Radical induction theory of ulcerative colitis

Pravda, Jay

doi:10.3748/wjg.v11.i16.2371

Cited by 186 publications

(220 citation statements)

References 127 publications

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“…Rupture of this defense system allows the migration of intestinal lumen bacteria into the sterile layers of colon wall. In an attempt to fight against bacterial infiltration, inflammatory cells migrate from the systemic circulation, promoting and keeping the inflammatory system that characterizes the disease 21 . Neutrophil infiltration causes increased production of OFRs, which further aggravates the epithelium harm 20,21 .…”

Section: Discussionmentioning

confidence: 99%

“…The resulting oxidative stress causes histological and biochemical alterations similar to those found in experimental models of chemically induced colitis or human colitis. The oxidative stress causes alterations in the colonic mucosa that aggravate according to the time of diversion [20][21][22][23][24][25][26][27] . Based on these evidences, the use of substances with antioxidant activity was suggested to be effective in the prevention and treatment of this disease 20,27 .The benefits of these substances in the treatment of DC were recently confirmed with the application of enemas with 5-aminosalicylic acid (5-ASA), a powerful antioxidant, was demonstrated to reduce the levels of tissue oxidative stress and improve the inflammatory process in the mucosa without fecal stream, even after the ex-vivo exposure to hydrogen peroxide (H 2 O 2 ) 27 .…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of topical n-acetylcysteine in diversion colitis

Almeida¹,

Pereira²,

Silva³

et al. 2012

J. Coloproctol. (Rio J.)

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Introduction: Diversion colitis (DC) is a benign condition characterized by the appearance of inflammation in the mucosa of the colon or rectum devoid of fecal stream. Oxidative stress has been associated with the etiopathogenesis of the disease. N-acetylcysteine (NAC) is a substance with antioxidant properties, used in different treatments of inflammatory diseases. The purpose of this study was to evaluate the effects of topical applications of NAC in an experimental model of DC. Methods: Thirty-six Wistar rats were submitted to deviation of fecal stream by proximal colostomy and a distal mucosal fistula. They were distributed into 3 experimental groups of 12 animals according to the daily application of enemas containing 0.9% saline or 2 doses of NAC, 25 mg/kg and 100 mg/kg, respectively. In each group, half of the animals were sacrificed after two weeks of irrigation and half after four weeks of irrigation. The diagnosis of colitis was assessed by histopathological analysis and the grade of inflammation by inflammatory grading scale. The results were evaluated with the Mann-Whitney test, adopting significance level of 5% (p<0.05). Results: Daily enema of NAC improved the inflammatory alterations in colon without fecal stream. In colonic segments without fecal stream, the inflammatory score was significantly lower in the animals treated with 100mg/kg, compared with those treated with saline solution or 25 mg/kg of NAC, regardless of the duration of intervention (p<0.05). The inflammatory score in colon segments without fecal stream was significantly lower in the animals treated with both concentration of NAC, compared with those treated with saline, regardless of the concentration and duration of irrigation (p<0.01). Conclusions: Enemas containing NAC improve the inflammatory process and constitute a beneficial tool in the treatment of DC.Keywords: acetylcysteine; colon; colitis; fatty acids, volatile; histology; rats. RESUMO: Introdução:Colite de exclusão (CE) é uma condição benigna caracterizada pelo desenvolvimento de inflamação na mucosa do cólon desprovida de trânsito fecal. O estresse oxidativo tem sido implicado na patogênese da doença. A n-acetilcisteína (NAC) é uma substân-cia com efeitos antioxidantes, sendo utilizada no tratamento de várias doenças inflamatórias. Objetivo: Avaliar os efeitos da aplicação tópica de NAC em modelo de CE. Método: Trinta e seis ratos Wistar foram submetidos ao desvio do trânsito por meio de colostomia proximal e fístula mucosa distal. Os animais foram distribuídos em três grupos experimentais de igual tamanho segundo a aplicação de enemas diários contendo soro fisiológico 0,9% ou NAC nas concentrações de 25 mg/kg ou 100 mg/kg. Em cada grupo, metade dos animais foi sacrificada após duas ou quatro semanas de irrigação. O diagnóstico de CE foi feito por estudo histopatológico e a graduação por escala inflamatória. Na avaliação dos resultados, utilizou-se o teste de Mann-Withney, adotando-se nível de significância de 5% (p<0,05). Resultados: A aplicação intrarretal...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of topical n-acetylcysteine in diversion colitis

