RESUMEN
BACKGROUNDS: Berberine (BBR), a compound long used in traditional Chinese medicine, has been reported to have therapeutic effects in treating ulcerative colitis (UC), attributed to its anti-inflammatory properties and restorative potential of tight junctions (TJs). However, the mechanism by which BBR affects intestinal bacteria and immunity is still unclear. METHODS: This study investigated the effects of BBR on intestinal bacteria and the inflammatory response in dextran sulfate sodium (DSS)-induced colitis mice. Immunohistochemistry (IHC) and electron microscopy were used to detect intestinal TJs. Microflora analysis was used to screen for bacteria regulated by BBR. RESULTS: The results showed that BBR had increased colonic epithelium zonula occludens proteins-1 (ZO-1) and occludin expression and reduced T-helper 17/T regulatory ratio in DSS-induced mice. Mechanically, BBR eliminated DSS-induced intestinal flora disturbances in mice, particularly increased Bacteroides fragilis (B. fragilis) in vivo and in vitro. B. fragilis decreased the interleukin-6 induced by dendritic cells through some heat-resistant component rather than nucleic acids or proteins. CONCLUSIONS: Overall, these data suggest that BBR had a moderating effect on DSS-induced colitis. This compound may regulate intestinal immune cell differentiation by affecting the growth of B. fragilis, providing new insights into the potential application of BBR in UC.
Asunto(s)
Antiinflamatorios/farmacología , Bacteroides fragilis/efectos de los fármacos , Berberina/farmacología , Diferenciación Celular/efectos de los fármacos , Colitis/tratamiento farmacológico , Células Dendríticas/efectos de los fármacos , Animales , Antiinflamatorios/uso terapéutico , Bacteroides fragilis/crecimiento & desarrollo , Berberina/uso terapéutico , Colitis/inducido químicamente , Colitis Ulcerosa/patología , Colon/ultraestructura , Citocinas/metabolismo , Sulfato de Dextran/farmacología , Citometría de Flujo , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Mucosa Intestinal/patología , Mucosa Intestinal/ultraestructura , Ratones , Microscopía Electrónica de Transmisión , Reacción en Cadena en Tiempo Real de la Polimerasa , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/ultraestructuraRESUMEN
Intestinal epithelial cell (IEC) damage by T cells contributes to graft-versus-host disease, inflammatory bowel disease and immune checkpoint blockade-mediated colitis. But little is known about the target cell-intrinsic features that affect disease severity. Here we identified disruption of oxidative phosphorylation and an increase in succinate levels in the IECs from several distinct in vivo models of T cell-mediated colitis. Metabolic flux studies, complemented by imaging and protein analyses, identified disruption of IEC-intrinsic succinate dehydrogenase A (SDHA), a component of mitochondrial complex II, in causing these metabolic alterations. The relevance of IEC-intrinsic SDHA in mediating disease severity was confirmed by complementary chemical and genetic experimental approaches and validated in human clinical samples. These data identify a critical role for the alteration of the IEC-specific mitochondrial complex II component SDHA in the regulation of the severity of T cell-mediated intestinal diseases.
Asunto(s)
Colitis/enzimología , Colon/enzimología , Citotoxicidad Inmunológica , Complejo II de Transporte de Electrones/metabolismo , Células Epiteliales/enzimología , Enfermedad Injerto contra Huésped/enzimología , Mucosa Intestinal/enzimología , Mitocondrias/enzimología , Linfocitos T/inmunología , Animales , Estudios de Casos y Controles , Comunicación Celular , Células Cultivadas , Colitis/genética , Colitis/inmunología , Colitis/patología , Colon/inmunología , Colon/ultraestructura , Modelos Animales de Enfermedad , Complejo II de Transporte de Electrones/genética , Células Epiteliales/inmunología , Células Epiteliales/ultraestructura , Femenino , Enfermedad Injerto contra Huésped/genética , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Humanos , Inmunidad Mucosa , Mucosa Intestinal/inmunología , Mucosa Intestinal/ultraestructura , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Transgénicos , Mitocondrias/inmunología , Mitocondrias/ultraestructura , Fosforilación Oxidativa , Ácido Succínico/metabolismo , Linfocitos T/metabolismoRESUMEN
BACKGROUND: Feiyangchangweiyan capsule (FYC) is a traditional Chinese medicine formulation used in the clinical treatment of acute and chronic gastroenteritis and bacterial dysentery. However, the effect of FYC on ulcerative colitis (UC) and the mechanism thereof remains unknown. PURPOSE: To investigate the protective effect of FYC on UC mice induced by dextran sulfate sodium and illustrate the potential mechanism of this effect. METHODS: Here, we established a model of UC mice by dextran sulfate sodium and administered with FYC. The disease activity index (DAI), colon length, myeloperoxidase (MPO) content in serum, pathological structure and ultrastructural changes, and inflammatory cell infiltration of colon tissue were evaluated. Transcriptome and 16S rDNA sequencing were employed to illuminate the mechanism of FYC in the protection of UC mice. RESULTS: FYC significantly alleviates the pathological damage and the infiltration of inflammatory cells in colon tissue of dextran sulfate sodium induced UC mice, rescues shortened colon length, reduces DAI score, MPO content in serum, and pro-inflammatory factors including IL-1ß, IL-6, CCL11, MCP-1 and MIP-2, and increases anti-inflammatory factors such as IL-10. Transcriptomics revealed that Oncostatin M (OSM) and its receptor (OSMR) are the critical pathway for UC treatment by FYC. OSM and OSMR increased in UC mice compared to control mice, and decreased with FYC, which was verified via measurement of OSM and OSMR mRNA and protein levels. Furthermore, we observed that FYC modulates intestinal microbiome composition (e.g., the proportion of Barnesiella/Proteobacteria) by affecting the inflammatory factors. CONCLUSION: FYC exerts an effect on UC by inhibiting the OSM/OSMR pathway and regulating inflammatory factors to improve the intestinal flora.
Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Subunidad beta del Receptor de Oncostatina M/metabolismo , Oncostatina M/metabolismo , Animales , Antiinflamatorios no Esteroideos/farmacología , Cápsulas , Quimiocinas/sangre , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/microbiología , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Colon/ultraestructura , Citocinas/sangre , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Microbioma Gastrointestinal/genética , Masculino , Ratones Endogámicos C57BL , Oncostatina M/genética , Subunidad beta del Receptor de Oncostatina M/genética , Sustancias Protectoras/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Huai hua san (HHS) is a traditional Chinese herbal formula which is firstly documented in the ancient Chinese classic medical work "Pu Ji Ben Shi Fang" in 1132 AD. It has been widely used in the treatment of lower gastrointestinal disorders such as acute colitis and hematochezia for more than 800 years. However, scientific evidence of the efficacy and the exact mechanism of HHS against colitis has not yet been reported. AIM OF THE STUDY: The aim of this study is to investigate the potential effects of HHS in the alleviation of dextran sulphate sodium (DSS)-induced colitis and the alteration of colonic microbiota composition and structure. MATERIALS AND METHODS: HHS solution was orally administrated to 5% DSS-challenged rats once a day for 8 days. Colitis clinical symptoms of colitis were collected, together with colonic mucosal damage assessed at histomorphometric and ultrastructural levels. The protein levels of inflammatory mediators TNF-α and CRP were detected by ELISA. The colonic vascular permeability was evaluated by Evans blue extravasation. Meanwhile, The effects of the HHS therapy on the colonic microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods. RESULTS: Daily oral administration of HHS markedly alleviated DSS-induced colitis, as evidenced by decreased colitis disease activity index (DAI) score, reduced colonic inflammation and normalization of colonic vascular hyperpermeability. Moreover, the 16S rRNA gene sequencing analysis demonstrated that HHS treatment during colitis prevented the colitis-associated alteration of colonic microbial community at operational taxonomic unit level, together with the DSS-induced colonic microbiota dysbiosis at taxonomic levels. In addition, HHS therapy reduced colitis-associated high increased ratio of Bacteroidetes to Firmicutes to a normal level. CONCLUSION: HHS could attenuate ulcerative colitis and ameliorate gut microbial dysbiosis.
Asunto(s)
Antiinflamatorios/farmacología , Bacterias/efectos de los fármacos , Colitis/tratamiento farmacológico , Colon/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Bacterias/clasificación , Bacterias/crecimiento & desarrollo , Proteínas Portadoras/metabolismo , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/microbiología , Colon/metabolismo , Colon/microbiología , Colon/ultraestructura , Sulfato de Dextran , Modelos Animales de Enfermedad , Disbiosis , Mediadores de Inflamación/metabolismo , Masculino , Permeabilidad , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: To investigate effects moxibustion exerts on A20 expression and regulation of intestinal epithelial tight junctions via the TNF-α-NF-κB-MLCK pathway in Crohn's disease (CD). METHODS: C57BL/6 wild type (WT) and A20IEC-KO mice (48 each) were randomly divided into normal control (NC), model control (MC), mesalazine (MESA) and herbs-partitioned moxibustion (HPM) groups (12 mice per group). An experimental model of CD was established using 2, 4, 6 trinitrobenzene sulfonic acid. MESA and HPM mice were treated with MESA and HPM (at Tianshu (ST25) and Qihai (CV6)), respectively. In HPM group, moxa cones (0.5â¯cm in diameter and 0.3â¯cm in height) made of refined mugwort floss were placed on herbal cakes (medicinal formula dispensing [radix] Aconiti praeparata, [cortex] Cinnamomi, etc.) at Tianshu (ST25) and Qihai (CV6) and ignited. The moxa cones were ignited, and two moxa cones were used for each treatment once daily for 10 days. In MESA group, mice were fed MESA, which was prepared at a proportion of 1:0.0026, twice daily for 10 days. RESULTS: Intestinal epithelial ultrastructure of WT HPM mice improved more than A20IEC-KO HPM mice compared to MC mice. WT HPM mice exhibited greater expression of A20 compared with MC mice (Pâ¯<â¯0.01). TNF-α, NF-kB p65, MLCK, MLC, TRAF6 and RIP1 levels in A20IEC-KO and WT HPM mice were all decreased compared to MC mice (Pallâ¯<â¯0.01). NF-κB p65ãMLCK and TRAF6 levels were increased in A20IEC-KO HPM mice as compared to WT HPM mice (Pallâ¯<â¯0.05). Intestinal epithelial levels of occludin, claudin-1, ZO-1 and F-actin increased in all HPM mice (Pall⯠<â¯0.01-0.05), while occludin, claudin-1, and ZO-1 levels were lower in A20 IEC-KO HPM mice (Pâ¯<â¯0.05, Pâ¯<â¯0.01, Pâ¯<â¯0.01). CONCLUSION: HPM downregulates abnormal activation of the TNF-α-NF-κB-MLCK pathway by upregulating expression of A20 in a mouse model of CD, thereby protecting intestinal epithelial tight junctions and repairing the damage CD causes to the intestinal epithelial barrier.
