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Introduction. Anti-inflammatories, immunosuppressants, and immunobiological are commonly used in the treatment of inflammatory bowel disease. However, some patients do not present an adequate response or lose effective response during the treatment. A recent study found a potential anti-inflammatory effect of the hydroalcoholic extract of Mimosa caesalpiniifolia on trinitrobenzene sulfonic acid-induced colitis in Wistar rats.Objective. To evaluate the effects of M. caesalpiniifolia pre-formulation on the intestinal barrier using dextran sulfate sodium-induced colitis model.Materials and methods. Leaf extracts were prepared in 70% ethanol and dried with a Buchi B19 Mini-spray dryer using 20% Aerosil® solution. Thirty-two male Wistar rats were randomized into four groups: basal control, untreated colitis, pre-formulation control (125 mg/kg/day), and colitis treated with pre-formulation (125 mg/kg/day). Clinical activity index was recorded daily and all rats were euthanized on the ninth day. Colon fragments were fixed and processed for histological and ultrastructural analyses.Stool samples were collected and processed for analysis of the short-chain fatty acid.Results. Treatment with the pre-formulation decreased the clinical activity (bloody diarrhea), inflammatory infiltrate, and the ulcers. Pre-formulation did not repair the epithelial barrier and there were no significant differences in the goblet cells index. There was a significant difference in butyrate levels in the rats treated with the pre-formulation.Conclusions. The pre-formulation minimized the clinical symptoms of colitis and intestinal inflammation, but did not minimize damage to the intestinal barrier.
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BACKGROUND: Colorectal cancer is the third cause of cancer worldwide and a quarter of them are in the rectum. DEK oncogene is involved in several nuclear processes and can accelerate tumorigenesis. OBJECTIVE: This study aims to evaluate the immunoexpression of DEK and Phospho-P38 proteins before neoadjuvant therapy in patients with rectum adenocarcinoma and correlate it with a clinical response and survival. METHODS: Patients with adenocarcinoma of the middle and low rectum who underwent chemotherapy and radiotherapy followed by surgical tumor resection were included. The expression and quantification were studied by immunohistochemistry in the tumor biopsy tissues using a HScore system. Score ≥4 were considered positive and those with <4 negative. RESULTS: 22 patients were included with a mean age of 63.55 years (SD: ±13.49). The clinical-stage before treatment was T3 on 72.7%, T4 on 18.2%, 31.8% were N1, 50% N0 and all M0. After chemo and radiotherapy, 54.6% were T3; 22.7% were classified as T2; 9.1% as T1, and 13.6% were T0. Among the tumors, 22.7% were positive for DEK and 63.6% positive for Phospho-P38. There was a positive correlation between DEK protein before treatment and pTNM stage (P=0.011). Phospho-P38 protein showed no correlation with these parameters. Patients with a negative HScore had a mean survival of 141.33 months (95%CI: 112.41-170.25) and those with a positive HSscore had a mean survival of 25.10 months (95%CI: 17.36-32.84; P<0.001). CONCLUSION: A higher expression of DEK was observed in advanced stages. Patients who presented DEK expression <4 had a higher survival, being a factor of worst prognosis.
