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| Author(s): |
Gabriela Freitas Pereira de Souza
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Química |
| Defense date: | 2011-07-15 |
| Examining board members: |
Silvana Bordin;
Renata Ferreira de Carvalho Leitão;
Carlos Roque Duarte Correia;
Adriana Souza Torsoni
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| Advisor: | Marcelo Ganzarolli de Oliveira |
| Abstract | |
In the present study, the nitric oxide (NO)-associated physiological actions obtained topically on the gastric mucosa and systemically in oral administrations of two NO donors-S-nitrosothiols (RSNOs), S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) were investigated in animal models. The topical ex vivo administration of RSNOs solutions on the gastric mucosa of Sprague-Dawley rats led to a dose-dependent increase in the gastric blood flow (GBF), measured by laser-Doppler flowmetry, with maximum GBF value c.a. 5 x higher than those obtained by equimolar applications of nitrite and nitrate solutions. The oral administration of GSNO and SNAC solutions was reflected in a time and dose-dependent increases in the plasma nitrite+nitrate level in Swiss mice. SNAC administration on non alcoholic fatty liver disease (NAFLD) induced in ob/ob or Swiss mice did not lead to significant changes in liver histology or in the mass gain pattern of the animals. The kinetic monitoring of the stability of aqueous GSNO and SNAC solutions as a function of pH and the identification of their decomposition products allowed to demonstrate that these RSNOs decay predominantly through mechanisms of acid or base-catalyzed hydrolysis, with maximum half-lives around the physiological pH. It was observed that Swiss mice fed a high-fat diet show an heterogeneous mass gain profile, which allows establishing a time-dependent correlation of obesity propensity and resistance with changes in the expressions of hypothalamic neuropeptides and in insulin resistance and glucose tolerance (AU) | |