Avaliação toxicologica e farmacologica do complemento nutricional "TK3" / "TK3" : association between L-tryptophan and thymine toxicological and pharmacological studies

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

The nutritional supplement ?TK3? was originally studied by a German biochemist, Mr. Friedrich Lavitcshka, who first associated L-tryptophan and thymine, in a liquid formula, in 1969. His early studies using experimental tar-induced skin cancer models were not published even though they seemed to confirm the benefits reported by informal use of such association at that time. These reports suggested some pharmacological effects beyond the nutritional one. The toxicological evaluation of this new association of substances, as part of its pre-clinical trial, revealed: 1. ?In vitro? studies: no citotoxicity activity of ?TK3? on normal (fibroblasts) and cancer human cells; 2. ?In vivo? acute studies: acute administration of ?TK3? (5 g/Kg, p.o. and 2g/Kg, i.p.) in Wistar rats revealed no signs of systemic toxicity or impending death; 3. ?in vivo? sub-chronic studies: 90 day repeated-dose study of ?TK3? (100 mg/Kg, 300 mg/Kg and 1000 mg/Kg, p.o.) in Wistar rats of both sexes revealed no clinical signs of toxicity, confirmed by both histopathological and biochemical analysis. The pharmacological screening of this nutritional supplement revealed: 1. In the ethanol-induced gastric ulcer experimental model in rats, the treatment with ?TK3? (1000mg/Kg, p.o.) reduced the ulcerative ulcer index (86.2%). This antiulcerogenic activity was superior to the ones presented by the isolated components administrated individually (L-tryptophan: 400mg/Kg [61.5%] and thymine: 400mg/Kg [+30.8%]); 2. In the evaluation of gastric secretion through pyloric ligation model in rats, the treatment with ?TK3? (1000 mg/Kg, i.d.) had no significant effect over the gastric juice volume, nor the pH or hydrogenionic concentration of gastric content; 3. In the evaluation of possible gastric cytoprotective mechanisms of action, pre-treatment of experimental rats with indomethacin (5 mg/Kg, p.o.) did not inhibit the antiulcerogenic effect of ?TK3? (1000 mg/Kg, p.o.) in the ethanol induced ulcer model; 4. Similarly, pre-treatment of experimental rats with L-NAME (5 mg/Kg, i.v.) did not inhibit the antiulcerogenic effect of ?TK3? (1000 mg/Kg, p.o.) in the ethanol induced ulcer model; 5. Finally, pre-treatment of experimental rats with NEM (10 mg/Kg, s.c.) decreased 50% of the antiulcerogenic effect of ?TK3? (1000 mg/Kg, p.o.) in the ethanol induced ulcer model, suggesting the participation of endogenous non-protein SH-containing compounds. However, as this reduction was not complete, there seems to be more aspects involved in this mechanism of action.

ASSUNTO(S)

timina wistar triptofano toxicity mice camundongos ratos wistar thymine rats toxicidade tryptophan

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