Asunto(s)
Artemisia/química , Enfermedad de Crohn/terapia , Mucosa Intestinal/ultraestructura , Moxibustión/métodos , Uniones Estrechas/ultraestructura , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/metabolismo , Animales , Colon/metabolismo , Colon/ultraestructura , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , Modelos Animales de Enfermedad , Células Epiteliales/metabolismo , Células Epiteliales/patología , Mucosa Intestinal/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Permeabilidad , Uniones Estrechas/metabolismo , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa/genética , Regulación hacia ArribaRESUMEN
Inflammatory bowel diseases (IBD) are a chronic inflammatory disorders with increasing global incidence. Synbiotic, which is a two-point approach carrying probiotic and prebiotic components in mitigating inflammation in IBD, is thought to be a pragmatic approach owing to the synergistic outcomes. In this study, the impacts of dietary supplementation with probiotic Bacillus coagulans MTCC5856 spores (B. coagulans) and prebiotic whole plant sugar cane fibre (PSCF) was assessed using a murine model of IBD. Eight-week-old C57BL/6 mice were fed a normal chow diet supplemented with either B. coagulans, PSCF or its synbiotic combination. After seven days of supplementation, colitis was induced with dextran sulfate sodium (DSS) in drinking water for seven days during the continuation of the supplemented diets. Synbiotic supplementation ameliorated disease activity index and histological score (-72%, 7.38, respectively), more effectively than either B. coagulans (-47%, 10.1) and PSCF (-53%, 13.0) alone. Synbiotic supplementation also significantly (p < 0.0001) prevented the expression of tight junction proteins and modulated the altered serum IL-1ß (-40%), IL-10 (+26%), and C-reactive protein (CRP) (-39%) levels. Synbiotic supplementations also raised the short-chain fatty acids (SCFA) profile more extensively compared to the unsupplemented DSS-control. The synbiotic health outcome effect of the probiotic and prebiotic combinations may be associated with a synergistic direct immune-regulating efficacy of the components, their ability to protect epithelial integrity, stimulation of probiotic spores by the prebiotic fibre, and/or with stimulation of greater levels of fermentation of fibres releasing SCFAs that mediate the reduction in colonic inflammation. Our model findings suggest synbiotic supplementation should be tested in clinical trials.
Asunto(s)
Fibras de la Dieta/administración & dosificación , Enfermedades Inflamatorias del Intestino/terapia , Probióticos/administración & dosificación , Saccharum , Esporas Bacterianas , Simbióticos/administración & dosificación , Animales , Bacillus coagulans , Proteína C-Reactiva/análisis , Colon/ultraestructura , Dieta , Suplementos Dietéticos , Modelos Animales de Enfermedad , Femenino , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/patología , Interleucina-1beta/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Uniones Estrechas/patologíaRESUMEN
Ulcerative colitis (UC), a form of inflammatory bowel disease (IBD), is an immune-modulated disorder characterized by chronic and recurring inflammatory episodes. Oxidative stress and COX pathway of prostaglandin (PG) biosynthesis are indispensable to pathogenesis of UC. Any imbalance between PGs can compromise the mucosal homeostasis, leading to mucosal damage and chronic inflammation. However, blocking these PGs using classical Cox inhibitors such as non-steroidal anti-inflammatory drugs (NSAIDs) can instead aggravate signs of IBD. Therefore, realizing the need for safer and well tolerable alterative treatment approaches, currently, we evaluated the efficacy of n-3 fatty acids rich fish oil (FO) in the resolution of UC. Using a dextran sodium sulfate (DSS) model of experimental colitis, we have demonstrated that supplementation of FO containing 180 mg EPA and 120 mg DHA for 1 month relieved the signs (diarrhea, bloody stools, weight loss) of colitis-associated inflammation. To understand the biophysical changes associated with FO mediated inflammatory regulation, impedance measurement and Fourier transform infrared spectroscopy (FTIR) were done. These changes were also correlated with oxidative stress through markers such as GST, glutathione peroxidase (GPx), LPO, catalase, protein carbonyl content, GR, etc. in colonic mucosa. The modulation of COX mediated pathways in UC-associated inflammation was observed by protein expressions of various pro-inflammatory cytokines such as TNF-α and enzymes of PG synthesis such as COX-2, PGES, TXAS, and anti-inflammatory PGDS. Refuting the earlier reports that suggested the contradictory effects of FO, in the current study, we evidently demonstrated that the protective effects of FO are mediated through molecular mechanisms involving the redox-regulation of metabolism of key lipid metabolites.
Asunto(s)
Antiinflamatorios/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Colon/efectos de los fármacos , Ácidos Grasos Omega-3/uso terapéutico , Mucosa Intestinal/efectos de los fármacos , Animales , Antiinflamatorios/administración & dosificación , Colitis Ulcerosa/patología , Colon/ultraestructura , Sulfato de Dextran , Suplementos Dietéticos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Ácidos Grasos Omega-3/administración & dosificación , Aceites de Pescado/administración & dosificación , Aceites de Pescado/uso terapéutico , Mucosa Intestinal/ultraestructura , Masculino , Ratones Endogámicos BALB CRESUMEN
AIM: To investigate the underlying effect of Jianpi Qingchang decoction (JQD) regulating intestinal motility of dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: C57BL/6 mice were randomly divided into four groups: the control group, the DSS group, the JQD group, and the 5-aminosalicylic acid group. Except for the control group, colitis was induced in other groups by giving distilled water containing 5% DSS. Seven days after modeling, the mice were administered corresponding drugs intragastrically. The mice were sacrificed on the 15th day. The disease activity index, macroscopic and histopathologic lesions, and ultrastructure of colon interstitial cells of Cajal (ICC) were observed. The levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-10 and interferon gamma (IFN-γ), the expression of nuclear factor-kappa B (NF-κB) p65, c-kit, microtubule-associated protein 1 light chain 3 (LC3-II) and Beclin-l mRNA, and the colonic smooth muscle tension were assessed. RESULTS: Acute inflammation occurred in the mice administered DSS. Compared with the control group, the levels of IL-1ß, TNF-α, IL-10 and IFN-γ, the expression of LC3-II, Beclin-1 and NF-κB p65 mRNA, and the contractile frequency increased (P < 0.05), the expression of c-kit mRNA and the colonic smooth muscle contractile amplitude decreased in the DSS group (P < 0.05). Compared with the DSS group, the levels of IL-10 and IFN-γ, the expression of c-kit mRNA, and the colonic smooth muscle contractile amplitude increased (P < 0.05), the levels of TNF-α and IL-1ß, the expression of LC3-II, Beclin-1 and NF-κB p65 mRNA, and the contractile frequency decreased in the JQD group (P < 0.05). CONCLUSION: JQD can regulate the intestinal motility of DSS-induced colitis in mice through suppressing intestinal inflammatory cascade reaction, reducing autophagy of ICC, and regulating the network path of ICC/smooth muscle cells.
