Thesis (Ph. D.)--Georgia State University, 2007. / Title from title page. Lindsey L. Cohen, committee chair; Lisa Armistead, Erin B. McClure, Mary K. Morris, committee members. Electronic text (113 p. : ill. (some col.)) : digital, PDF file. Description based on contents viewed Oct. 11, 2007. Includes bibliographical references (p. 73-80).

It had long been known that individuals with inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), have locally reduced vitamin C levels in the intestinal mucosa, which equates to an overall loss of the antioxidant capacity and increase risk of oxidative tissue damage. The aim of the present work was to expand on this concept, through investigating the role of genetic variations in intestinal vitamin C transporters in vulnerability to IBD and further characterizing their functions. The studies focused on a known intestinal transporter for ascorbic acid, SLC23A1, and a novel intestinal transporter of dehydroascorbic acid, SLC2A14 (GLUT14). To investigate any association between the SLC23A1 and SLC2A14 with IBD, genomic DNA of 311 Caucasian individuals with IBD, participated in the Manitoba IBD Cohort Study, and 142 healthy controls were genotyped for tagging single nucleotide polymorphism (SNP) of each gene, using TaqMan Assays. New splice variants of SLC23A1 and SLC2A14 were determined by In silico analyses, followed by sub-cloning of the splice variants to verify their subcellular locations. Substrates and functions were determined, using the Xenopus laevis oocyte system for each transporter. The presence of the SLC23A1 variant rs10063949 G allele elevated the risk for CD by 150% (Odds ratios (OR) = 2.54, 95% CI 1.83-3.53). An allele dosage effect was confirmed; compared to rs10063949-AA homozygotes the 10063949-AG heterozygotes have a 150% elevated risk and the 10063949-GG homozygotes have a 370% elevated CD risk (OR=2.54, 95% CI 1.38-4.66; OR=4.72, 95% CI 2.53-8.81, p<0.001; respectively). No relation was observed between genetic variants in SLC23A1 and UC. Through database search, a novel 5’exon was discovered for SLC23A1 locus which is located 1078 nucleotides upstream of the canonical first exon. The two first exons are not mutually exclusive since they splice together to create a novel SLC23A1 protein isoform, we named it isoform 1A, with a N-terminus that is elongated by 36 amino acid. The novel SLC23A1 isoform located at the plasma membrane, but mediates only 7% of the ascorbic acid transport exhibited by the shorter isoform. The presence of the SLC2A14 SNP rs2889504 A allele elevated the risk for UC by 260% and CD by 468% (OR: 3.60, 95% CI: 1.95-6.64; OR: 4.68, 95% CI: 2.78-8.50, respectively). The rs10846086-G allele elevated the risk of UC and CD approximately 3-fold (OR: 2.91, 95% CI: 1.49-5.68; OR: 3.00, 95% CI: 1.55-5.78, respectively). The variant rs12815313-T increased the risk for CD by 112% (OR: 2.12, 95% CI: 1.33-3.36). All the genetic variations in SLC2A14 gene, associated with IBD, were independent from each other, strengthening the evidence that functional SNPs in the SLC2A14 locus contribute to IBD. It was identified that the two major GLUT14 isoforms locate to the plasmalemma membrane and mediate cellular uptake of dehydroascorbic acid. Significant expression in extra-testicular tissues was confirmed for SLC2A14, notably in intestinal segments, explaining the association with IBD. Re-analysis of genomic showed a dramatically expanded locus of SLC2A14, containing twenty exons which covered 103,477 nucleotides from the first Transcriptional Start Site (TSS) to the termination of the longest transcript. All together, the presented evidence indicate that functional SNPs in the SLC2A14 gene and SLC23A1 could contribute to vitamin C imbalance in mucosal cells which contributes to an elevated risks of IBD. Furthermore, novel information about genetic and functional characteristics of SLC23A1 and GLUT14 transporters was identified. / February 2016

