BACKGROUND & AIMS: Intestinal inflammation is associated with increased synthesis of nitric oxide, whereas inhibition of NO synthase (NOS) reduces experimental chronic intestinal inflammation. The aim of this study was to test the effects of NO blockers and donors on acute intestinal inflammation induced by Clostridium difficile toxin A in rat ileum. METHODS: Rats received NOS inhibitors or NO donors before measurement of toxin-mediated ileal secretion and permeability changes. Mucosal mast cell and neutrophil activity were measured by release of rat mast cell protease II and myeloperoxidase activity, respectively. RESULTS: NOS inhibitors augmented but an NO donor inhibited toxin A-mediated ileal secretion and permeability when given before but not after toxin administration. Neither an NOS inhibitor nor an NO donor had any effect on cholera toxin-mediated secretion. Mast cell degranulation and neutrophil infiltration occurred after injection of toxin A or an NOS inhibitor, whereas the NO donor blocked both toxin A effects. CONCLUSIONS: NOS inhibitors augmented and an NO donor blocked the intestinal effects of toxin A but not of cholera toxin. NO protects against toxin A by inhibition of intestinal mast cells and neutrophils, which are activated by toxin A, but not by cholera toxin.
BACKGROUND & AIMS:Intestinal inflammation is associated with increased synthesis of nitric oxide, whereas inhibition of NO synthase (NOS) reduces experimental chronic intestinal inflammation. The aim of this study was to test the effects of NO blockers and donors on acute intestinal inflammation induced by Clostridium difficile toxin A in rat ileum. METHODS:Rats received NOS inhibitors or NO donors before measurement of toxin-mediated ileal secretion and permeability changes. Mucosal mast cell and neutrophil activity were measured by release of ratmast cell protease II and myeloperoxidase activity, respectively. RESULTS: NOS inhibitors augmented but an NO donor inhibited toxin A-mediated ileal secretion and permeability when given before but not after toxin administration. Neither an NOS inhibitor nor an NO donor had any effect on cholera toxin-mediated secretion. Mast cell degranulation and neutrophil infiltration occurred after injection of toxin A or an NOS inhibitor, whereas the NO donor blocked both toxin A effects. CONCLUSIONS: NOS inhibitors augmented and an NO donor blocked the intestinal effects of toxin A but not of cholera toxin. NO protects against toxin A by inhibition of intestinal mast cells and neutrophils, which are activated by toxin A, but not by cholera toxin.
Authors: G M Calderón; J Torres-López; T J Lin; B Chavez; M Hernández; O Muñoz; A D Befus; J A Enciso Journal: Infect Immun Date: 1998-06 Impact factor: 3.441
Authors: David Rojo; María J Gosalbes; Rafaela Ferrari; Ana E Pérez-Cobas; Ester Hernández; Rosa Oltra; Javier Buesa; Amparo Latorre; Coral Barbas; Manuel Ferrer; Andrés Moya Journal: ISME J Date: 2015-03-10 Impact factor: 10.302
Authors: Tor C Savidge; Petri Urvil; Numan Oezguen; Kausar Ali; Aproteem Choudhury; Vinay Acharya; Irina Pinchuk; Alfredo G Torres; Robert D English; John E Wiktorowicz; Michael Loeffelholz; Raj Kumar; Lianfa Shi; Weijia Nie; Werner Braun; Bo Herman; Alfred Hausladen; Hanping Feng; Jonathan S Stamler; Charalabos Pothoulakis Journal: Nat Med Date: 2011-08-21 Impact factor: 53.440