The effect of progesterone in the prevention of the chemically induced experimental colitis in rats

Abstract

PURPOSE:To study the effects of progesterone on an experimental colitis model. METHODS:Wistar albino rats were treated subcutaneously with 2mg/kg once a day during seven days Colitis was induced by intrarectal administration of 5mg trinitrobenzene sulfonic acid (TNBS). Disease activities, macroscopic and microscopic scores were evaluated.To determine the response provoked by progesterone we measured Colonic malondialdehyde (MDA), TNF alfa, IL-6 and Nitric oxide (NO) levels in addition to the MPO (Myeloperoxidase) and caspase-3 activities. RESULTS:Progesterone ameliorated significantly the macroscopic and microscopic scores. TNBS-induced colitis significantly increased the colonic MDA levels and caspase-3 activities in group 2 in comparison to the control group. The results of the study revealed a decline in MDA, NO, IL6 and TNF-α levels in the colon tissue and in blood due to progesterone therapy in group 3 when compared to the group 2, a significant improvement. Progesterone treatment was associated with decreased MDA, MPO, TNF alfa and caspase-3 activity. CONCLUSION:Progesterone therapy decreased oxidative damage in the colonic mucosa.Key words: Progesterone. Colitis. Inflammation. Colon. Rats. RESUMO OBJETIVO:Investigar os efeitos da progesterona em um modelo de colite experimental. MÉTODOS:Ratos albinos Wistar foram tratados subcutaneamente com 2mg/kg por dia durante sete dias. A colite foi induzida por administração intrarretal de 5mg ácido sulfônico trinitrobenzeno (TNBS). Foram avaliadas as atividades da doença, escores macroscópicos e microscópicos Para determinar a resposta provocada pela progesterona foi medida no cólon os níveis de malondialdeído (MDA), TNF alfa, IL-6 e óxido nítrico (NO), além da atividade da MPO (Myeloperoxidase) e caspase-3. RESULTADOS:A progesterone melhorou significantemente os escores macroscópicos e microscópicos. A colite induzida pelo TNBS significantemente aumentou os níveis colônicos de MDA e a atividade da caspase-3 no grupo 2 em comparação com o grupo controle.Os resultados do estudo revelaram um declínio nos níveis de MDA, NO, IL6 e TNF-α no tecido colônico e no sangue devido à terapia com a progesterona no grupo 3 quando comparado ao grupo 2. O tratamento com a progesterona foi associado com decréscimo do MDA, MPO, TNF alfa e atividade da caspase-3. CONCLUSÃO:A terapia com progesterona decresce o dano oxidativo na mucosa do cólon.Descritores: Progesterona. Colite. Inflamação. Colo. Ratos.Karatepe O et al.

Epidemiology of microscopic colitis

“…the presence of chronic watery diarrhoea and the absence of other gastrointestinal pathology leading to an increased IEL count or thickened collagen layer) was not available. The investigators were familiar with the symptomatic overlap between irritable bowel syndrome (IBS) and MC, 36 as well as the presence of MC-like inflammation in a large proportion of IBS patients, 37 but it was not possible to correct for this.…”

“…To be able to detect a potential effect, human peak plasma concentrations of diclofenac and omeprazole were doubled. 24,25 Only CC patients in remission were included as patients with active disease may already exhibit a disrupted epithelial barrier function due to the inflammatory process 37,38 and drug associations were stronger for CC than LC. In line with the in vitro experiments, Ussing chamber experiments showed no effect of diclofenac, omeprazole, or both on the paracellular permeability of healthy controls or CC cases.…”

“…33 Since the mid-'90s, several population-based epidemiological studies on the incidence of MC have been published. [34][35][36][37][38][39][40][41][42][43] Although the majority originates from Europe and NorthAmerica, incidence rates from other parts of the world have also been published. [44][45][46] World-wide, pooled incidence rates of 4.1 and 4.9 per 100,000 person years have been reported for CC and LC, respectively.…”

“…36 In MC patients an increased density of serotonin producing cells has been reported and increased serotonin concentrations have been found. 37,38 Findings from a study on serotonin transporter gene polymorphisms were contradictive, indicating these polymorphisms to be but one factor 4 contributing to the higher serotonin levels in MC. 38 Cause or bias?…”

“…Münch et al observed a residual barrier disruption might remain 6 weeks after achievement of clinical remission with oral budesonide. 37 However, this might be due to residual pro-inflammatory cytokines. It is unknown whether the barrier disruption lasts after a long period of clinical remission.…”