Prophylactic role of curcumin in dextran sulfate sodium (DSS)-induced ulcerative colitis murine model

Arafa, Hossam M.M.; Hemeida, Ramadan A.M.; El-Bahrawy, Ali H.; Hamada, Farid M.A.

doi:10.1016/j.fct.2009.03.003

Cited by 107 publications

(67 citation statements)

References 47 publications

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“…Studies conducted in experimental models of chemically induced colitis confirmed the beneficial effects of antioxidants, improving the inflammatory process of colonic mucosa [27][28][29][30][31] . Several drugs have been tested with effective results in experimental conditions, including 5-ASA, glucocorticoids, L-carnitine, L-glutamine, melatonin and antioxidants found in the aqueous extract of Ilex paraguariensis and Curcuma longa [33][34][35][36][37][38][39] . Unfortunately, although they are effective in the treatment of this disease, some of these substances cause side effects when used at higher doses and for longer periods 27,36 .…”

Section: Discussionmentioning

confidence: 99%

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%

Evaluation of topical n-acetylcysteine in diversion colitis

Almeida¹,

Pereira²,

Silva³

et al. 2012

J. Coloproctol. (Rio J.)

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“…Cells have developed defense mechanisms to maintain the balance between ROS production and neutralization and avoid oxidative stress 12,[25][26][27] . The colon mucosa is particularly vulnerable to oxidative stress 23 .…”

Section: Discussionmentioning

confidence: 99%

“…In plants, they protect against insects and microorganisms and are responsible for pigmentation and some organoleptic characteristics of food 8 . Recently, natural polyphenolic substances such as curcumin (extract from Curcuma longa) and revesterol (extract from grapes) are being increasingly used as antioxidant substances in different experimental models of colitis 9,10,11,12 . Although it has been demonstrated experimentally that the pathogenesis of diversion colitis (DC) is related to oxidative stress due to changes in the supply of short-chain fatty acids (SCFA) to the excluded colon, to the best of our knowledge, the antioxidant effects of natural polyphenols in the aqueous extract and fed a standard rodent chow diet.…”

Section: Introductionmentioning

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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“…• Prevented the injurious effects of DSS and ameliorated release of TNF-a and NO in a rat model (Arafa et al, 2009). …”

Section: Figurementioning

confidence: 99%

Curcumin: an orally bioavailable blocker of TNF and other pro‐inflammatory biomarkers

Aggarwal

Gupta

Sung

2013

British J Pharmacology

343

239

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TNFs are major mediators of inflammation and inflammation-related diseases, hence, the United States Food and Drug Administration (FDA) has approved the use of blockers of the cytokine, TNF-a, for the treatment of osteoarthritis, inflammatory bowel disease, psoriasis and ankylosis. These drugs include the chimeric TNF antibody (infliximab), humanized TNF-a antibody (Humira) and soluble TNF receptor-II (Enbrel) and are associated with a total cumulative market value of more than $20 billion a year. As well as being expensive ($15 000-20 000 per person per year), these drugs have to be injected and have enough adverse effects to be given a black label warning by the FDA. In the current report, we describe an alternative, curcumin (diferuloylmethane), a component of turmeric (Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-a action and production in in vitro models, in animal models and in humans. In addition, we provide evidence for curcumin's activities against all of the diseases for which TNF blockers are currently being used. Mechanisms by which curcumin inhibits the production and the cell signalling pathways activated by this cytokine are also discussed. With health-care costs and safety being major issues today, this golden spice may help provide the solution. LINKED ARTICLESThis article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx

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Prophylactic role of curcumin in dextran sulfate sodium (DSS)-induced ulcerative colitis murine model

Cited by 107 publications

References 47 publications

Evaluation of topical n-acetylcysteine in diversion colitis

Evaluation of topical n-acetylcysteine in diversion colitis

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

Curcumin: an orally bioavailable blocker of TNF and other pro‐inflammatory biomarkers

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