Sericin as treatment of obesity: morphophysiological effects in obese mice fed with high-fat diet / Sericina como tratamento da obesidade: efeitos morfofisiológicos de camundongos obesos por dieta hiperlipídica

ABSTRACT Objective To investigate the effects of sericin extracted from silkworm Bombyx mori cocoon on morphophysiological parameters in mice with obesity induced by high-fat diet. Methods Male C57Bl6 mice aged 9 weeks were allocated to one of two groups - Control and Obese, and fed a standard or high-fat diet for 10 weeks, respectively. Mice were then further subdivided into four groups with seven mice each, as follows: Control, Control-Sericin, Obese, and Obese-Sericin. The standard or high fat diet was given for 4 more weeks; sericin (1,000mg/kg body weight) was given orally to mice in the Control-Sericin and Obese-Sericin Groups during this period. Weight gain, food intake, fecal weight, fecal lipid content, gut motility and glucose tolerance were monitored. At the end of experimental period, plasma was collected for biochemical analysis. Samples of white adipose tissue, liver and jejunum were collected and processed for light microscopy analysis; liver fragments were used for lipid content determination. Results Obese mice experienced significantly greater weight gain and fat accumulation and had higher total cholesterol and glucose levels compared to controls. Retroperitoneal and periepididymal adipocyte hypertrophy, development of hepatic steatosis, increased cholesterol and triglyceride levels and morphometric changes in the jejunal wall were observed. Conclusion Physiological changes induced by obesity were not fully reverted by sericin; however, sericin treatment restored jejunal morphometry and increased lipid excretion in feces in obese mice, suggesting potential anti-obesity effects.

RESUMO Objetivo Investigar os efeitos da sericina extraída de casulos de Bombyx mori na morfofisiologia de camundongos com obesidade induzida por dieta hiperlipídica. Métodos Camundongos machos C57Bl6, com 9 semanas de idade, foram distribuídos em Grupos Controle e Obeso, que receberam ração padrão para roedores ou dieta hiperlipídica por 10 semanas, respectivamente. Posteriormente, os animais foram redistribuídos em quatro grupos, com sete animais cada: Controle, Controle-Sericina, Obeso e Obeso-Sericina. Os animais permaneceram recebendo ração padrão ou hiperlipídica por 4 semanas, período no qual a sericina foi administrada oralmente na dose de 1.000mg/kg de massa corporal aos Grupos Controle-Sericina e Obeso-Sericina. Parâmetros fisiológicos, como ganho de peso, consumo alimentar, peso das fezes em análise de lipídios fecais, motilidade intestinal e tolerância à glicose foram monitorados. Ao término do experimento, o plasma foi coletado para dosagens bioquímicas e fragmentos de tecido adiposo branco; fígado e jejuno foram processados para análises histológicas, e amostras hepáticas foram usadas para determinação lipídica. Resultados Camundongos obesos apresentaram ganho de peso e acúmulo de gordura significativamente maior que os controles, aumento do colesterol total e glicemia. Houve hipertrofia dos adipócitos retroperitoneais e periepididimais, instalação de esteatose e aumento do colesterol e triglicerídeos hepáticos, bem como alteração morfométrica da parede jejunal. Conclusão O tratamento com sericina não reverteu todas as alterações fisiológicas promovidas pela obesidade, mas restaurou a morfometria jejunal e aumentou a quantidade de lipídios eliminados nas fezes dos camundongos obesos, apresentando-se como potencial tratamento para a obesidade.

Effects of anti-TNF-α in experimental diversion colitis

Abstract Purpose: To evaluate the effects of infliximab on the inflammation of the colonic mucosa devoid from fecal stream. Methods: Twenty-four rats were submitted to a Hartmann's procedure. They remained for 12 weeks with the fecal derivation to development of diversion colitis on excluded colorectal stump. After this period, they were divided into 3 groups: one group received intervention with saline (2.0 mL / week), other group infliximab at doses of 5 mg/kg/week and the other 10 mg/kg/week for five consecutively weeks. Concluded the intervention period, the animals were euthanized to remove colon segments with and without fecal stream. Colitis was diagnosed by histological analysis and the degree of inflammation by validated score. The neutrophilic infiltrate was evaluated by tissue expression of myeloperoxidase identified by immunohistochemical. The tissue content of myeloperoxidase was measured by computer-assisted image analysis. Results: The inflammatory score was high in colonic segments without fecal stream. The intervention with infliximab reduced the inflammatory score in excluded colonic segments. The content of myeloperoxidase was reduced in colonic segments of animals treated with infliximab mainly in high concentrations. Conclusion: Intervention with infliximab reduced the inflammation and the neutrophil infiltrate in colonic segments devoid of the fecal stream.