BACKGROUND: Anemia is a common extra-intestinal manifestation of disease in patients with inflammatory bowel disease (IBD), and iron deficiency anemia (IDA) represents the most prevalent form of anemia in this population ((Gasche, Dejaco et al. 1997) (Plantz, Maxwell et al. 2016)). IDA can result from a combination of decreased dietary iron intake, impaired intestinal absorption, and excessive gastrointestinal (GI) bleeding, all of which can lead to decreased iron stores and poor iron utilization. Furthermore, chronic IDA in children with IBD can adversely influence development and cognition, as well as contribute to the increased fatigue and decreased stamina observed in these patients (Laass, Straub et al. 2014). Treatment of IDA in pediatric patients with IBD can be with either oral iron supplementation or parenteral iron infusions, and both can result in an improvement in iron parameters and subsequent improvement in patient overall quality of life. However, there is wide variability in physician practice with respect to the identification and treatment of IDA in pediatric patients with IBD. OBJECTIVE: To assess physician practice at Boston Children’s Hospital with respect to the identification and treatment of IBD-related IDA in a population of patients admitted for management of a flare in their underlying ulcerative colitis. This information will be useful to develop initiatives directed at improving recognition and management of IDA in this population. METHODS: The Institutional Review Board (IRB) at Boston Children's Hospital (BCH) approved the study protocol. Patient electronic medical records were reviewed and abstracted from subjects with ulcerative colitis (UC) that were treated at BCH between January 2005 and January 2013. Each patient was assigned a study identification number to protect private health information, and this data was stored in a computer file behind the hospital’s internet firewall. Inpatient and outpatient office notes, as well as clinical data, were reviewed to track the identification of patients with anemia as well as physician management practices. All of the information collected was stored in the Research Electronic Database Capture (REDCap) and used for analysis. RESULTS: A total of 243 patients met initial inclusion criteria. Subsequent review of the electronic medical records revealed that only 178 patients had complete data available for use in our analysis. 55.5% of the 178 study subjects were anemic at admission, with a mean hemoglobin value of 9.32 g/dL (SD 1.89) and a mean MCV value of 77.49 fl (SD 10.24). None of the patients in this cohort had iron studies (plasma iron, ferritin, total iron binding capacity) included in their admissions laboratory testing. Only 24 patients received oral iron supplementation during their hospital stay while none received IV iron infusions. Over half of the total patient cohort (78.7 %,) were not prescribed oral iron supplementation at the time of discharge. 84% of patients that were discharged anemic remained anemic at the time of their first post-discharge ambulatory visit. Less than half of the total patient cohort (30.34%) had iron studies included in their follow-up ambulatory laboratory testing. Patients that were given iron supplementation at the time of discharge showed increased gains in their hemoglobin levels at follow-up compared to patients with no iron supplementation at the time of discharge (p <0.0001). CONCLUSION: These data suggest that there is a low prevalence with respect to the identification and treatment of IDA and anemia in pediatric patients with ulcerative colitis (UC) at admission, discharge, and follow-up clinic visits. A secondary finding was a statistically significant increase in hemoglobin levels in anemic patients treated with some form of iron supplementation. As a result, our data support both the need to improve recognition of IDA in pediatric patients admitted for a UC flare as well as document the clinical value to this effort. Additional studies are necessary to determine if improved iron surveillance and therapy will improve patient quality of life, linear growth, and cognition in patients with IBD.

