [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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-alpha/Act D. The intestinal injury was induced by intraperitoneal administration of 15 mug/kg TNF-alpha and 800 mug/kg Act D per mouse. Animals were injected subcutaneously 200 mug/kg h[Gly(2)]GLP-2 every 12 h for 10 consecutive days prior to the administration of TNF-alpha and Act D. The model of intestinal injury induced by TNF-alpha/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-alpha/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-alpha/Act D-induced intestinal injury. It is suggested that GLP-2 may potentially be useful as a therapeutic agent in TNF-alpha-mediated intestinal disorders. FAU - Arda-Pirincci, Pelin AU - Arda-Pirincci P AD - Department of Biology, Istanbul University, Istanbul, Turkey. parda@istanbul.edu.tr FAU - Bolkent, Sehnaz AU - Bolkent S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101214 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Antioxidants) RN - 0 (Gastrointestinal Agents) RN - 0 (Glucagon-Like Peptide 2) RN - 0 (Oxidants) RN - 0 (Tumor Necrosis Factor-alpha) RN - 1CC1JFE158 (Dactinomycin) SB - IM MH - Animals MH - Antioxidants/*metabolism MH - *Apoptosis/drug effects/physiology MH - *Cell Proliferation/drug effects MH - Dactinomycin MH - Disease Models, Animal MH - Drug Evaluation, Preclinical MH - Gastrointestinal Agents/pharmacology/therapeutic use MH - Glucagon-Like Peptide 2/pharmacology/*physiology/therapeutic use MH - Intestinal Diseases/chemically induced/drug therapy/metabolism/*pathology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Oxidants/*metabolism MH - Tumor Necrosis Factor-alpha EDAT- 2010/12/15 06:00 MHDA- 2011/07/16 06:00 CRDT- 2010/12/15 06:00 PHST- 2010/06/28 00:00 [received] PHST- 2010/12/02 00:00 [accepted] PHST- 2010/12/15 06:00 [entrez] PHST- 2010/12/15 06:00 [pubmed] PHST- 2011/07/16 06:00 [medline] AID - 10.1007/s11010-010-0678-0 [doi] PST - ppublish SO - Mol Cell Biochem. 2011 Apr;350(1-2):13-27. doi: 10.1007/s11010-010-0678-0. Epub 2010 Dec 14.