Efecto del endospermo de semilla de tara y polvo de hojas de Agave americana en el peso corporal y velocidad de tránsito intestinal en ratas / Effects of the endosperm of tara seeds and powder of Agave Americana leaves on body weight and intestinal transit time in holtzman rats

RESUMEN Objetivos. Evaluar el efecto del endospermo de semilla de tara (EST) y polvo de hojas del Agave americana (HAA) sobre el peso corporal y velocidad de tránsito intestinal en ratas Holtzman. Materiales y métodos Veinticinco ratas machos Holtzman distribuidas en cinco grupos y alojadas en jaulas individuales, fueron alimentadas durante 21 días con uno de los siguientes tratamientos: T1, dieta con 6% de alfa celulosa (control); T2, dieta con 6% de EST; T3, dieta con 6% de HAA; T4, dieta con 10% de EST y T5, dieta con 10% de HAA. Se registraron el consumo de alimento, ganancia de peso corporal, digestibilidad aparente de la grasa, características de las heces (contenido de grasa, peso, humedad, volumen y pH) y tiempo de tránsito intestinal. Se realizaron análisis de varianza (ANOVA) de una vía y a través de la comparación múltiple de medias de Tukey. Resultados Dietas con 6% y 10% del EST exhibieron una reducción en el consumo de alimento, digestibilidad aparente de la grasa y pH fecal, cuyos resultados tuvieron efectos en la reducción de la ganancia del peso corporal de 37,0% (p=0,008) y 50,9% (p=0,001) comparados con la dieta control. Dieta con 10% del polvo de HAA redujo el tiempo de tránsito intestinal de 642 min (control) a 532 min (p=0,242). Conclusiones Dietas que contienen EST regulan la ganancia del peso corporal; en cambio, dieta con polvo de HAA, no tuvo efectos sobre la velocidad de tránsito intestinal en ratas.

ABSTRACT Objective To evaluate the effects of endosperm of tara seeds (ETS) and powder of Agave americana leaves (AAL) on body weight and intestinal transit time in Holtzman rats. Materials and Methods Twenty-five male Holtzman rats, individually caged, and distributed into five groups were fed for 21 days with one of the following treatments: T1, diet with 6% alpha cellulose (Control); T2, diet with 6% ETS; T3, diet with 6% AAL; T4, diet with 10% ETS; and T5, Diet with 10% AAL. Feed intake, body weight gain, apparent digestibility of fat, characteristics of feces (fat content, weight, moisture, volume, and pH) and intestinal transit time were recorded. One-way analyses of variance (ANOVA) were performed, as well as Tukey's multiple means comparison. Results Diets with 6% and 10% of ETS resulted in a reduction of feed intake, apparent digestibility of fat, and fecal pH, and said results had an effect in the reduction of body weight gain of 37.0% (p=0.008) and 50.9% (0.001), compared with the control diet. The diet with 10% of AAL powder reduced the intestinal transit time from 642 min (control) to 532 min (p=0.242). Conclusions Diets containing EST regulated body weight gain, while the diet with AAL powder had no effects on the intestinal transit time in rats.

Effect of bisacodyl on rats with slow transit constipation

The effect of bisacodyl on the treatment of rats with slow transit constipation (STC) was studied. Forty-five female Wister rats were divided into control group, STC group, and STC bisacodyl group. The immunohistochemical method was used to determine interstitial cells of Cajal (ICC) and the expression of c-Kit protein. Body mass and the number of defecations were significantly decreased in the STC group compared with the control group on the 100th day after diphenoxylate administration, while dry weight of feces was significantly increased and the intestinal transit time was prolonged. There were significant differences in the number of defecations, dry weight of feces, and intestinal transit time among the three groups. The number of defecations was higher, dry weight of feces was lower, and intestinal transit time was shorter in the STC bisacodyl group compared to the STC group. In addition, ICC basement membrane dissolution occurred in the colon wall of the STC group. The connection between ICC and surrounding cells was destroyed, and the nucleus shrunken to different degrees. Moreover, c-Kit expression in the STC group was significantly lower than the control group. The connection between ICC and surrounding cells in the STC bisacodyl group was significantly stronger than the STC group, and the number of ICC and the expression of c-Kit were increased. Bisacodyl could reduce the severity of STC in rats by increasing the number of ICC and the expression of c-Kit.