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Adenocarcinoma , Neoplasias Retais , Proteínas Cromossômicas não Histona/metabolismo , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Oncogênicas/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose , Prognóstico , Neoplasias Retais/patologia , Neoplasias Retais/terapiaRESUMO
ABSTRACT Background: Colorectal cancer is the third cause of cancer worldwide and a quarter of them are in the rectum. DEK oncogene is involved in several nuclear processes and can accelerate tumorigenesis. Objective: This study aims to evaluate the immunoexpression of DEK and Phospho-P38 proteins before neoadjuvant therapy in patients with rectum adenocarcinoma and correlate it with a clinical response and survival. Methods: Patients with adenocarcinoma of the middle and low rectum who underwent chemotherapy and radiotherapy followed by surgical tumor resection were included. The expression and quantification were studied by immunohistochemistry in the tumor biopsy tissues using a HScore system. Score ≥4 were considered positive and those with <4 negative. Results: 22 patients were included with a mean age of 63.55 years (SD: ±13.49). The clinical-stage before treatment was T3 on 72.7%, T4 on 18.2%, 31.8% were N1, 50% N0 and all M0. After chemo and radiotherapy, 54.6% were T3; 22.7% were classified as T2; 9.1% as T1, and 13.6% were T0. Among the tumors, 22.7% were positive for DEK and 63.6% positive for Phospho-P38. There was a positive correlation between DEK protein before treatment and pTNM stage (P=0.011). Phospho-P38 protein showed no correlation with these parameters. Patients with a negative HScore had a mean survival of 141.33 months (95%CI: 112.41-170.25) and those with a positive HSscore had a mean survival of 25.10 months (95%CI: 17.36-32.84; P<0.001). Conclusion: A higher expression of DEK was observed in advanced stages. Patients who presented DEK expression <4 had a higher survival, being a factor of worst prognosis.
RESUMO Contexto: O câncer colorretal é mundialmente, a terceira causa de câncer e um quarto destes estão localizados no reto. O oncogene DEK está envolvido em vários processos nucleares e pode acelerar a tumorigênese. Objetivo: Este estudo tem como objetivo avaliar a imunoexpressão das proteínas DEK e Fosfo-P38 antes da terapia neoadjuvante em pacientes com adenocarcinoma de reto e correlacioná-la com resposta clínica e sobrevida. Métodos: Foram incluídos pacientes com adenocarcinoma de reto médio e baixo submetidos à quimio e radioterapia seguida de ressecção cirúrgica do tumor. A expressão e quantificação foram estudadas por imuno-histoquímica nos tecidos de biópsia tumoral utilizando um sistema HScore. Escores ≥4 foram considerados positivos e aqueles com <4 negativos. Resultados: Foram incluídos 22 pacientes com média de idade de 63,55 anos (DP: ±13,49). O estágio clínico antes do tratamento era T3 em 72,7%, T4 em 18,2%, 31,8% eram N1, 50% N0 e todos M0. Após a quimio e radioterapia, 54,6% eram T3; 22,7% eram T2; 9,1% eram T1 e 13,6% T0. Entre os tumores, 22,7% foram positivos para DEK e 63,6% positivos para Phospho-P38. Houve uma correlação positiva para a imunoexpressão da proteína DEK e o estágio pTNM (P=0,011). A proteína fosfo-P38 não apresentou correlação com esses parâmetros. Pacientes com HScore negativo para DEK tiveram sobrevida média de 141,33 meses (IC95%: 112,41-170,25) e aqueles com HScore positivo tiveram sobrevida média de 25,10 meses (IC95%: 17,36-32,84) (P<0,001). Conclusão: Observou-se maior expressão de DEK em estágios avançados. Os pacientes que apresentaram expressão de DEK <4 tiveram maior sobrevida, sendo um fator de pior prognóstico.
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BACKGROUND AND AIM: Human gut microbiota play an important role in metabolism and host physiology. Perturbations of the gut microbial communities lead to the development of various diseases such as inflammatory bowel disease, celiac disease, allergic diseases, and metabolic diseases. Crohn's disease is a chronic inflammatory bowel disease characterized by periods of remission and relapse. Several studies suggest that intestinal inflammation arises due to an abnormal response of the intestinal immune system to the fecal microbiota. The goal of the study was to evaluate the relative amount of four bacterial groups in fecal samples of Crohn's disease patients and their relation to the inflammatory activity. METHODS: We studied stool samples of 105 individuals, 54 with Crohn's disease and 51 as a control group. The DNA extracted from the stool samples was subjected to real-time polymerase chain reaction (qPCR) for quantification of the Bacteroidetes phylum, class Bacilli, and Bifidobacteriaceae and Enterobacteriaceae families. RESULTS: We found a significant increase in Bacteroidetes in Crohn's disease samples when compared to the control group (14 650 and 2060 CFU/ng DNA, respectively) (P = 0.014). On the other hand, we observed a significant reduction in Bacilli and Bifidobacteriaceae (13 and 58 CFU/ng DNA, respectively) (P < 0.0001). In contrast, patients without any drug treatment presented an increase of Bacilli and Bifidobacteriaceae (102 521 and 6235 CFU/ng DNA, respectively) (P < 0.0001). CONCLUSION: The commensal bacteria were decreased in fecal samples of participants with Crohn's disease when compared to the control group. There was no relation between the disease location and/or disease activity with the microbiota.
