In the present study, we aimed to investigate whether chronic oral glutamine (Gln) supplementation may alter metabolic parameters and the inflammatory profile in overweight and obese humans as well as whether Gln may modulate molecular pathways in key tissues linked to the insulin action in rats. Thirty-nine overweight/obese volunteers received 30 g of Gln or alanine (Ala-control) for 14 days. Body weight (BW), waist circumference (WC), hormones, and pro-inflammatory markers were evaluated. To investigate molecular mechanisms, Gln or Ala was given to Wistar rats on a high-fat diet (HFD), and metabolic parameters, euglycemic hyperinsulinemic clamp with tracers, and Western blot were done. Gln reduced WC and serum lipopolysaccharide (LPS) in overweight volunteers. In the obese group, Gln diminished WC and serum insulin. There was a positive correlation between the reduction on WC and LPS. In rats on HFD, Gln reduced adiposity, improved insulin action and signaling, and reversed both defects in glucose metabolism in the liver and muscle. Gln supplementation increased muscle glucose uptake and reversed the increased hepatic glucose production, in parallel with a reduced glucose uptake in adipose tissue. This insulin resistance in AT was accompanied by enhanced IRS1 O-linked-glycosamine association in this tissue, but not in the liver and muscle. These data suggest that Gln supplementation leads to insulin resistance specifically in adipose tissue via the hexosamine pathway and reduces adipose mass, which is associated with improvement in the systemic insulin action. Thus, further investigation with Gln supplementation should be performed for longer periods in humans before prescribing as a beneficial therapeutic approach for individuals who are overweight and obese.
This study aimed to characterize and compare the histopathological and immunohistochemical effects of OncoTherad therapy associated or not with chemotherapy with 5-Fluouracil in the chemically induced Colorectal Cancer (CRC) and establish the possible mechanisms of action of these therapeutic associations involving the signaling pathway of the Toll-like Receptor 4. CRC was induced by dimethylhydrazine (DMH) in C57BL/6J mice. Animals from treated groups received, once a week, 15 mg/Kg of 5-FU or 25 mg/Kg of OncoTherad, over 10 weeks. Tissues were collected for histopathology evaluation and Immunohistochemical analyses. DMH was efficient to induce malignant lesions. Isolated administration with 5-FU was not effective in decreasing the occurrence of malignant lesions, but the treatment with OncoTherad resulted in a decrease of 20%. Ultimately, the association between immunotherapy and chemotherapy was the most effective, decreasing 60% lesions. In addition, the Onco Therad was able to activate the innate immune system by increasing the signaling pathway to interferon. Thus, immunotherapy with OncoTherad may be one new approach therapeutic for CRC and may act as adjunctive therapy to 5-Fluorouracil chemotherapy.
O presente estudo descreve os efeitos histopatológicos da quimioterapia com 5-Fluorouracil associada à suplementação probiótica no tratamento do câncer colorretal (CCR) induzido quimicamente em ratos, bem como os efeito dessa associação terapêutica na via de sinalização envolvendo PTEN e PI3K. Os resultados demonstraram que a indução do CCR com DMH foi efetiva e levou à ocorrência de lesões neoplásicas como adenocarcinoma e carcinoma in situ em 60% e 40% dos animais do grupo DMH, respectivamente. O tratamento isolado com 5-FU promoveu redução da agressividade das lesões neoplásicas. Interessantemente, o tratamento isolado com probiótico inibiu a progressão tumoral em 40% dos animais. Os outros 60% apresentaram carcinoma in situ e adenocarcinoma. O tratamento combinado com probiótico e 5-FU foi mais efetivo em reduzir a progressão e a agressividade das lesões neoplásicas. Ainda, intensas imunorreatividades para PTEN foram verificadas nos animais que receberam tratamento simultâneo com probiótico e 5-FU em relação aos tratamentos isolados. Em contraste, as imunorreatividades para PI3K foram intensas nos animais do grupo DMH. Considerando os dados em conjunto, a associação entre probiótico e quimioterapia pode constituir uma alternativa terterapêutica promissora para o CCR, uma vez que a resposta antitumoral foi efetiva com essa associação através da modulação da via de sinalização envolvendo PTEN e PI3K.
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