Asunto(s)
Autofagia/efectos de los fármacos , Colitis/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Motilidad Gastrointestinal/efectos de los fármacos , Células Intersticiales de Cajal/efectos de los fármacos , Animales , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/patología , Colon/efectos de los fármacos , Colon/metabolismo , Colon/ultraestructura , Sulfato de Dextran , Evaluación Preclínica de Medicamentos , Medicamentos Herbarios Chinos/farmacología , Masculino , Ratones Endogámicos C57BL , Fitoterapia , Distribución Aleatoria , Índice de Severidad de la EnfermedadRESUMEN
AIM: To investigate the effects of Ground Cherry (Physalis angulata L.) standardized supercritical CO2 extract in trinitrobenzenesulphonic acid (TNBS) model of rat intestinal inflammation. METHODS: The animals were divided into groups that received vehicle or P. angulata extract (PACO2) orally at the doses 25, 50 and 100 mg/kg daily by 5 d before TNBS damage. Protective effects of PACO2 were assessed by macroscopic analysis, biochemical determinations of the levels of myeloperoxidase (MPO), alkaline phosphatase (ALP), glutathione and cytokines (such as INF-γ, IL-1ß, IL-6, IL-10 and TNF-α), gene expression evaluation (including Hsp70, heparanase, NF-κB, mitogen-activated protein kinases (Mapk) 1, 3, 6 and 9, and the mucins genes Muc 1, 2, 3 and 4) and histopathological studies using optical, and electronic (transmission and scanning) microscopy. RESULTS: PACO2 extract promoted a significant reduction in MPO and ALP activities, reducing oxidative stress and neutrophil infiltration. These effects were accompanied by significant reduction of colonic levels of IFN-γ and IL-6 and down-regulation of heparanase, Hsp70, Mapk3, Mapk9, Muc1 and Muc2 genes expression when compared with TNBS-control animals. In addition, protective effects were also evidenced by reduced neutrophil infiltration, recovery of cell architecture and replacement of mucin by histopathological and ultrastructural analysis. CONCLUSION: Physalis angulata supercritical CO2 extract is an intestinal anti-inflammatory product that modulates oxidative stress, immune response and expression of inflammatory mediators, with potentially utility for treating inflammatory bowel disease.
Asunto(s)
Antiinflamatorios/uso terapéutico , Colitis/tratamiento farmacológico , Physalis/química , Extractos Vegetales/uso terapéutico , Administración Oral , Fosfatasa Alcalina/metabolismo , Animales , Dióxido de Carbono/química , Cromatografía con Fluido Supercrítico , Colitis/inducido químicamente , Colitis/patología , Colon/enzimología , Colon/patología , Colon/ultraestructura , Citocinas/metabolismo , Modelos Animales de Enfermedad , Regulación hacia Abajo , Mucosa Intestinal/enzimología , Mucosa Intestinal/patología , Mucosa Intestinal/ultraestructura , Masculino , Microscopía Electrónica de Transmisión de Rastreo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Infiltración Neutrófila/efectos de los fármacos , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Ácido Trinitrobencenosulfónico/toxicidadRESUMEN
AIM: To develop a new rat model we wanted to gain a better understanding of stricture formation in Crohn's disease (CD). METHODS: Chronic colitis was induced locally by the administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS). The relapsing inflammation characteristic to CD was mimicked by repeated TNBS treatments. Animals were randomly divided into control, once, twice and three times TNBS-treated groups. Control animals received an enema of saline. Tissue samples were taken from the strictured colonic segments and also adjacent proximally and distally to its 60, 90 or 120 d after the last TNBS or saline administrations. The frequency and macroscopic extent of the strictures were measured on digital photographs. The structural features of strictured gut wall were studied by light- and electron microscopy. Inflammation related alterations in TGF-beta 2 and 3, matrix metalloproteinases 9 (MMP9) and TIMP1 mRNA and protein expression were determined by quantitative real-time PCR and western blot analysis. The quantitative distribution of caspase 9 was determined by post-embedding immunohistochemistry. RESULTS: Intestinal strictures first appeared 60 d after TNBS treatments and the frequency of them increased up to day 120. From day 90 an intact lamina epithelialis, reversible thickening of lamina muscularis mucosae and irreversible thickening of the muscularis externa were demonstrated in the strictured colonic segments. Nevertheless the morphological signs of apoptosis were frequently seen and excess extracellular matrix deposition was recorded between smooth muscle cells (SMCs). Enhanced caspase 9 expression on day 90 in the SMCs and on day 120 also in myenteric neurons indicated the induction of apoptosis. The mRNA expression profile of TGF-betas after repeated TNBS doses was characteristic to CD, TGF-beta 2, but not TGF-beta 3 was up-regulated. Overexpression of MMP9 and down-regulation of TIMP1 were demonstrated. The progressive increase in the amount of MMP9 protein in the strictures was also obvious between days 90 and 120 but TIMP1 protein was practically undetectable at this time. CONCLUSION: These findings indicate that aligned structural and molecular changes in the gut wall rather than neuronal cell death play the primary role in stricture formation.
