Evaluation of topical n-acetylcysteine in diversion colitis

Abstract

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...

Tissue content of sulfomucins and sialomucins in the colonic mucosa, without fecal stream, undergoing daily intervention with sucralfate

“…However, SCF has antioxidant activity, and the intestinal bypass significantly increases the production of ROS 9,33 . As demonstrated with other substances that possess antioxidant activity (5-ASA, n-acetylcysteine and aqueous extract of Ilex paraguariensis), it is also possible that the SCF has the same antioxidant effects on excluded sigmoid traffic mucosa, preventing epithelial assault, neutrophil infiltration and apoptosis of cells producing mucin 10,11,14 .…”

“…An experimental study showed that it is possible to trigger the onset of epithelial lesions such as those found in the DC by applying enemas with hydrogen peroxide, a potent donor of ROS 15 . The possibility that ROS may trigger the onset of DC gained more support after studies demonstrated that the application of enemas with antioxidants, such as 5-ASA and N-acetylcysteine, to the excluded colon is effective in controlling the disease 11,14,36 .…”

“…Nonose et al score, confirming the results of a previous study 40 . We conducted an intervention for a maximum period of four weeks because this time period was used in most previous studies 10,11,14,15,40 . However, SCF has antioxidant activity, and the intestinal bypass significantly increases the production of ROS 9,33 .…”

“…The application of enemas containing natural or synthetic substances, with antioxidant effects or rich SCFA solutions, improves tissue inflammatory changes detected in the DC model [10][11][12][13][14] . Conversely, the exposure of the colonic mucosa to substances with great oxidant power, such as hydrogen peroxide (H 2 O 2 ), worsens the epithelial damage 15 .…”

Mucin levels in glands of the colonic mucosa of rats with diversion colitis subjected to enemas containing sucralfate and n-acetylcysteine alone or in combination

“…Both substances reduced the levels of oxidative stress in the mucosa of the excluded colon, suppressed the inflammatory process, and promoted epithelial healing 17 - 20 . Despite having a remarkable antioxidant effect, due to its low ability to adhere to the colonic mucosa, NAC requires successive enema applications, which made its use impractical 18 , 19 . In contrast, SCF, in addition to stimulating mucin production by goblet cells, can effectively adhere to the inflamed colonic mucosa 17 , 21 , 22 .…”