Patients with inflammatory bowel disease, particularly those on systemic immunosuppression, have been shown to be at increased risk of herpes zoster infection. Herpes zoster (also known as shingles) is a condition resulting from reactivation of varicella zoster virus (VZV), which causes chickenpox. VZV reactivation is thought to be due to impairment of cell-mediated immunity. Some immunosuppressive agents have been shown to be associated with higher risk for herpes zoster reactivation than others. Until recently, the only vaccine for herpes zoster was a live-attenuated vaccine, which is contraindicated in most immunosuppressed IBD patients due to their immunosuppressive therapy. Recently, an inactivated subunit vaccine has been developed and investigated for use in immunocompetent adults, as well as select groups of immunocompromised individuals. This novel vaccine has not yet been studied in IBD patients but holds promise for use in this population. The proposed study is a single-center prospective pilot study comparing immunogenicity and safety of the inactivated herpes zoster vaccine in patients with IBD (ulcerative colitis or Crohn’s disease) treated with high-level combination immunosuppression (both anti-TNF biologics and immunomodulators) to those not on systemic immunosuppressive therapy (5-aminosalicylates or no treatment). Investigators will compare cell-mediated responses between groups using an intracellular cytokine staining assay with flow cytometry assessed prior to vaccination and at four time points up to 12 months after completion of the immunization sequence. Adverse effects will also be monitored. This study will help to identify whether the novel herpes zoster vaccine is immunogenic and safe for use in IBD patients and whether these parameters are significantly impacted by intensity of immunosuppressive treatment. An additional goal is to provide preliminary data with which to develop future studies of vaccine immunogenicity and efficacy in this target population.

Paediatric intestinal failure following bowel resection causes significant morbidity and mortality. There is a pressing need for improved treatment modalities. Following loss of bowel, the remaining intestine undergoes a period of adaptation, characterised by an increase in height of the intestinal villi. Better understanding the factors that govern the formation and growth of villi may lead to therapeutic interventions that amplify the intrinsic adaptation response. This thesis aims to explore the processes by which intestinal villi form during embryological development, the contribution of intestinal stem cells to this, and candidate signalling pathways that may yield insights into new therapeutic interventions for patients with intestinal failure. Abstract: Aim I will examine the morphogenesis and morphology of intestinal villi by investigating three themes: 1) Villus morphogenesis: When and where do villi form along the gut tube? Can this process be quantified, both in vivo and in vitro? Is this initiated by a dominolike signaling-cascade along the bowel, or location-specific intrinsic triggers? 2) Stem cells: What is the spatiotemporal appearance of the Lgr5-expressing intestinal stem cells during development? How does this relate to the process of villus morphogenesis? 3) Signalling pathways: Can a genetic mutation mouse model help elucidate pathways by which post bowel resection adaptation might occur? Can this be used to help identify potential intestinotrophic agents? Abstract: Materials and Methods Three mice models were used as the foundation for this work. Embryonic tissue was analysed from wild-type CD1 and Lgr5-eGFP-IRES-CreERT2 mice, and adult intestinal tissue examined from tamoxifen-activated Villin-Cre-ERT2 Pten-/- Brafv600E mice. Culture of wild-type embryonic mouse intestine with and without segments removed and / or reversed was performed to investigate the question of what triggers the proximal-to-distal wave of villus morphogenesis. Immunohistochemical interrogation using anti-GFP antibodies was used in the Lgr5- GFP mice to identify the location of Lgr5-expressing cells during the development of villi. Bright-field microscopy, time-lapse in-incubator microscopy, and histological sections assessed villus morphology. The Villin-Cre-ERT2 Pten-/- Brafv600E mouse mutant was explored regarding the intestinal epithelial morphometric changes that occur following tamoxifen-induction. Abstract: Results The proximal-to-distal wave of villus morphogenesis was observed both in vivo and in vitro. Villus morphogenesis commences at embryonic day 14.5 in vivo and after three days in culture from e11.5 in vitro. The villus structures formed in vitro are significantly attenuated compared to in vivo development. An attempt was made to overcome this by providing intestinal explants with a blood supply to aid growth. Evidence is presented that suggest the proximal-to-distal wave of villus morphogenesis is driven by location specific factors