Ethacrynic acid decreases expression of proinflammatory intestinal wall cytokines and ameliorates gastrointestinal stasis in murine postoperative ileus

OBJECTIVES: Several compounds characterized by an olefin linkage conjugated to a carbonyl group have anti-inflammatory properties. The diuretic ethacrynic acid (EA) is a compound of this type. Herein, we tested the hypothesis that ethacrynic acid can modulate the development of ileus after bowel manipulation. METHODS: Groups (n=9) of male C57Bl/6 mice underwent surgical manipulation of the small intestine using a pair of cotton-tipped applicators (MAN). Control animals (CONT) did not undergo any surgical intervention or receive treatment. MAN mice were pre- and post-treated with four intraperitoneal doses of phosphate buffered saline (PBS), EA1 (1mg/kg per dose), or EA10 (10mg/kg per dose). Gastrointestinal transit of non-absorbable FITC-labeled dextran was assessed by gavaging the mice with the tracer 24h after operation and assessing FD70 concentration 120 min later in the bowel contents from the stomach, 10 equally long segments of small intestine, cecum, and two equally long segments of colon. The geometric center for the tracer was calculated for each animal. Expression of interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) transcripts in the ileal muscularis propria was assessed using semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: In control animals, the mean (±SE) geometric center for the transit marker was 9.89±0.47, whereas it was 4.59±0.59 for PBS-treated animals (p<0.05 vs CONT). The geometric center for pre- post treatment with low (1mg/kg) and high (10mg/kg) doses of ethacrynic acid were 7.23±0.97 and 5.15±0.57, respectively. Compared to PBS, treatment with ethacrynic acid (1mg/kg) significantly decreased manipulation-induced IL-6 and iNOS mRNA expression in the wall of the small bowel. CONCLUSIONS: Pre- and post-treatment with ethacrynic acid ameliorates ileus and modulates inflammation in the gut wall induced by bowel manipulation.

Tissue sulfomucin and sialomucin content in colon mucosa without intestinal transit subjected to intervention with Curcuma longa (curcumin)

Abstract Purpose: To measure the tissue sulfomucin and sialomucin content of the colon mucosa without fecal flow, subjected to intervention with curcumin, and the influence of the concentration used and the intervention time. Methods: Thirty-six rats were subjected to proximal right colostomy and distal mucous fistula. They were divided into two groups according to whether sacrifice was performed two or four weeks after the intervention. Each group was divided into three subgroups according to the enema applied daily: saline alone; curcumin at 50 mg/kg/day or curcumin at 200 mg/kg/day. Acid mucins were diagnosed using the Alcian blue technique. The mucin content was quantified by means of computer-assisted image analysis. The significance level of 5% was used throughout (p < 0.05). Results: There were dose-related increases in the quantities of sulfomucins in the animals subjected to interventions with curcumin, both after two weeks (p < 0.00001) and after four weeks (p < 0.00001). There were increases in sialomucin quantity that were concentration-related (p < 0.00001) and time-related (p < 0.00001). Conclusion: Curcumin enemas increase the quantity of acid mucins in the intestinal flow in the excluded colon, with dose and time dependency.

Ramosetron might be useful for treating diabetic diarrhea with a rapid small bowel transit time

No abstract available.

Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats / Mucosite induzida pelo metotrexato retarda o esvaziamento gástrico e o trânsito gastrointestinal de líquidos em ratos acordados

CONTEXT: Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate. OBJECTIVES: To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced intestinal mucositis. METHODS: Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcutaneously) or saline. After 1, 3 and 7 days, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage and myeloperoxidase activity (biochemical marker of granulocyte infiltration). Others rats were pre-treated with methotrexate or saline, gavage-fed after 3 or 7 days with a standard test liquid meal, and sacrificed 10, 20 or 30-min later. Gastric and small intestine dye recoveries were measured by spectrophotometry. RESULTS: After 3 days of methotrexate, there was an epithelial intestinal damage in all segments, with myeloperoxidase activity increase in both in duodenum and ileum. Seven days after methotrexate, we observed a complete reversion of this intestinal damage. There was an increase in gastric dye recoveries after 10, 20, and 30-min post-prandial intervals after 3 days, but not after 7 days, of methotrexate. Intestine dye recoveries were decreased in the first and second segments at 10 min, in the third at 20 min, and in the second and third at 30 min, only after 3 days of methotrexate treatment. CONCLUSION: Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats.

