UNIVERSIDADE FEDERAL DE SANTA CATARINA CENTRO DE CIÊNCIAS DA SAÚDE PROGRAMA DE PÓS-GRADUAÇÃO EM FARMÁCIA INFLUENCIA DA L-GLUTAMINA EXÓGENA NAS DEFESAS ANTIOXIDANTES E NA CURVA DE TOLERÂNCIA À GLICOSE, EM MODELO ANIMAL

L-glutamine (gln) is envolved in more metabolic process than any other amino acid, and has been classified as an essencial amino acid in demanding metabolic conditions when the oxidative stress is also present. Thus, the objective of this work is to investigate if gln would have some influence in endogen antioxidant defenses, as well as exert some effect on the glucose concentration and insulin secretion. The experimental models used in this work are: i) antioxidant properties through in vitro determinations; ii) ex vivo measurements of antioxidant defenses (reduced glutathione – GSH and total glutathione GT) and lipid peroxidation (TBARS); iii) glucose tolerance curves and insulin plasma concentration. The antioxidant defenses and the oxidative stress measurements were carried out in two experimental groups: i) by the chronic treatment of gln and/or glucose in the normal metabolism; ii) and in an acute oxidative stress model, induced by paraquat. For the glucose tolerance curves experiments gln was administrated in two different concentrations (1 M and 5 M), as well as an branched chain amino acid association and vitamin D3. Gln did not show an intrinsic potential as an antioxidant molecule in in vitro analysis. The antioxidant defenses were influenced by gln administration considering the period, the presence or absent of metabolic stress and also the tissue or fluid analyzed. When gln was administrated with glucose, in a chronic condition, it was able to maintain the GSH levels in the intestinal and hepatic tissues. Gln was effective increasing the GSH plasma levels in the presence of oxidative stress, but it did not promote the same significant effect on hepatic and renal tissues. Gln 1 M promoted a significant elevation on blood glucose concentration and a fast return to the zero time values, results obtained through the glucose tolerance curves. the administration of gln with the amino acid association or vitamin D3 showed a similar effect for both combinations and the initial elevation on glucose concentration was maintained until the last time observed. The insulin determination for the group receiving gln isolated was elevated, suggesting an effect of the molecule per se. The combination of the amino acid association with gln in the hyperglycemia model, induced an elevation of insulin concentration. Vitamin D3 administrated with glucose (hyperglycemia model) also showed an important augment on plasma insulin, but gln did not improve this effect. Therefore, gln may contribute to the increase or maintenance of the antioxidant defenses in a oxidative stress condition. Also, it could have a fast effect reducing blood glucose concentration when administrated with glucose, as a per se effect augmenting plasma insulin levels. The present work bring to the related literature the following summarized results: considering the experiments performed in animal models when all metabolic interactions are present, gln orally administrated in the concentration of 1 M had a relevant effect per se on the glutathione levels under an oxidative stress condition, and also on plasma insulin levels. The gln molecule also had a significative influence reducing blood glucose concentrations.