CEDIE   05498
CENTRO DE INVESTIGACIONES ENDOCRINOLOGICAS "DR. CESAR BERGADA"
Unidad Ejecutora - UE
artículos
Título:
Inhibition of Nitric Oxide Generation in Mononuclear Splenocytes from Multiple-Low-Dose-Streptozotocin Diabetic Mice
Autor/es:
L. KARABATAS; C. PASTORALE
Revista:
JMED Research
Editorial:
IBIMA Publishing
Referencias:
Lugar: king of Prussia, Pennsylvania; Año: 2013 vol. 2013 p. 1 - 16
ISSN:
2333-2395
Resumen:
Mice injected with multiple low dose of streptozotocin (mld-SZ) or transferred with mononuclear splenocytes (MS) from mld-SZ donors constitute animal models that allow the study of autoimmune diabetes. Mld-SZ mice show a progressive beta-cell destruction iniciated during non-specific islet inflammation involving free radicals as nitric oxide (NO°). Pharmacological inhibitors of NO° synthase delay or prevent the outbreak of disease, but have deleterious side effects when administered in vivo. The aim of this study, was to clarify the role of NO?? on the ability of MS from mld-SZ mice to impair insulin secretion. Also, we investigated the beneficial effects of using NO?? synthase inhibitors in vitro on anti-beta cells agression.in vivo. The aim of this study, was to clarify the role of NO?? on the ability of MS from mld-SZ mice to impair insulin secretion. Also, we investigated the beneficial effects of using NO?? synthase inhibitors in vitro on anti-beta cells agression.in vitro on anti-beta cells agression. Methods: NO° was measured in cultured MS and islets of Langerhans isolated from mice at days 4 to 16 after the first mld-SZ injection. MS were also cultured with an inhibitor of NO° production, L-NG-monomethyl-arginine (L-NMMA), and then: a) injected in syngeneic mice to evaluate their insulin secretion patterns or b) co-cultured with islet cells to estimate the capacity of MS to exert in vitro cellular immune aggression. Results: Cultured islets of Langerhans and MS from mld-SZ mice showed increases in NO° production (p>0.05). MS from mld-SZ mice, obtained at days 4 to 9 and precultured with L-NMMA showed ameliorations in their deleterious effect on insulin secretion from transferred recipient mice and from cocultured islet cells (p<0.05). Conclusions: These results suggest that the inhibition of NO° production ?in vitro? reduced the aggressive capacity of MS from mld-SZ mice avoiding, at least in part, beta cell damage and destruction.NO° was measured in cultured MS and islets of Langerhans isolated from mice at days 4 to 16 after the first mld-SZ injection. MS were also cultured with an inhibitor of NO° production, L-NG-monomethyl-arginine (L-NMMA), and then: a) injected in syngeneic mice to evaluate their insulin secretion patterns or b) co-cultured with islet cells to estimate the capacity of MS to exert in vitro cellular immune aggression. Results: Cultured islets of Langerhans and MS from mld-SZ mice showed increases in NO° production (p>0.05). MS from mld-SZ mice, obtained at days 4 to 9 and precultured with L-NMMA showed ameliorations in their deleterious effect on insulin secretion from transferred recipient mice and from cocultured islet cells (p<0.05). Conclusions: These results suggest that the inhibition of NO° production ?in vitro? reduced the aggressive capacity of MS from mld-SZ mice avoiding, at least in part, beta cell damage and destruction.G-monomethyl-arginine (L-NMMA), and then: a) injected in syngeneic mice to evaluate their insulin secretion patterns or b) co-cultured with islet cells to estimate the capacity of MS to exert in vitro cellular immune aggression. Results: Cultured islets of Langerhans and MS from mld-SZ mice showed increases in NO° production (p>0.05). MS from mld-SZ mice, obtained at days 4 to 9 and precultured with L-NMMA showed ameliorations in their deleterious effect on insulin secretion from transferred recipient mice and from cocultured islet cells (p<0.05). Conclusions: These results suggest that the inhibition of NO° production ?in vitro? reduced the aggressive capacity of MS from mld-SZ mice avoiding, at least in part, beta cell damage and destruction.in vitro cellular immune aggression. Results: Cultured islets of Langerhans and MS from mld-SZ mice showed increases in NO° production (p>0.05). MS from mld-SZ mice, obtained at days 4 to 9 and precultured with L-NMMA showed ameliorations in their deleterious effect on insulin secretion from transferred recipient mice and from cocultured islet cells (p<0.05). Conclusions: These results suggest that the inhibition of NO° production ?in vitro? reduced the aggressive capacity of MS from mld-SZ mice avoiding, at least in part, beta cell damage and destruction.Conclusions: These results suggest that the inhibition of NO° production ?in vitro? reduced the aggressive capacity of MS from mld-SZ mice avoiding, at least in part, beta cell damage and destruction.?in vitro? reduced the aggressive capacity of MS from mld-SZ mice avoiding, at least in part, beta cell damage and destruction.