title: Glucagon-like peptide 2 counteracts the mucosal damage and the neuropathy induced by chronic treatment with cisplatin in the mouse gastric fundus.
abstract: BACKGROUND
  Glucagon-like peptide-2 (GLP-2) is a pleiotropic hormone synthesized and secreted by the enteroendocrine 'L' cells able to exert intestine-trophic and anti-inflammatory effects. The antineoplastic drug cisplatin causes gastrointestinal alterations with clinical symptoms (nausea and vomiting) that greatly affect the therapy compliance. Experimentally, it has been reported that chronic cisplatin treatment caused mucosal damage and enteric neuropathy in the rat colon.
  
  
  METHODS
  We investigated, through a combined immunohistochemical and functional approach, whether [Gly(2) ]GLP-2, a GLP-2 analog, was able to counteract the detrimental effects of long-term cisplatin administration in the mucosa and myenteric neurons of mouse gastric fundus.
  
  
  RESULTS
  Morphological experiments showed a reduction in the epithelium thickness in cisplatin-treated mice, which was prevented by [Gly(2) ]GLP-2 co-treatment. Immunohistochemistry demonstrated that cisplatin caused a significant decrease in myenteric neurons, mainly those expressing neuronal nitric oxide synthase (nNOS), that was prevented by [Gly(2) ]GLP-2 co-treatment. In the functional experiments, [Gly(2) ]GLP-2 co-treatment counteracted the increase in amplitude of the neurally induced contractions observed in strips from cisplatin-treated animals. The NO synthesis inhibitor L-N(G) -nitro arginine caused an increase in amplitude of the contractile responses that was greater in preparations from cisplatin+[Gly(2) ]GLP-2 treated mice compared to the cisplatin-treated ones.
  
  
  CONCLUSIONS
  The results demonstrate that in cisplatin long-term treated mice [Gly(2) ]GLP-2 is able to counteract both the mucosal gastric fundus damage, by preventing the epithelium thickness decrease, and the neuropathy, by protecting the nNOS neurons. Taken together, the present data suggest that [Gly(2) ]GLP-2 could represent an effective strategy to overcome the distressing gastrointestinal symptoms present during the anti-neoplastic therapy.
authors.affiliation: Department of Experimental and Clinical Medicine, Histology and Embryology Research Unit, University of Florence, Florence, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pini
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Garella
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Idrizaj
authors.affiliation: Department of Experimental and Clinical Medicine, Histology and Embryology Research Unit, University of Florence, Florence, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Calosi
authors.affiliation: Department of Experimental and Clinical Medicine, Section of Physiological Sciences, University of Florence, Florence, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Baccari
authors.affiliation: Department of Experimental and Clinical Medicine, Histology and Embryology Research Unit, University of Florence, Florence, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Vannucchi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D015153:Blotting, Western; D002945:Cisplatin / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology*; D007150:Immunohistochemistry; D007418:Intestinal Pseudo-Obstruction / Q000139:chemically induced*; D051379:Mice; D008810:Mice, Inbred C57BL; D009197:Myenteric Plexus / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D053767:Glucagon-Like Peptide 2; D010455:Peptides; C494910:teduglutide; D002945:Cisplatin
keywords: antineoplastic drug; gastric epithelium; myenteric plexus; nitrergic neurons; pleiotropic intestinal hormone