Almeida¹,

Pereira²,

Silva³

et al. 2012

J. Coloproctol. (Rio J.)

View full text Add to dashboard Cite

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“…In recent years, the importance of the role of reactive oxygen species (ROS) in the etiopathogenesis of ulcerative colitis and other inflammatory diseases that affect the colon mucosa, such as DC, has increased 13,16,17,18,19 . Likewise, experimental studies have confirmed the role of ROS in the development of chemically induced colitis by acetic acid, TNBS and DSS 20,21,22,23 .…”

Section: Discussionmentioning

confidence: 99%

“…The tissue damage to the colonic mucosa has been attributed to the large capacity of the activated neutrophils to produce ROS 16,19 . Tissue fragments collected from patients with ulcerative colitis showed greater activity in lipid peroxidation levels compared to normal tissue 31 .…”

Section: Discussionmentioning

confidence: 99%

Reduction in oxidative stress levels in the colonic mucosa without fecal stream after the application of enemas containing aqueous Ilex paraguariensis extract

Cunha¹,

Silva

Almeida

et al. 2011

Acta Cir. Bras.

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PURPOSE: To evaluate the antioxidant effects of enemas containing aqueous extract of Ilex paraguariensis, comparing segments with and without fecal stream and correlating the segments with the duration of intervention. METHODS: Twenty-six Wistar rats were subjected to a diversion of the fecal stream in the left colon by a proximal colostomy and distal mucosal fistula. The rats were distributed randomly into two experimental groups of 13 animals each based on the time of sacrifice after surgical procedure (two or four weeks). Each group was then divided into two experimental subgroups that received either second daily enemas containing 0.9% saline solution or aqueous extract of Ilex paraguariensis at 0.2g/100g. Colitis was diagnosed by histopathological analysis and the detection of oxidative tissue damage by measuring the levels of malondialdehyde. The Mann-Whitney test was used to compare the tissue levels of malondialdehyde between colon segments with and without fecal stream in each experimental group, and the Kruskal-Wallis test was used to verify the variance between the levels of oxidative stress according the duration of the irrigation; both tests determined significance at 5% (p<0.05). RESULTS: The levels of malondialdehyde in the animals subjected to intervention in the colon with saline with and without fecal stream after two and four weeks of irrigation were 0.05±0.006 and 0.06±0.006, and 0.05± 0.03 and 0.08 ±0.02, respectively. The malondialdehyde levels in the animals irrigated with Ilex paraguariensis with and without fecal stream after two and four weeks of irrigation were 0.010±0.002 and 0.02±0.004, and 0.03±0.007 and 0.04±0.01, respectively. After two and four weeks of intervention, the levels of malondialdehyde were lower in the animals irrigated with Ilex paraguariensis regardless of the time of irrigation (p=0.0001 and p=0.002, respectively). CONCLUSION: The daily rectal application of enemas containing aqueous extract of Ilex paraguariensis decreases oxidative tissue damage in the colon without fecal stream regardless of the time of irrigation.

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“…The immune barrier and physical barrier are made up of the immune cells, and epithelial cells and tight junction (TJ) complex, respectively [5]. It was reported that disturbance of the intestinal mucosal immune system of fish results in an impaired immune response leading to pathogen translocation, infection and inflammatory bowel diseases [5,6]. Therefore, maintaining the intestinal mucosal immune barrier function is of utmost importance for fish [5].…”

Section: Introductionmentioning

confidence: 99%