intrinsic to each part of the bowel, rather than a domino-like signalling cascade travelling along the intestine. Lgr5-expressing intestinal stem cells were present in early development. Prior to villus morphogenesis they were uniformly distributed along the luminal surface of the intestinal epithelia. During the intense proliferation associated with villus morphogenesis they progressively congregated to the inter-villus spaces. Once villi are fully formed they were absent from the villi but identified in the inter-villus spaces. The Pten/Braf mouse mutant demonstrates villus morphological changes similar to those found following post-bowel resection adaptation. This suggests that there may be a role for Pten/Braf in the epithelial proliferation following extensive bowel resection. Signalling factors in these pathways may be candidate intestinotrophic agents for the treatment of short bowel syndrome. Abstract: Conclusions Before any processes that manipulate intestinal epithelia can be safely translated into therapies to aid adaptation in patients with intestinal failure, it is important to have a full and detailed understanding of the basic science principles that underpin the behaviour of the epithelial cells, both during development and in adulthood. I have explored and quantified the process of villus morphogenesis in the embryonic mouse, investigated the timing of appearance of Lgr5 intestinal stem cells, and interrogated a genetic mouse model with morphometric changes similar to those seen following small bowel resection. I propose two candidate intestinotrophic agents that may hold regenerative potential to augment post small bowel resection adaptation. The next stage of investigation would be to use a mouse model of small bowel resection with manipulation of cell signalling factors to assess impact on post resection adaptation. The ultimate goal would be to investigate epithelial activity in human neonatal intestine and explore methods of modulating this to improve the outcomes from post bowel resection intestinal failure.

Background: An ex vivo experimental strategy replicating in vivo intestinal development would provide an accessible setting to study normal and dysmorphic biology, and would be a test bed for tissue engineering. Previous studies implicated transforming growth factor β1 (TGFβ1) in postnatal gut maturation and regeneration following injury, but its potential role in intestinal development is poorly understood. I firstly hypothesised that embryonic small intestine is able to heal after physical injury. To test this idea, I aimed to create an organ culture model using explants of embryonic jejunum. I secondly hypothesised that TGFβ1 affects embryonic small intestine growth and differentiation. Accordingly, I aimed to use the same organ culture model to determine potential effects of exogenous TGFβ1.Methods. Segments of mouse embryonic jejunum were isolated by dissection and placed on semipermeable platforms. They were fed with defined, serum free, media, in some cases supplemented with TGFβ1. Growth, differentiation and healing of explants were characterized and quantified using a battery of techniques that included whole mount imaging, histology, immunostaining and RNA arrays. TGFβ1 was measured in amniotic fluid by enzyme-linked immunosorbent assay. Groups were compared by statistical tests. Results: After three days of culture, jejunal rudiments differentiated from simple tubes into a more complex structures containing smooth muscle surrounding newly formed villi. Pairs of rudiments, linked by a thread, fused and formed a continuous single lumen, as assessed by trajectories of fluorescent dextrans injected into their distal ends. Functional continuity was confirmed by spontaneous waves of peristalsis crossing the point of fusion. In vivo, TGFβ receptors I and II were detected in embryonic longitudinal smooth muscle cells and, in organ culture, exogenous TGFβ1 induced differentiation of longitudinal smooth muscle. Microarray profiling showed that TGFβ1 increased smooth muscle associated transcripts in a dose-dependent manner. TGFβ1 protein was detected in amniotic fluid at a time when the embryonic small intestine was physiologically herniated. Conclusion: Embryonic jejunal segments can fuse to form a single functional organ when aided by a mechanical manipulation. By analogy with the requirement for exogenous TGFβ1 for smooth muscle differentiation in culture, the TGFβ1 protein that I demonstrated to be present in the amniotic fluid may enhance intestinal development when it is physiologically herniated in early gestation. Future studies of embryonic intestinal cultures should add TGFβ1 in the defined media to produce a more faithful model of in vivo muscle differentiation. In future, this model could be used to test whether other growth factors enhance intestinal growth, and so pave the way to novel biological treatments for short bowel syndrome, a devastating disease with a high mortality.

