RESUMO
It is well documented that nutraceuticals, in general, and Green tea catechins, in particular, possess a potential therapeutic value in inflammatory bowel diseases (IBD) due to their anti-oxidative and anti-inflammatory effects. This study aimed to investigate the possible mechanism of action of catechins in a rat model of colitis induced by 2.4.6 trinitrobenzene sulfonic acid (TNBS). Thirty-five young adult Sprague-Dawley rats were divided into four groups: normal control (n=5), catechins (n=9), TNBS (n=9) and TNBS plus catechins (n=12) treated. Catechin in the form of Epigallocatechin-3-gallate (EGCG) was administered daily by intraperitoneal injection, 1 week before the induction date of UC. Biopsies of the descending colon were collected on days 3, 10 and 17, and partly frozen for molecular studies or fixed for light microscopy. The status of intestinal tissue alterations and mast cells number were also assessed, as well as the mRNA expressions of IL-6, TNF-a and NF-kB, and determination of ROS expression. Histological data depicted a significant amelioration in the TNBS- and EGCG-treated rats compared to the non-treated animals. Catechin expressed strong anti-inflammatory and anti-oxidant effects, ameliorated ulcerative colitis and stabilized mast cells. The mechanism of action occurred basically through the NF-kB pathway and possibly through a crosstalk with other pathways.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Catequina/análogos & derivados , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Chá/química , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Catequina/isolamento & purificação , Catequina/farmacologia , Colite/induzido quimicamente , Colite/imunologia , Colite/patologia , Colo/imunologia , Colo/patologia , Regulação da Expressão Gênica , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/patologia , NF-kappa B/genética , NF-kappa B/imunologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Ácido Trinitrobenzenossulfônico , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
There is now a wealth of experimental evidence indicating that the deficit in endogenous estrogen facilitates the onset of inflammation that can be antagonized by estrogen replacement therapy. This work investigated the role of estrogen in the control of intestinal inflammation in a panel of colitis models, focusing on the morphological changes, the activity of mast cells, the expression of cytokines (IL-1beta, IL-6, and TNF-alpha), fibronectin and reactive oxygen species. Two hundred adult male rats were divided into 4 groups: colitis was induced in Group I and Group II but only the latter was treated with estrogen; Group III received estrogen only, and Group IV saline. Colitis was induced in 4 models using: iodoacetamide; iodoacetamide + enteropathogenic E. coli; 2, 4, 6-Trinitrobenzene sulfonic acid; and dextran sulfate sodium salt. Macroscopic and microscopic evaluations of abdominal structures as well as molecular analysis were made on days 7, 14, 28 and 56. There was a significant improvement in the health condition of the estrogen-treated rats: the inflammation scores were reduced by at least 10-15%, the number of mast cells in the colon decreased by 30%, fibronectin expression was only 50% and reactive oxygen species decreased by 30%. In addition, there was a significant decrease in TNF-alpha, IL-6 and IL-1beta expression by about 25%. In conclusion, there was an improvement in the inflammatory status in all estrogen-treated groups through the duration of the experiment at all-time points. In addition, there was less tissue necrosis as depicted by less fibronectin and a marked antioxidant effect.