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Chronic inflammatory bowel disease is characterised by an up-regulation of the synthesis and release of a variety of pro-inflammatory mediators leading to excessive tissue injury. Flavonoids are able to inhibit enzymes and/or due to their antioxidant properties regulate the immune response. The goal of the present study was to evaluate the mechanisms of action of phenolic compounds present in grape juice on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. A total of forty-one male Wistar rats were randomised into seven groups: negative control group; TNBS non-treated induced colitis; 2 % grape juice control group; 1 % grape juice 24 h after TNBS colitis induction; 1 % grape juice on day 7 after colitis induction; 2 % grape juice 24 h after colitis induction; 2 % grape juice on day 7 after colitis induction. The 1 % grape juice-treated induced colitis group showed marked clinical improvement when compared with the TNBS-induced colitis group. Rats that received 1 % grape juice, on day 7 after colitis induction, presented reduced intensity of macroscopic and histological scores. Statistically significant differences (P,0·05) of TNF-a and inducible NO synthase mRNA expression were detected in the groups treated with grape juice at the 1 % dose after inducing experimental colitis when compared with the TNBS group. Grape juice reduced the noxious effects induced by colitis caused by TNBS, especially at the 1 % dose.

Ulcerative colitis (UC) is a disease of the colon and rectum characterized by a nonspecific chronic inflammation mediated by the concerted response of cellular and humoral events. Prostaglandins are synthesized by cyclooxygenase (COX)-1 and -2 and exhibit both pro-and anti-inflammatory activity. To evaluate COX-1 and COX-2 immunoexpression in 42 cases of UC and to correlate it with clinicopathological parameters, COX-1 and COX-2 expression was investigated by the immunohistochemistry method. Only patients with all pertinent clinical and evolutive data as well as with adequate biopsy material were included in the study. Fifteen samples of colorectal adenocarcinoma and 14 of large bowel with no histological changes were used for positive and negative controls, respectively. UC patients showed COX-1 immunoreactivity in epithelial cells in 29% of the cases and in inflammatory cells in 43%. COX-2 positivity in epithelial and inflammatory cells was found in 69% of the samples. The comparison between UC and the control groups revealed that the UC group had significantly more positive cases for COX

No abstract

Crohn's disease (CD) is associated with gut barrier dysfunction. Besides the baseline barrier defect, a subgroup of patients also expresses an intestinal barrier hyperresponsiveness to nonsteroidal anti-inflammatory drugs. On the other hand, the anti-tumour necrosis factor alpha (TNF-α) treatment has brought benefits to these patients. Thus, this study aimed to evaluate the effect of lumiracoxib, a selective-cyclooxygenase-2 (COX-2) inhibitor, and Etanercept (ETC), a TNF-α antagonist on the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. A total of 47 Wistar rats were randomized into seven groups, as follows: (1) Sham: sham induced-colitis; (2) TNBS: nontreated induced-colitis; (3) Lumiracoxib control; (4) Lumiracoxib-treated induced-colitis; (5) ETC control; (6) ETC-treated induced-colitis; (7) Lumiracoxib-ETC-treated induced-colitis. Rats from groups 6 and 7 presented significant improvement of macroscopic and histopathological damages in the distal colon. The gene expression of COX-2 mRNA, as well of TNF-α mRNA, decreased significantly in groups 6 and 7 compared to the TNBS nontreated and lumiracoxib-treated groups. The treatment only with lumiracoxib did not reduce the inflammation on TNBS-induced experimental colitis. ETC attenuated the damage seen in the colon and reduced the inflammation caused by TNBS. Our results suggest that down-regulation of TNF-α and COX-2 resulted in a decrease in inflammation caused by TNBS and thus provided some protection from the colonic damage caused by TNBS.

Melatonin has been described as a protective agent against cell death and oxidative stress in different tissues, including in the reproductive system. However, the information on the action of this hormone in rat uterine apoptosis is low. Our objective was to evaluate the effects of melatonin on mechanisms of cell death in uterus of rats exposed to continuous light stress. Twenty adult Wistar rats were divided into two groups: GContr (vehicle control) and GExp which were treated with melatonin (0.4 mg/mL), both were exposed to continuous light for 90 days. The uterus was removed and processed for quantitative real time PCR (qRT-PCR), using PCR-array plates of the apoptosis pathway; for immunohistochemistry and TUNEL. The results of qRT-PCR of GEXP group showed up-regulation of 13 and 7, pro-apoptotic and anti-apoptotic genes, respectively, compared to GContr group. No difference in pro-apoptotic proteins (Bax, Fas and Faslg) expression was observed by immunohistochemistry, although the number of TUNEL-positive cells was lower in the group treated with melatonin compared to the group not treated with this hormone. Our data suggest that melatonin influences the mechanism and decreases the apoptosis in uterus of rats exposed to continuous light.

The aim of this study was to evaluate the effects of grape juice on colon carcinogenesis induced by azoxymethane (AOM) and expression of NF-kB, iNOS and TNF-α. Methods: Forty male Wistar rats were divided into 7 groups: G1, control; G2, 15 mg/kg AOM; G3, 1% grape juice 2 weeks before AOM; G4, 2% grape juice 2 weeks before AOM; G5, 1% grape juice 4 weeks after AOM; G6, 2% grape juice 4 weeks after AOM; G7, 2% grape juice without AOM. Histological changes and aberrant crypt foci (ACF) were studied, while RNA expression of NFkB, TNF-and iNOS was evaluated by qPCR. Results: The number of ACF was higher in G2, and G4 presented a smaller number of crypts per focus than G5 (p=0.009) and G6. Small ACF (1-3) were more frequent in G4 compared to G2, G5 and G6 (p=0.009, p=0.009 and p=0.041, respectively). RNA expression of NF-kB was lower in G3 and G4 compared to G2 (p=0.004 and p=0.002, respectively). A positive correlation was observed between TNF-α and NF-kB gene expression (p=0.002). In conclusion, the administration of 2% grape juice before AOM reduced the crypt multiplicity, attenuating carcinogenesis. Lower expression of NF-kB was observed in animals exposed to grape juice for a longer period of time, regardless of concentration.

Crohn's disease (CD) is associated with gut barrier dysfunction. Tumour necrosis factor-α (TNF-α) plays an important role into the pathogenesis of several inflammatory diseases because its expression is increased in inflamed mucosa of CD patients. Anti-TNF therapy improves significantly mucosal inflammation. Thus, this study aimed to evaluate the effect of Etanercept (ETC), a tumour necrosis factor alpha (TNF-α) antagonist on the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. A total of 18 Wistar rats were randomized into four groups, as follows: (1) Sham: sham induced-colitis; (2) TNBS: non-treated induced-colitis; (3) ETC control; (4) ETC-treated induced-colitis. Rats from group 4 presented significant improvement either of macroscopic or of histopathological damage in the distal colon. The gene expression of TNF-α mRNA, decreased significantly in this group compared to the TNBS non-treated group. The treatment with etanercept attenuated the colonic damages and reduced the inflammation caused by TNBS. Taken together, our results suggest that ETC attenuates intestinal colitis induced by TNBS in Wistar rats by TNF-α downregulation.