Asunto(s)
Colitis/patología , Colon/ultraestructura , Enfermedad de Crohn/patología , Obstrucción Intestinal/patología , Animales , Apoptosis , Western Blotting , Colitis/inducido químicamente , Colitis/genética , Colitis/metabolismo , Colon/metabolismo , Constricción Patológica , Enfermedad de Crohn/inducido químicamente , Enfermedad de Crohn/genética , Enfermedad de Crohn/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Inmunohistoquímica , Obstrucción Intestinal/genética , Obstrucción Intestinal/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Microscopía Electrónica de Transmisión , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Tiempo , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Factor de Crecimiento Transformador beta2/genética , Factor de Crecimiento Transformador beta2/metabolismo , Factor de Crecimiento Transformador beta3/genética , Factor de Crecimiento Transformador beta3/metabolismo , Ácido TrinitrobencenosulfónicoRESUMEN
AIM: To examine the effect of aqueous fructus aurantii immaturus (FAI) extracts on the intestinal plexus of cathartic colons. METHODS: Cathartic colons were induced in rats with dahuang, a laxative used in traditional Chinese medicine. Once the model was established (after approximately 12 wk), rats were administered mosapride (1.54 mg/kg) or various doses of aqueous FAI extracts (1-4 g/kg) for 14 d. Transit function was assessed using an ink propulsion test. Rats were then sacrificed, and the ultramicrostructure of colonic tissue was examined using transmission electron microscopy. The expression of the 5-hydroxytryptamine receptor 4 (5-HTR4) and neurofilament-H was assessed in colon tissues using real-time PCR, Western blot, and immunohistochemistry. RESULTS: Mosapride and high dose (4 g/kg) of aqueous FAI extracts significantly improved the bowel movement in cathartic colons compared to untreated model colons as measured by the intestinal transit rate (70.06 ± 7.25 and 72.02 ± 8.74, respectively, vs 64.12 ± 5.19; P < 0.05 for both). Compared to controls, the ultramicrostructure of cathartic colons showed signs of neural degeneration. Treatment with mosapride and aqueous FAI extracts resulted in recovery of ultrastructural pathology. Treatment with mosapride alone upregulated the gene and protein expression of 5-HTR4 compared to untreated controls (P < 0.05 for both). Treatment with aqueous FAI extracts (≥ 2 g/kg) increased 5-HTR4 mRNA levels (P < 0.05), but no change in protein level was observed by Western blot or immunohistochemistry. The mRNA and protein levels of neurofilament-H were significantly increased with mosapride and ≥ 2 g/kg aqueous FAI extracts compared to controls (P < 0.05 for all). CONCLUSION: Aqueous FAI extracts and mosapride strengthen bowel movement in cathartic colons via increasing the expression of 5-HTR4 and neurofilament-H.
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Catárticos/farmacología , Colon/efectos de los fármacos , Colon/inervación , Estreñimiento/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Motilidad Gastrointestinal/efectos de los fármacos , Plexo Mientérico/efectos de los fármacos , Animales , Benzamidas/farmacología , Colon/metabolismo , Colon/ultraestructura , Estreñimiento/patología , Estreñimiento/fisiopatología , Defecación/efectos de los fármacos , Modelos Animales de Enfermedad , Masculino , Morfolinas/farmacología , Plexo Mientérico/metabolismo , Plexo Mientérico/fisiopatología , Plexo Mientérico/ultraestructura , Degeneración Nerviosa , Proteínas de Neurofilamentos/genética , Proteínas de Neurofilamentos/metabolismo , Fitoterapia , Plantas Medicinales , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Receptores de Serotonina 5-HT4/genética , Receptores de Serotonina 5-HT4/metabolismo , Factores de Tiempo , Regulación hacia ArribaRESUMEN
OBJECTIVE: The aim of the present study was to study the modulatory potential of Azadirta indica on colonic surface abnormalities and membrane fluidity changes following 1,2 dimethylhydrazine-induced [DMH] colon carcinogenesis. MATERIALS AND METHODS: Brush border membranes [BBM] were isolated from the colon of rats and the viscosity as well as fluidity parameters were assessed by using the membrane extrinsic fluorophore pyrene. RESULTS: DMH treatment resulted in a significant increase in lipid peroxidation [LPO]. Reduced glutathione levels [GSH] and the activities of glutathione reductase [GR], glutathione transferase [GST], superoxide dismutase [SOD], catalase [CAT] and glutathione peroxidase [GPx] were found to be significantly decreased following DMH treatment. On the other hand, supplementation with AI, DMH-treated rats resulted in a significant decrease in the levels of lipid peroxidation but caused a significant increase in the levels of GSH as well in the activities of GR, GST, SOD, CAT and GPx. The results further demonstrated a marked decrease in membrane microviscosity following DMH treatment. On the other hand, a significant increase was observed in the excimer/monomer ratio and fluidity parameter of DMH-treated rats when compared to normal control rats. However, the alterations in membrane microviscosity and the fluidity parameters were significantly restored following A. indica treatment. Further, histological as well as colon surface alterations were also observed following DMH treatment, which however were greatly prevented upon AI co-administration. CONCLUSIONS: The study, therefore, concludes that A. indica proves to be useful in modulating the colonic surface abnormalities and membrane stability following DMH-induced colon carcinogenesis.
