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.
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.
Subject(s)
Animals , Male , Rats , Colitis/prevention & control , Colon/drug effects , Progesterone/therapeutic use , Progestins/therapeutic use , Apoptosis/drug effects , Colitis/chemically induced , Colon/chemistry , Disease Models, Animal , Drug Evaluation, Preclinical , Intestinal Mucosa/drug effects , Malondialdehyde/analysis , Nitric Oxide/analysis , Rats, Wistar , Trinitrobenzenesulfonic AcidABSTRACT
PURPOSE: Evaluate the effects of iloprost administration in the early period of ischemic colitis and the mechanism that how these effects develop. METHODS: Thirty two Wistar albino female rats with an average weight of 220g were divided into four groups of eight rats. In group 1 the rats were given iloprost and sacrificed after 24 hours and in group 2 they were sacrificed after 24 hours without any iloprost. The rats in group 3 were administrated iloprost and sacrificed after 72 hours and in group 4 they were sacrificed at 72th hour without iloprost. The differences between the groups as tissue damage, vascularization or apoptosis were assessed statistically. RESULTS: Oxidative damage and apoptosis were less pronounced and vascularization was better developed in rats that were given iloprost and sacrificed at 24th hour later in contrast to the rats that were not treated with iloprost. But there was no statistical difference among the groups at 72th hour. CONCLUSION: Iloprost inhibited leucocyte infiltration, decreased proinflammatory cytokines and enhanced angiogenesis so that the oxidative stress and inflammatory response decreased resulting in lesser tissue damage.
OBJETIVO: Avaliar os efeitos da administração de iloprosta no período precoce da colite isquêmica e o mecanismo da evolução destes efeitos. MÉTODOS: Trinta e dois ratos Wistar fêmeas em torno de 220g foram distribuídos em quatro grupos de oito ratos. No grupo 1 administração de iloprosta e sacrificados após 24 horas; no grupo 2 foram sacrificados após 24 horas sem iloprosta; no grupo 3 foi administrado iloprosta e sacrificados após 72 horas; no grupo 4 foram sacrificados após 72 horas sem Iloprosta. As diferenças entre os grupos no referente a dano tecidual. vascularização ou apoptose foi apurada estatisticamente. RESULTADOS: Dano oxidativo e apoptose foram menos acentuados e a vascularização foi melhor nos ratos que receberam iloprosta e sacrificados após 24 horas em contraste com os ratos que não receberam iloprosta. Porém, não houve diferença estatisticamente significante entre os grupos de 72 horas. CONCLUSÃO: Iloprosta inibe infiltração leucocitária, diminui a ação inflamatória de citoquinas e estimula angiogênese resultando em menor dano tecidual.
Subject(s)
Animals , Colitis, Ischemic/veterinary , Rats/classification , Arachidonic Acid/adverse effects , Epoprostenol/administration & dosage , Iloprost/administration & dosageABSTRACT
BACKGROUND: Leakage from colonic anastomosis is a major complication causing increased mortality and morbidity. Ischemia is a well-known cause of this event. This study was designed to investigate the effects of adrenomedullin on the healing of ischemic colon anastomosis in a rat model. METHODS: Standardized left colon resection 3 cm above the peritoneal reflection and colonic anastomosis were performed in 40 Wistar rats that were divided into four groups. To mimic ischemia, the mesocolon was ligated 2 cm from either side of the anastomosis in all of the groups. The control groups (1 and 2) received no further treatment. The experimental groups (3 and 4) received adrenomedullin treatment. Adrenomedullin therapy was started in the perioperative period in group 3 and 4 rats (the therapeutic groups). Group 1 and group 3 rats were sacrificed on postoperative day 3. Group 2 and group 4 rats were sacrificed on postoperative day 7. After careful relaparotomy, bursting pressure, hydroxyproline, malondialdehyde, interleukin 6, nitric oxide, vascular endothelial growth factor, and tumor necrosis factor alpha levels were measured. Histopathological characteristics of the anastomosis were analyzed. RESULTS: The group 3 animals had a significantly higher bursting pressure than group 1 (p<0.05). Hydroxyproline levels in group 1 were significantly lower than in group 3 (p<0.05). The mean bursting pressure was significantly different between group 2 and group 4 (p<0.05). Hydroxyproline levels in groups 3 and 4 were significantly increased by adrenomedullin therapy relative to the control groups (p<0.05). When all groups were compared, malondialdehyde and nitric oxide were significantly lower in the control groups (p<0.05). When vascular endothelial growth factor levels were compared, no statistically significant difference between groups was observed. Interleukin 6 and tumor necrosis factor alpha were significantly decreased by adrenomedullin therapy (p<0.05). The healing parameters and inflammatory changes (e.g., granulocytic cell infiltration, necrosis, and exudate) were significantly different among all groups (p<0.05). CONCLUSION: Adrenomedullin had positive effects on histopathologic anastomotic healing in this experimental model of ischemic colon anastomosis.