Made available in DSpace on 2014-06-11T19:25:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-09-03Bitstream added on 2014-06-13T20:53:16Z : No. of bitstreams: 1 simoncini_vs_me_botib.pdf: 667182 bytes, checksum: 02774471f02be04fbff31c82acb30112 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / A Doença Inflamatória Intestinal (DII) engloba uma série de doenças que afetam o trato intestinal, especialmente o cólon, sendo as principais a retocolite ulcerativa e a doença de Crohn, ambas com alta taxa de morbidade e mortalidade, além de representarem um dos mais importantes fatores de risco para o câncer colorretal, que no Brasil é o quarto tipo de tumor com maior incidência de mortes. Inúmeros medicamentos são usados no controle e no tratamento destas doenças (aminosalicilatos, glicocorticóides, imunomoduladores e antibióticos), no entanto, todos apresentam sérios efeitos colaterais e são de custo extremamente elevado. Além da busca por novas drogas para o tratamento destas doenças ainda sem cura, uma importante estratégia preventiva e curativa se baseia no uso de prebióticos na dieta, os quais poderiam tanto melhorar as condições de vida do paciente como permitir por efeito sinérgico a redução das doses dos fármacos comumente utilizados nestas doenças e conseqüentemente de seus efeitos adversos e tóxicos. Com base nestas informações, o presente trabalho visou 1. Avaliar os efeitos preventivos da dieta enriquecida com banana verde (Banana „Nanica‟ Musa sp AAA) na colite ulcerativa experimental induzida por ácido trinitrobenzenosulfônico em ratos; 2. Avaliar a influência do uso da dieta enriquecida com banana verde sobre a atividade antiinflamatória da prednisolona; 3. Comprovar se a dieta enriquecida com banana verde pode ser considerada um prebiótico. Através da realização deste estudo foi possível concluir que a administração da dieta enriquecida com a banana verde nas concentrações de 10% e 20% protege o cólon de ratos da colite experimental através de mecanismo que envolve a diminuição do estresse oxidativo evidenciado com a manutenção dos níveis de glutationa; além disso, a dieta enriquecida não aumenta a atividade... / The inflammatory bowel disease (IBD) consists in two major diseases that affect the gastrointestinal tract, specially the colon, ulcerative colitis and Crohn‟s disease, both with high mortality and morbity. These diseases represent a major risk for the development of colorectal cancer, which, in Brazil is correlated with a high mortality. Many drugs are used to control these illnesses but most of them present serious side effects and/or are very expensive. The search of new drugs is still a viable method to discovery different treatments for IBD however a new preventive and curative method can be the use of prebiotics. These prebiotics can improve the patients‟ life conditions and possibly permit the decrease of the drugs doses that are used and consequently side and toxics effects. In light of this, the aims of the present study was to evaluate the preventive effects of dietary supplementation with green banana (Banana „Nanica‟ Musa sp AAA) in experimental models of rat colitis induced by trinitrobenzenesulphonic acid (TNBS), evaluate the influence of the dietary supplementation in the dose of a corticoid (prednisolone) and then be able to analyze if the dietary supplementation can be considerate a prebiotic. Our results revealed that the ingestion of the dietary supplementation with green banana in 10% and 20% showed significant anti-inflammatory activities in the experimental model of rat colitis induced by TNBS. This activity was related with the reduction of the oxidative stress indicated with the maintenance of glutathione levels; besides, the anti-inflammatory activity of prednisolone was not altered with the dietary supplementation and the anti inflammatory preventive effects of the dietary supplementation was not correlated with a prebiotic activity