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Adenocarcinoma/prevención & control , Anticarcinógenos/uso terapéutico , Azadirachta , Colon/efectos de los fármacos , Neoplasias Colorrectales/prevención & control , Mucosa Intestinal/efectos de los fármacos , Fluidez de la Membrana/efectos de los fármacos , Fitoterapia , Extractos Vegetales/uso terapéutico , 1,2-Dimetilhidrazina , Adenocarcinoma/inducido químicamente , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Administración Oral , Animales , Anticarcinógenos/administración & dosificación , Catalasa/análisis , Colon/química , Colon/ultraestructura , Neoplasias Colorrectales/inducido químicamente , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Ensayos de Selección de Medicamentos Antitumorales , Glutatión/análisis , Glutatión Peroxidasa/análisis , Glutatión Reductasa/análisis , Peroxidación de Lípido/efectos de los fármacos , Masculino , Microscopía Electrónica de Rastreo , Microvellosidades/efectos de los fármacos , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/administración & dosificación , Hojas de la Planta , Distribución Aleatoria , Ratas , Ratas Wistar , Superóxido Dismutasa/análisis , Propiedades de SuperficieRESUMEN
Inflammatory bowel disease (IBD) is a chronic, relapsing, idiopathic inflammation of the gastrointestinal tract. Clinical studies suggest that the initiation of IBD is multifactorial, involving genetics, the immune system and environmental factors, such as diet, drugs and stress. Pfaffia paniculata is an adaptogenic medicinal plant used in Brazilian folk medicine as an "anti-stress" agent. Thus, we hypothesised that the P. paniculata enhances the response of animals subjected to colonic inflammation. Our aim was to investigate the intestinal anti-inflammatory activity of P. paniculata in rats before or after induction of intestinal inflammation using trinitrobenzenesulfonic acid (TNBS). The animals were divided into groups that received the vehicle, prednisolone or P. paniculata extract daily starting 14 days before or 7 days after TNBS induction. At the end of the procedure, the animals were killed and their colons were assessed for the macroscopic damage score (MDS), extent of the lesion (EL) and weight/length ratio, myeloperoxidase (MPO) activity and glutathione (GSH), cytokines and C-reactive protein (CRP) levels. Histological evaluation and ultrastructural analysis of the colonic samples were performed. Treatment with the 200mg/kg dose on the curative schedule was able to reduce the MDS and the EL. In addition, MPO activity was reduced, GSH levels were maintained, and the levels of pro-inflammatory cytokines and CRP were decreased. In conclusion, the protective effect of P. paniculata was related to reduced oxidative stress and CRP colonic levels, and due to immunomodulatory activity as evidenced by reduced levels of IL-1ß, INF-γ, TNF-α and IL-6.
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Antiinflamatorios/uso terapéutico , Colitis/tratamiento farmacológico , Panax , Extractos Vegetales/uso terapéutico , Animales , Antiinflamatorios/farmacología , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/patología , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Colon/ultraestructura , Citocinas/metabolismo , Glutatión/metabolismo , Masculino , Microscopía Electrónica de Rastreo , Peroxidasa/metabolismo , Fitoterapia , Extractos Vegetales/farmacología , Ratas Wistar , Ácido TrinitrobencenosulfónicoRESUMEN
AIM: The herbal prescription Chang'an II is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome (IBS). In this study we investigated the effects of Chang'an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS (PI-IBS) model. METHODS: A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang'an II (2.85, 5.71 and 11.42 g · kg(-1) · d(-1), ig) for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex (AWR) scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4(+) and CD8(+) cells were counted and IL-1ß and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. RESULTS: PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang'an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang'an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4(+)/CD8(+) cell ratio in lamina propria and submucosa, and increased IL-1ß and reduced IL-4 expression in intestinal mucosa, whereas Chang'an II treatment reversed PI-IBS-induced changes in CD4(+)/CD8(+) cell ratio and expression of IL-1ß and IL-4. CONCLUSION: Chang'an II treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.
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Antiinflamatorios/farmacología , Colitis/tratamiento farmacológico , Colon/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Fármacos Gastrointestinales/farmacología , Mucosa Intestinal/efectos de los fármacos , Síndrome del Colon Irritable/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Animales , Animales Recién Nacidos , Conducta Animal/efectos de los fármacos , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Colitis/inducido químicamente , Colitis/inmunología , Colitis/metabolismo , Colitis/patología , Colitis/psicología , Colon/inmunología , Colon/metabolismo , Colon/ultraestructura , Modelos Animales de Enfermedad , Combinación de Medicamentos , Heces/química , Conducta Alimentaria/efectos de los fármacos , Preferencias Alimentarias/efectos de los fármacos , Inmunidad Mucosa/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Interleucina-1beta/metabolismo , Interleucina-4/metabolismo , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/ultraestructura , Síndrome del Colon Irritable/inducido químicamente , Síndrome del Colon Irritable/inmunología , Síndrome del Colon Irritable/metabolismo , Síndrome del Colon Irritable/patología , Síndrome del Colon Irritable/psicología , Masculino , Medicina Tradicional China , Actividad Motora/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Ratas Sprague-Dawley , Ácido TrinitrobencenosulfónicoRESUMEN
The present study explored the regulatory role of zinc on the in vitro uptake of ¹4C-glucose and ¹4C-labeled amino acids and on colonic surface abnormalities after 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Rats were segregated into four groups: control, DMH-treated, zinc-treated, and DMH + zinc-treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 16 weeks. Zinc (in the form of zinc sulfate) was given to rats at a dose level of 227 mg/L in their drinking water. DMH treatment caused a significant decrease in the activities of disaccharidases (sucrase, lactase, and maltase), but a significant increase in the activity of alkaline phosphatase. In vitro uptake of ¹4C-D-glucose and the amino acids ¹4C-glycine, ¹4C-alanine, ¹4C-lysine, and ¹4C-leucine were significantly higher in the colons of DMH-treated rats. Zinc supplementation of DMH-treated rats resulted in regulating the altered intestinal enzyme activities and in vitro uptake of ¹4C-amino acids and ¹4C-glucose. Scanning electron microscopy revealed drastic alterations in the colon surface morphology after DMH treatment, which were restored after zinc supplementation. Our results confirm a beneficial effect of zinc against DMH-induced alterations in the colons of rats.