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OBJECTIVES: The aim of this study was to evaluate the preventive effects of extra virgin olive oil (EVOO) or flaxseed oil (FO) on dextran sodium sulfate (DSS)-induced acute ulcerative colitis in female mice. METHODS: Eighty C57BL/6J mice of 8-weeks-old were divided in four groups: Control (SO), 10%EVOO, 10%FO and 5%EVOO+5%FO. The oils were given through the AIN-93M diet. After 30 days, animals were divided in four more groups, in which half received 3%DSS in water for 5 days. Body weight loss, bleeding and stool consistency were verified for the Disease Activity Index (DAI). Animals were euthanized and their colon and spleen weighted and measured. Histopathological analysis, the concentrations of TNF-α, IL-1ß, and IL-10 and the iNOS expression were evaluated in the colon samples. RESULTS: Animals that received DSS presented with elevated disease activity index values; increased colon weight-to-length ratio; augmented leukocyte infiltration into the lamina propria and submucosa; and increased production of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6, and greater inducible nitric oxide synthase expression in the distal colon. Individually or in combination, the oils were not able to reverse or mitigate any of the DSS-induced symptoms or damage. Additionally, the group of animals treated with DSS and supplemented with FO displayed increased spleen weight-to-body weight ratio, and the group that received a combination of EVOO and FO presented increased TNF-α levels compared with the respective control group. CONCLUSION: Consumption of large amounts of EVOO and FO as a treatment for or prevention against ulcerative colitis could potentially elicit unwanted adverse effects.
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Colite Ulcerativa , Colite , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/prevenção & controle , Colo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Feminino , Óleo de Semente do Linho , Camundongos , Camundongos Endogâmicos C57BL , Azeite de OlivaRESUMO
The aim of this study was to evaluate the preventive and/or protective action of Mimosa caesalpiniifolia (M. caesalpiniifolia) following experimental colitis in rats. The rats were randomized into ten groups (n=10 per group), as follows: G1 - Sham group:; G2 - TNBS group; G3, G4 -colitis and treated with hydroalcoholic extract of M. caesalpiniifolia 250 mg/kg/day after and before/after inducing colitis, respectively; G5, G6 - colitis and treated with hydroalcoholic extract of M. caesalpiniifolia at 125 mg/kg/day after and before/after inducing colitis respectively; G7,G8 - colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively; G9,G10 - colitis and treated with ethylacetate fraction of M. caesalpiniifolia at 50 mg/kg/day after and before/after inducing colitis, respectively. Rats treated with hydroalcoholic extract of M. caesalpiniifolia for both doses showed lower tissue damage in the distal colon. Ethylacetate fraction was effective at the highest dose only when administrated after inducing colitis. A downregulation of COX-2 was detected to rats suffering colitis and treated with M. caesalpiniifolia at high dose. On the other hand, TNF-alpha immunoexpression decreased in groups treated with M. caesalpiniifolia at low dose after inducing colitis. In summary, our results suggest that M. caesalpiniifolia attenuated the lesions of the colon, reduced inflammation, and modulates the expression of COX-2 and TNF-α during chronic colitis induced by TNBS when using for therapeutic purposes on a dose-dependent manner.
