RESUMO
The effect of the administration of a whey protein isolate (WPI) and collagen hydrolysates on ethanol-induced ulcerative lesions was studied in rats. WPI and bovine or porcine collagen hydrolysate (BCH and PCH, respectively) were given to rats by gavage. In acute experiments, (single-dose) physiological saline (10 mL/kg of body weight) was used as the negative control, and carbenoxolone (200 mg/kg of body weight) was used as a positive control. Ethanol (1 mL per 250-g rat) was also given by gavage. These treatments reduced the ulcerative lesion index (ULI) in a range of 40-77%, depending on the dosage. Some mixtures of WPI with either PCH or BCH provided results that suggested synergisms between WPI and the collagen hydrolysates. For example, WPI/BCH (in the proportion of 375:375 mg/kg of body weight) decreased ULI by 64%. The mechanism for mucosal protection involved a decrease in plasma gastrin (approximately 40%), a significant increase (50-267%) in mucus production, and a reduction in ULI (percentage) when intragastric administrations were performed after in vivo alkylation by N-ethylmaleimide. Results suggest that gastrin, sulfhydryl substances, and some mechanisms related to mucus production are all involved in gastric ulcer protection against ethanol. The collagen hydrolysates (both PCH and BCH) presented a stronger effect on mucus production; on the other hand, the effect of WPI was also dependent on sulfhydryl compounds, resulting in a more protective effect when the two proteins were administered together.
Assuntos
Antiulcerosos/uso terapêutico , Colágeno/uso terapêutico , Mucosa Gástrica/efeitos dos fármacos , Proteínas do Leite/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Estômago/efeitos dos fármacos , Alquilação , Animais , Antiulcerosos/farmacologia , Carbenoxolona/uso terapêutico , Bovinos , Colágeno/metabolismo , Colágeno/farmacologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Etanol , Etilmaleimida/metabolismo , Mucosa Gástrica/patologia , Gastrinas/sangue , Hidrólise , Masculino , Proteínas do Leite/farmacologia , Muco/metabolismo , Ratos , Ratos Wistar , Estômago/patologia , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Compostos de Sulfidrila/metabolismo , Suínos , Proteínas do Soro do LeiteRESUMO
Tryptophan is required in the pineal gland for the formation of serotonin, precursor of melatonin biosynthesis. The level of this amino acid in the serum and in the pineal gland of the rat undergoes a circadian rhythm, and reduced plasma tryptophan concentration decreases secretion of melatonin in humans. Tryptophan is transported into the cells by the long chain neutral amine acid system T and by the aromatic amino acid system T. The high affinity component of [(3)H]tryptophan uptake was studied in pinealocytes of the rat. Inhibition was observed in the presence of phenylalanine or tyrosine, but not in the presence of neutral amino acids, alanine, glycine, serine, lysine or by 2-aminobicyclo[2,2,1]-heptane-2-carboxylic acid, a substrate specific for system L. The transport of tryptophan was temperature-dependent and trans-stimulated by phenylalanine and tyrosine, but was energy-, sodium-, chloride-, and pH-independent. In addition, the sulphydryl agent N-ethylmaleimide did not modify the high affinity transport of tryptophan in pinealocytes. The kinetic parameters were not significantly different at 12:00 as compared to 24:00 h. The treatment with the inhibitor of tryptophan hydroxylase, p-chlorophenylalanine, produced an increase in the maximal velocity of the uptake and a reduction in the affinity at 12:00, but not at 24:00 h, probably indicating that during the day, the formation of serotonin in the pineal gland is favoured by elevating the uptake of tryptophan, whereas at 24:00 h other mechanisms, such as induction of enzymes are taking place. High affinity tryptophan uptake in the rat pineal gland occurs through system T and is upregulated during the day when the availability of serotonin is reduced.