Asunto(s)
1,2-Dimetilhidrazina/farmacología , Aminoácidos/metabolismo , Anticarcinógenos/uso terapéutico , Colon/ultraestructura , Neoplasias del Colon/prevención & control , Sulfato de Zinc/uso terapéutico , Fosfatasa Alcalina/metabolismo , Animales , Anticarcinógenos/administración & dosificación , Radioisótopos de Carbono , Colon/efectos de los fármacos , Colon/enzimología , Colon/metabolismo , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Disacaridasas/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/enzimología , Mucosa Intestinal/ultraestructura , Masculino , Microscopía Electrónica de Rastreo , Ratas , Ratas Sprague-Dawley , Zinc/metabolismo , Sulfato de Zinc/administración & dosificaciónRESUMEN
OBJECTIVE: To investigate the effect of total alkaloids of Sophora alopecuroides (TASA) on dextran sulfate sodium (DSS)-induced colitis in mice. METHODS: Chronic experimental colitis was induced by administration of 4 cycles of 4% DSS. Fifty mice were randomly distributed into 4 groups (normal, DSS, DSS/high-dose TASA, and DSS/low-dose TASA groups) by a random number table with body weight stratification. Mice in the normal group (n=11) and DSS-induced colitis control group (n=15) received control treatment of 20 mL/kg distilled water; DSS plus TASA high- and low-dose groups (n=12 each) were treated with TASA solution (20 mL/kg) at the doses of 60 mg/kg and 30 mg/kg, respectively. The severity of colitis was assessed on the basis of clinical signs, colon length, and histology scores. Moreover, secretory immunoglobulin A (sIgA) and haptoglobin (HP) were analyzed by enzyme linked immunosorbent assay; intercellular adhesion molecule 1 (ICAM-1) and macrophage-migration inhibitory factor (MIF) gene expressions were analyzed by quantitative reverse transcriptase realtime polymerase chain reaction (qRT-PCR) using SYBA green I; and nuclear factor κ B (NF-κ B) expression and activation and p65 interaction with the promoter of ICAM-1 gene were assessed by Western blotting and chromatin immunoprecipitation assay. RESULTS: TASA administration significantly attenuated the damage and substantially reduced HP elevation and maintained the level of cecum sIgA. TASA inhibited the ICAM-1 gene expression and had no effect on MIF gene expression. Also, TASA was able to reduce phospho-I κ B α (p-I κ B α) protein expression; however, it had no effect on the activation of I κ B kinase α (IKK α) and inhibitor of NF-κ B α (I κ B α). Moreover, TASA inhibited the p65 recruitment to the ICAM-1 gene promoter. CONCLUSIONS: TASA had a protective effect on DSS-induced colitis. Such effect may be associated with its inhibition of NF-κ B activation and blockade of NF-κ B-regulated transcription activation of proinflammatory mediator gene.
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Alcaloides/uso terapéutico , Colitis/tratamiento farmacológico , Colitis/prevención & control , Sustancias Protectoras/uso terapéutico , Sophora/química , Alcaloides/farmacología , Animales , Ciego/efectos de los fármacos , Ciego/metabolismo , Ciego/patología , Colitis/inducido químicamente , Colitis/patología , Colon/patología , Colon/ultraestructura , Sulfato de Dextran , Regulación hacia Abajo/efectos de los fármacos , Femenino , Haptoglobinas/metabolismo , Proteínas I-kappa B/metabolismo , Inmunoglobulina A Secretora/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Mucosa Intestinal/ultraestructura , Factores Inhibidores de la Migración de Macrófagos/genética , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Inhibidor NF-kappaB alfa , Fosforilación/efectos de los fármacos , Fitoterapia , Regiones Promotoras Genéticas/genética , Sustancias Protectoras/farmacología , Unión Proteica/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Factor de Transcripción ReIA/metabolismoRESUMEN
OBJECTIVE: To explore the significance of colonic epithelial cell apoptosis and tumor necrosis factor α (TNF-α) changing in pathogenesis of melanosis coli (MC) in guinea pig and the molecular mechanism of rhubarb (Rhu) in inducing the disease, by means of using different dosages of Rhu to induce the disease. METHODS: One hundred and forty-four male guinea pigs, clean grade, were randomized according to their body weight into 5 groups, the untreated normal group and the 4 Rhu groups treated, respectively, with different doses of Rhu, 3 g/kg·d for low dose (Rhu-l) group, 6 g/kg·d for moderate dose (Rhu-m) group, 12 g/kg·d for high dose (Rhu-h) group and 24 g/kg·d for super-high dose (Rhu-s) group via gastric infusion. All animals were sacrificed 60 days later, their viscera were taken for observing the pathologic and morphologic changes with HE, melanin and melatonin staining, and the apoptosis of colonic epithelial cells was detected with TUNEL stain and transmission electric microscopy. In addition, the levels of TNF-α in serum and colonic tissue were measured using ELISA and RT-PCR. RESULTS: The pathological changes of MC could be found by naked eye in all Rhu groups, especially apparent at caecum and proximal end of colon, but did not found in gallbladder, jejunum and ileum. In normal guinea pigs, the colonic membrane was pink in color with no apparent pigment deposition. Membranous color deepened in the Rhu groups depending on the dosage of Rhu used. MC scoring showed the highest scores revealed in the Rhu-s group (6.00±0.00), which was significantly different to those in the Rhu-l (3.86±0.69), Rhu-m (4.43±0.79) and Rhu-h groups (4.88±0.35, all P<0.05). Levels of cell apoptosis in colon and TNF-α in serum in all Rhu groups were higher than those in the normal group (P<0.01), but showed no significant difference among the Rhu groups (P>0.05). Moreover, a positive correlation was found in the degree of induced MC with apoptosis rate and TNF-α level. CONCLUSIONS: Rhu (anthraquinone purgatives) had apparent effect on inducing MC; its molecular mechanism is maybe to destroy intestinal mucosal barrier and advance proinflammatory factor TNF-α releasing, which leads to colonic epithelial cells apoptosis, and finally induce the change of MC due to the deposition of brown pigments, i.e. the macrophage phagocytized apoptotic body, on the colonic membrane.