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Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Ciclo-Oxigenase 2/metabolismo , Mimosa/química , Extratos Vegetais/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Modelos Animais de Doenças , Masculino , Ratos , Ratos WistarRESUMO
The objective of this study was to evaluate the action of soy isoflavones and 17 beta estradiol on the extracellular matrix in the uterus and mammary gland of diabetic rats. Sixty adult female rats underwent ovariectomy, then randomized into seven groups of ten animals each: Non-diabetic: GI Sham control animals ovariectomized; and GII control ovariectomized that received propylene glycol vehicle. Diabetic: GIII Sham control diabetic animals ovariectomized; GIV ovariectomized diabetic animals receiving propylene glycol vehicle; GV diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage); GVI ovariectomized diabetic rats treated with estrogen (17b-estradiol, 10 mg/kg, subcutaneously); GVII diabetic ovariectomized animals treated with soy isoflavones (150 mg/kg by gavage), and with estrogen (17b-estradiol, 10 mg/kg combination therapy). Treatments occurred during 30 consecutive days. After animals euthanasia, a portion of the uterus was immersed in liquid nitrogen for molecular biology analysis, the other portion of uterus and mammary glands were removed and processed for paraffin embedding. Soy isoflavones (GV) and 17b estradiol improved the production of compounds of extracellular matrix, such as small leucine-rich proteoglycans (SLRPs). The combination of both therapies had an additive effect in SLRPs expression. Soy isoflavones contribute to the uterine integrity of SLRPs of diabetic rats.
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Diabetes Mellitus Experimental/tratamento farmacológico , Estradiol/farmacologia , Isoflavonas/farmacologia , Glândulas Mamárias Animais/efeitos dos fármacos , Extratos Vegetais/farmacologia , Útero/efeitos dos fármacos , Animais , Glicemia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Estradiol/uso terapêutico , Feminino , Resistência à Insulina , Isoflavonas/uso terapêutico , Glândulas Mamárias Animais/patologia , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Ratos , Útero/patologiaRESUMO
Colorectal cancer is the third most common cancer worldwide in both sexes, with similar geographic patterns between genders. This neoplasm has good prognosis if the disease is diagnosed at early stages. The aim of this study was to evaluate the effect of red grape juice on the expression of COX-2 and Ki-67 expression following colon carcinogenesis induced by azoxymethane (AOM). Thirty-five rats were randomly distributed into seven groups (n=5 per group): G1: SHAM or negative control received only saline; G2 (positive control): animals received 15 mg/kg AOM; G3: animals received 1% red grape juice 2 weeks before the administration of AOM; G4: animals received 2% red grape juice 2 weeks before the administration of AOM; G5: animals received 1% red grape juice 4 weeks after the last administration of AOM; G6: animals received 2% red grape juice 4 weeks after the last administration of AOM; G7: animals received only 2% red grape juice. COX-2 mRNA expression was reduced in animals treated with 1% red grape juice before AOM induction or 2% red grape juice after AOM induction. COX-2 immunoexpression was also reduced to groups treated with red grape juice at 1% before and after AOM induction or 2% red grape juice after AOM induction. Decreased immunoexpression of Ki-67 positive cells was observed in animals treated with 1% grape juice before AOM-treated animals. Taken together, grape juice concentrate is able to exert some chemopreventive activity on rat colon carcinogenesis.
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Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/prevenção & controle , Extratos Vegetais/administração & dosagem , Vitis/química , Animais , Azoximetano , Neoplasias do Colo/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Sucos de Frutas e Vegetais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
UNLABELLED: 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 NF- kB, 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.