Made available in DSpace on 2014-06-11T19:25:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28Bitstream added on 2014-06-13T20:53:16Z : No. of bitstreams: 1 almeidajunior_ld_me_botib_parcial.pdf: 353637 bytes, checksum: e154d67d475601f9d66edd862735410a (MD5) Bitstreams deleted on 2015-02-04T11:39:27Z: almeidajunior_ld_me_botib_parcial.pdf,Bitstream added on 2015-02-04T11:40:12Z : No. of bitstreams: 1 000725128.pdf: 1021495 bytes, checksum: 10e5b8e91e721bace643318731693faa (MD5) / A Doença Inflamatória Intestinal (DII) é uma doença com etiologia desconhecida e sem terapêutica curativa disponível, englobando, fundamentalmente, duas doenças distintas: a Doença de Crohn (DC) e a Retocolite Ulcerativa (RCU), ambas caracterizadas por uma inflamação crônica do intestino, com períodos de exacerbação seguidos de intervalos prolongados com remissão dos sintomas, cujo tratamento com os fármacos disponíveis apresentam sérios efeitos colaterais. Portanto, o desenvolvimento de novas estratégias de tratamento que combinem eficácia e segurança é uma importante meta na terapia da DII, sendo que as plantas medicinais são indispensáveis fontes de novos compostos de valor terapêutico. Physalis angulata L. é uma planta nativa brasileira que cresce especialmente nas regiões norte e nordeste do Brasil e em outros países tropicais da África, América e Ásia, sendo amplamente utilizada pela população para o tratamento de uma série de doenças, especialmente aquelas que possuem características inflamatórias. Estudos in vitro em culturas de células realizados por nosso grupo de pesquisa, somados aos dados descritos na literatura mostram que a P. angulata é capaz de modular vários mediadores inflamatórios. Dessa forma, o objetivo deste trabalho foi avaliar a atividade anti-inflamatória intestinal do extrato padronizado em fitoesteróis totais de P. angulata, nas fases aguda e crônica (com recidiva) do processo inflamatório intestinal induzido por acido trinitrobenzenosulfônico (TNBS) em ratos. Os resultados obtidos mostraram, pela primeira vez, que o extrato padronizado produziu uma série de efeitos que melhoraram a resposta dos animais frente à lesão intestinal promovida pelo TNBS. Estes efeitos foram mais pronunciados nos estudos de fase aguda, indicando uma propriedade preventiva importante... / Inflammatory Bowel Disease (IBD) is a disease with unknown etiology and no curative treatment available, embracing essentially two distinct diseases: Crohn's disease (CD) and ulcerative colitis (UC), both characterized by chronic inflammation of the intestine, with periods of exacerbation followed by long intervals with symptom remission, whose treatment with available drugs have serious side effects. Therefore, the development of new treatment strategies that combine effectiveness and safety is an important goal in the treatment of IBD, where medicinal plants are sources of essential novel compounds of therapeutic value. Physalis angulata L. is a native Brazilian plant that grows especially in Northern and Northeastern Brazil and other tropical countries of Africa, America and Asia and is widely used by people to treat a number of diseases, especially those with inflammatory characteristics. In vitro studies in cell cultures conducted by our research group, combined with the previously reported data, show that P. angulata is capable of modulating several inflammatory mediators. Thus, the objective of this study was to evaluate the intestinal anti-inflammatory activity of P. angulata standardized extract in total phytosterols, in the acute and chronic (with relapse) phases of the intestinal inflammatory process induced by trinitrobenzene sulfonic acid (TNBS) in rats. The results showed, for the first time, that the standardized extract produced a series of effects that improved the response of animals against intestinal injury promoted by TNBS. These effects were more pronounced in the acute studies, indicating an important preventive property by reducing the activity of myeloperoxidase and alkaline phosphatase, in addition with the ability of the extract to prevent depletion of glutathione induced by intestinal... (Complete abstract click electronic access below)

Made available in DSpace on 2014-06-11T19:32:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2010Bitstream added on 2014-06-13T20:03:08Z : No. of bitstreams: 1 witaicenis_a_dr_botib.pdf: 2812216 bytes, checksum: 889ab136e47219cee54a1e64f718d6cf (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Not available