Asunto(s)
Antraquinonas/efectos adversos , Catárticos/efectos adversos , Enfermedades del Colon/inducido químicamente , Enfermedades del Colon/patología , Melanosis/inducido químicamente , Melanosis/patología , Animales , Apoptosis/efectos de los fármacos , Colon/patología , Colon/ultraestructura , Enfermedades del Colon/sangre , Enfermedades del Colon/complicaciones , Células Epiteliales/efectos de los fármacos , Células Epiteliales/patología , Regulación de la Expresión Génica/efectos de los fármacos , Cobayas , Etiquetado Corte-Fin in Situ , Masculino , Melanosis/sangre , Melanosis/complicaciones , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
The present study evaluated the modulatory effects of zinc on 1,2-dimethylhydrazine (DMH)-induced ultrastructural changes in rat colon as well as on [(3)H]thymidine uptake and [(14)C]D-glucose metabolism. The rats were segregated into four groups: normal control, DMH treated, zinc treated, DMH + zinc treated. Initiation and induction of colon carcinogenesis was achieved through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 and 16 weeks, respectively. Zinc was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum for two different time durations of 8 and 16 weeks. The study revealed a significant decrease in zinc concentration in serum and colon following DMH treatment to rats, which upon zinc supplementation were recovered to near normal levels. A significant increase in in vitro [(3)H]thymidine uptake was observed following 16 weeks of DMH treatment. Further, a significant increase in the [(14)C]glucose turnover was observed following 8 and 16 weeks of DMH treatment. Simultaneous supplementation of zinc to DMH-treated rats for 16 weeks significantly decreased the uptake of [(3)H]thymidine and [(4)C]glucose when compared to DMH alone-treated rats. Changes in the ultrastructural architecture of colonic cells were evident following both treatment schedules of DMH; however, the changes were more distinguishable following 16 weeks of DMH treatment. The most obvious changes were seen in nuclear shape and disruption of cellular integrity, which upon zinc supplementation was appreciably improved. In conclusion, the study suggests positive beneficial effect of zinc against chemically induced colonic preneoplastic progression in rats.
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1,2-Dimetilhidrazina/toxicidad , Colon/efectos de los fármacos , Neoplasias del Colon/ultraestructura , Zinc/farmacología , Animales , Colon/ultraestructura , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/prevención & control , Glucosa/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Timidina/metabolismo , Zinc/sangreRESUMEN
The present study evaluated the modulatory effects of zinc on colonic membrane fluidity and surface abnormalities following 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis. Rats were segregated into four groups: normal control, DMH treated, zinc treated, DMH + zinc treated. Colon carcinogenesis was initiated through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 weeks. Zinc (in the form of zinc sulphate) was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum, for the entire duration of the study. Brush border membranes (BBM) were isolated from the colon of rats and the fluidity parameters were assessed by steady-state fluorescence polarization technique using the membrane extrinsic fluorophore 1,6-diphenyl-1,3,5-hexatriene (DPH). The translational diffusion was measured by using the excimer formation of pyrene incorporated in the membrane. The results demonstrated a significant increase in the polarization and anisotropy, accompanied by an increase in order parameter in the membrane preparations from the colon of DMH-injected rats. Further, studies with pyrene fluorophore indicated a marked decrease in membrane microviscosity following DMH treatment. However, the alterations in membrane fluorescence polarization and the fluidity parameters were completely restored following zinc treatment. Drastic alterations in colon surface were noticed after 8 weeks of DMH treatment. However, zinc treatment to DMH-treated rats greatly restored normalcy in the colonic surface. The study concludes that zinc has a strong membrane stabilizing effect and thus has a positive beneficial effect against chemically induced colonic preneoplastic progression in rats.
Asunto(s)
1,2-Dimetilhidrazina/farmacología , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/patología , Fluidez de la Membrana/efectos de los fármacos , Microvellosidades/efectos de los fármacos , Zinc/farmacología , Animales , Peso Corporal/efectos de los fármacos , Colon/efectos de los fármacos , Colon/patología , Colon/ultraestructura , Difenilhexatrieno/química , Polarización de Fluorescencia , Masculino , Microscopía Electrónica de Rastreo , Microvellosidades/química , Pirenos/química , Ratas , Ratas Wistar , Propiedades de Superficie/efectos de los fármacos , Viscosidad/efectos de los fármacos , Zinc/sangreRESUMEN
Human intervention studies have suggested an exciting synergistic action between calcium supplementation and aspirin intake in reducing the risk of colorectal cancer. The aim of this study was to determine whether such a synergy can be demonstrated on azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) formation in mice and rats. Female CF-1 mice and male F344 rats were injected subcutaneously with AOM and then received diet treatments for 8 wk. The basal control diet contained high fat (20% mixed lipids by weight) and low calcium (1.4 mg/g diet) to mimic the average Western diet. The treatment diets contained enriched calcium (5.2 mg calcium/g diet), aspirin (0.2 mg aspirin/g diet), or calcium plus aspirin (5.2 mg calcium plus 0.2 mg aspirin/g diet). Treatment with calcium, aspirin, or their combination significantly decreased the number of total ACF and aberrant crypt per mouse (by 43-59%) or rat (by 23-38%), but statistically significant differences among the 3 groups were not observed. A hint of additivity between calcium and aspirin was observed in mice but not in rats. These results indicate that the combination of calcium and aspirin did not produce a synergistic effect on the ACF formation in AOM-treated mice and rats.