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Focos de Criptas Aberrantes/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Ciclo-Oxigenase 2/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , NF-kappa B/genética , Fator de Necrose Tumoral alfa/genética , Vitis/química , Focos de Criptas Aberrantes/induzido quimicamente , Focos de Criptas Aberrantes/genética , Focos de Criptas Aberrantes/patologia , Animais , Apoptose/efeitos dos fármacos , Azoximetano/toxicidade , Carcinógenos/toxicidade , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Masculino , Fitoterapia , Extratos Vegetais , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/tratamento farmacológico , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , RNA Mensageiro/genética , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais CultivadasRESUMO
OBJECTIVES: The aim of this study was to evaluate if grape juice concentrate is able to protect against experimental colon carcinogenesis. MATERIAL AND METHODS: For this purpose, a total of 35 male Wistar rats were randomly distributed into seven groups: G1: SHAM animals receiving only saline; G2: animals receiving 15 mg/kg azoxymethane (AOM); G3: animals receiving 1% grape juice concentrate 2 weeks before the administration of AOM; G4: animals receiving 2% grape juice concentrate 2 weeks before the administration of AOM; G5: animals receiving 1% grape juice concentrate 4 weeks after the last administration of AOM; G6: animals receiving 2% grape juice concentrate 4 weeks after the last administration of AOM; G7: animals receiving only 2% grape juice concentrate. RESULTS: The group that received 2% grape juice concentrate before induction with AOM showed the decreased expression of Bcl-2 compared to those animals that were induced by AOM (positive control). Regarding Bax, animals that received grape juice at 2% decreased Bax immunoexpression when compared to AOM group. Furthermore, animals that intake grape juice at 1% after induced by AOM decreased Bax immunoexpression as well. 8-OHdGLI did not show significant statistically differences (p > 0.05) among groups. CONCLUSION: In summary, our results demonstrate that grape juice is able to modulate rat colon carcinogenesis as a result of induction of apoptosis.
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Anticarcinógenos/farmacologia , Apoptose/efeitos dos fármacos , Azoximetano , Colo/efeitos dos fármacos , Neoplasias do Colo/prevenção & controle , Sucos de Frutas e Vegetais , Estresse Oxidativo/efeitos dos fármacos , Vitis , 8-Hidroxi-2'-Desoxiguanosina , Animais , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Modelos Animais de Doenças , Frutas , Masculino , Fitoterapia , Plantas Medicinais , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Wistar , Fatores de Tempo , Proteína X Associada a bcl-2/metabolismoRESUMO
Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. Flavonoids exert several biological activities, which are mainly related to their ability to inhibit inflammatory process and/or to their antioxidant properties, and are able to regulate the immune response. The aim of this study was to evaluate whether phenolic compounds present in grape juice could reduce the inflammatory effects induced by experimental colitis. A total of 41 male Wistar rats were randomized into seven groups, as follows: G1--Sham group: sham induced-colitis rats; G2--(2,4,6-rinitrobenzenesulfonic acid) TNBS group: nontreated induced-colitis; G3--2% grape juice control group; G4--1% grape juice 24h after TNBS colitis induction; G5--1% grape juice on day 7 after colitis induction; G6--2% grape juice 24h after colitis induction; G7--2% grape juice on day 7 after colitis induction. Genotoxicity was evaluated by comet assay. Immunohistochemistry was determined using the streptavidin-biotin-peroxidase method being analyzed in control (normal tissue) and "hot spot" areas i.e., presenting inflammatory process being graded as 1 (weak), 2 (moderate), or 3 (strong). Both parameters were evaluated in the cytoplasm of epithelial or inflammatory cells. TNF-immunoexpression and iNOS were reduced after drinking grape juice 24 h or after 7 days for all doses tested. COX-2 was reduced in the groups exposed to 1% grape juice 24 h or 7 days of exposure. The grape juice at 1% dose in the last 7 days of treatment as well as grape juice at 2% dose decreased the peripheral blood genotoxicity. Taken together, the grape juice mainly at 1% dose exerts anti-inflammatory effects in chronic colitis caused by TNBS as a result of down regulation in the expression of pro-inflammatory cytokines and reduction of genotoxicity in peripheral blood cells.
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Anti-Inflamatórios/uso terapêutico , Bebidas , Colite/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Vitis , Animais , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/imunologia , Colite/patologia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/patologia , Ensaio Cometa , Ciclo-Oxigenase 2/imunologia , Dano ao DNA/efeitos dos fármacos , Frutas , Masculino , Óxido Nítrico Sintase Tipo II/imunologia , Fitoterapia , Extratos Vegetais/farmacologia , Ratos Wistar , Ácido Trinitrobenzenossulfônico , Fator de Necrose Tumoral alfa/imunologiaRESUMO
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.