Made available in DSpace on 2014-06-11T19:32:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-05-30Bitstream added on 2014-06-13T20:03:08Z : No. of bitstreams: 1 kushima_h_dr_botib.pdf: 1089562 bytes, checksum: 1afece4aabc68a6b84aa6879f8e72585 (MD5) / A doença inflamatória intestinal (DII) corresponde a um conjunto de desordens crônicas inflamatórias intestinais, de etiologia ainda desconhecida, sendo a retocolite (RCU) e a doença de Crohn (DC) as duas doenças mais representativas e de maior importância clínica. Devido a pouca eficácia das terapias convencionais, muitos pacientes recorrem a métodos alternativos, como o uso de plantas medicinais. As espécies Davilla elliptica St. Hil e Davilla nitida (Vahl) Kubitzki (família Dilleniaceae) são plantas arbustivas comumente encontradas no Cerrado brasileiro. D. elliptica, conhecida como lixeirinha, é utilizada na medicina popular para o tratamento de afecções do trato gastrointestinal, como úlceras e gastrites, e também utilizado como antiinflamatório. D. nitida (cipó de fogo) apresenta um grande potencial para o tratamento de doenças do trato gastrointestinal, pois semelhante a D. elliptica, apresenta comprovada ação gastroprotetora e ambas possuem perfis fitoquímicos semelhantes, compostos basicamente de polifenóis. Os objetivos deste trabalho foram avaliar os efeitos preventivos e/ou curativos dos extratos metanólicos de D. elliptica (EDE) e D. nitida (EDN) em modelos experimentais de colite (agudo e crônico) induzidos pelo ácido trinitrobenzenosulfônico (TNBS) em ratos e os possíveis mecanismos decorrentes dessas ações farmacológicas. A partir dos resultados anteriormente obtidos da ação gastroprotetora de ambos os extratos, foram selecionadas as doses empregadas nos modelos experimentais de colite. Foi constatado que altas doses (500 mg/kg) de EDE e EDN administradas oralmente, promovem o agravamento das injúrias no cólon (aumento de 47 e 21% das lesões, respectivamente). Porém, ao avaliar os efeitos agudos de ambos os extratos no modelo de colite com doses menores (31.2, 62.5 e 125 mg/kg), ocorreram reduções significativas das áreas... / Inflammatory bowel disease (DII) represents a group of chronic inflammatory bowel disorders of unknown etiology, and ulcerative colitis (RCU) and Crohn's disease (DC) both diseases are most representative and important among the DII clinic. Because the conventional therapies ineffectiveness, many patients resort to alternative methods, such as the use of medicinal plants. The species Davilla elliptica St. Hil and Davilla nitida (Vahl) Kubitzki (family Dilleniaceae) are shrubs commonly found in the Brazilian Cerrado. D. elliptica, known as “lixeirinha”, is used in folk medicine for the gastrointestinal disorders treatment such as gastritis and ulcers and also used as antiinflammatory. D. nitida (“cipó de fogo”) has great potential to treat gastrointestinal diseases, thus similar to D. elliptica, has proven gastroprotective action and both have similar phytochemical profiles, composed primarily of polyphenols. Our objectives were to evaluate the preventive and/or healing effects of the D. elliptica (EDE) and D. nitida (EDN) methanolic extracts in the colite experimental models (acute and chronic) induced by trinitrobenzenesulfonic acid (TNBS) in rats and possible mechanisms resulting from these pharmacological actions. From the previous results of gastroprotective action of both extracts, we selected the doses used in experimental models of UC. It was found that high doses (500 mg / kg) of EDN and EDE administered orally, promoted the colon injury aggravation (lesion increasing of 47 and 21%, respectively). However, in assessing the acute effects of both extracts in the UC model at lower doses (31.2, 62.5 and 125 mg/kg), there were significant reductions in areas (for both extracts) and scores of the injuries (EDN only) promoted by TNBS. The colonic lesions reduction in the animals treated with EDE and EDN did not alter the weight/length parameter of colon and feed... (Complete abstract click electronic access below)