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Bebidas/análise , Colite/induzido quimicamente , Colite/tratamento farmacológico , Fenóis/farmacologia , Ácido Trinitrobenzenossulfônico/toxicidade , Vitis/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Colite/patologia , Colo/patologia , Relação Dose-Resposta a Droga , Masculino , Fenóis/química , Distribuição Aleatória , Ratos , Ratos WistarRESUMO
The nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used in the management of pain and inflammation. Unfortunately, they are associated with dose-dependent gastrointestinal (GI) adverse events ranging from dyspepsia to symptomatic and complicated ulcers. The mechanism of NSAID action is attributed to the cyclooxygenase (COX) inhibition. New anti-inflammatory drugs have been synthesized, such as selective COX-2 inhibitors, however, these drugs may present side effects, such as modification of the epithelial barrier. Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. A possible association between the use of NSAIDs and the relapse of IBD has been repeatedly suggested. For this reason, many studies are conducted with the use of COX-2 in experimental models. The objective of this review is to describe the role of NSAIDs and COX-2 inhibitors in different experimental models of colitis. We reviewed controlled trials, original articles, case reports and reviews. The role of selective inhibition of COX-2 in the inflammatory process and the course of experimental and human colitis is controversially discussed. In conclusion, the relative role of COX-2 selective inhibitors on human and experimental colitis remains to be explored. Thus, the use of COX-2 inhibitors in IBD should be considered with caution.
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Anti-Inflamatórios não Esteroides/farmacologia , Colite/induzido quimicamente , Inibidores de Ciclo-Oxigenase 2/farmacologia , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Doença Crônica , Ensaios Clínicos como Assunto , Colite/enzimologia , Colite/patologia , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Humanos , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Prostaglandinas/fisiologiaRESUMO
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.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Diclofenaco/análogos & derivados , Imunoglobulina G/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Receptores do Fator de Necrose Tumoral/administração & dosagem , Animais , Colite/induzido quimicamente , Colite/imunologia , Colite/metabolismo , Colo/imunologia , Colo/patologia , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Diclofenaco/administração & dosagem , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Quimioterapia Combinada , Etanercepte , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Ácido Trinitrobenzenossulfônico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologiaRESUMO
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.
Assuntos
Colite/tratamento farmacológico , Colite/metabolismo , Imunoglobulina G/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Colite/induzido quimicamente , Colo/efeitos dos fármacos , Colo/patologia , Etanercepte , Regulação da Expressão Gênica/efeitos dos fármacos , Imunoglobulina G/farmacologia , Imuno-Histoquímica , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Coloração e Rotulagem , Ácido TrinitrobenzenossulfônicoRESUMO
Inflammatory bowel disease (IBD) is a common chronic gastrointestinal disorder characterized by alternating periods of remission and active intestinal inflammation. Some studies suggest that antiinflammatory drugs are a promising alternative for treatment of the disease. Thus, this study aimed to evaluate the effect of lumiracoxib, a selective-cyclooxygenase-2 (COX-2) inhibitor, on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis. Wistar rats (n = 25) were randomized into four groups, as follows: Group (1) Sham group: sham induced-colitis rats; Group (2) TNBS group: nontreated induced-colitis rats; Group (3) Lumiracoxib control group; and Group (4) Lumiracoxib-treated induced-colitis rats. Our results showed that rats from groups 2 and 4 presented similar histopathological damage and macroscopic injury in the distal colon as depicted by significant statistically differences (P < 0.01; P < 0.05) compared to the other two groups. Weak expression of COX-2 mRNA was detected in normal colon cells, while higher levels of COX-2 mRNA were detected in group 2 and group 4. Therapy with lumiracoxib reduced COX-2 expression by 20-30%, but it was still higher and statistically significant compared to data obtained from the lumiracoxib control group. Treatment with the selective COX-2 inhibitor lumiracoxib did not reduce inflammation-associated colonic injury in TNBS-induced experimental colitis. Thus, the use of COX-2 inhibitors for treating IBD should be considered with caution and warrants further experimental investigation to elucidate their applicability.