CONTEXTO: Metotrexato e outros agentes anticâncer podem induzir uma mucosite intestinal, que é um dos fatores de limitante mais comum que limitam o aumento escalonado da dose do metotrexato. OBJETIVOS: Avaliar o esvaziamento gástrico e o trânsito gastrointestinal de líquidos na mucosite intestinal induzida por metotrexato. MÉTODOS: Ratos Wistar, receberam metotrexato (2.5 mg/kg/dia por 3 dias, subcutâneo) ou salina. Após 1, 3 ou 7 dias, secções do duodeno, jejuno e íleo foram retirados para análise morfométrica e dosagem da atividade de mieloperoxidase (marcador bioquímico da infiltração de neutrófilos). Outros ratos foram pré-tratados com metotrexato ou salina, após 3 ou 7 dias, foram alimentados mediante gavagem com uma refeição teste e sacrificados após 10, 20 e 30 minutos. As retenções fracionais do corante no estômago e em três segmentos do intestino delgado foram determinados por espectrofotometria. RESULTADOS: Após 3 dias do metotrexato, houve lesão do epitélio intestinal em todos os segmentos, com aumento da atividade de mieloperoxidase, no duodeno e íleo. Sete dias após o metotrexato, foi observada completa reversão da lesão intestinal. Observou-se ainda retardo no esvaziamento gástrico após 10 min, 20 min e 30 min, após 3 dias, mas não após 7 dias do tratamento com metotrexato. A retenção fracional dos segmentos do intestino foi reduzida no primeiro e segundo segmentos após 10 min, e no terceiro segmento após 30 min da administração da refeição, somente 3 dias após o tratamento com metotrexato. CONCLUSÃO: A mucosite intestinal induzida por metotrexato retarda o esvaziamento gástrico e o trânsito gastrointestinal de líquidos em ratos acordados.

Efeito do tratamento convencional da constipação crônica funcional no tempo de trânsito orocecal e colônico total e segmentar / Effects of conventional treatment of chronic functional constipation on total and segmental colonic and orocecal transit times

OBJETIVO: Avaliar o efeito do tratamento convencional da constipação crônica funcional no tempo de trânsito colônico total e segmentar e no tempo de trânsito orocecal. MÉTODOS: Foram incluídos 34 pacientes com constipação funcional atendidos consecutivamente em ambulatório especializado. O tempo de trânsito colônico total e segmentar foi avaliado com marcadores radiopacos. O tempo de trânsito orocecal da lactulose e do feijão foi avaliado com teste do hidrogênio no ar expirado. O tratamento constou de desimpactação, orientações gerais e de consumo de dieta rica em fibra alimentar e administração de óleo mineral. RESULTADOS: Na admissão, dismotilidade colônica foi encontrada em 71,9 por cento (23/32) dos pacientes. Todos os pacientes que realizaram corretamente o tratamento apresentaram melhora clínica na sexta semana do tratamento quando 82,6 por cento (19/23) daqueles com dismotilidade na admissão apresentaram normalização ou diminuição da gravidade no padrão de trânsito colônico. Observou-se redução do tempo de trânsito (medianas) entre a admissão e a oitava semana de tratamento: trânsito orocecal da lactulose (de 70 para 50 minutos, p = 0,002), orocecal do feijão (de 240 para 220 minutos, p = 0,002) e colônico total (de 69,5 para 37,0 horas, p = 0,001). A necessidade de uso de óleo mineral para controle da constipação aos 12 meses de tratamento associou-se com persistência de trânsito colônico total superior a 62 horas na oitava semana de tratamento (p = 0,014). CONCLUSÃO: O programa terapêutico convencional proporcionou bons resultados independentemente da presença ou não de dismotilidade colônica na admissão ao estudo. As anormalidades da motilidade digestiva na constipação funcional da criança podem apresentar reversibilidade e ser de natureza secundária.

OBJECTIVE: To evaluate the effects of conventional treatment of chronic functional constipation on total and segmental colonic transit times and on orocecal transit time. METHODS: A total of 34 consecutive patients with functional constipation attending a specialized outpatient clinic were included in the study. Total and segmental colonic transit times were assessed using radiopaque markers. Hydrogen breath test was used to evaluate lactulose and bean orocecal transit times. Treatment consisted of disimpaction, general and dietary fiber intake instruction, and mineral oil administration. RESULTS: At admission, colonic dysmotility was found in 71.9 percent (23/32) of patients. All patients who complied with the treatment showed improvement of clinical symptoms after 6 weeks of treatment, when 82.6 percent (19/23) of those with dysmotility at admission returned to normal or reduced the severity of colonic transit patterns. Transit time decreased (medians) between admission and eighth week of treatment: lactulose orocecal transit (from 70 to 50 minutes, p = 0.002), bean orocecal transit (from 240 to 220 minutes, p = 0.002), and total colonic transit (from 69.5 to 37.0 hours, p = 0.001). The need for mineral oil therapy for constipation after a 12-month treatment was associated with persistence of total colonic transit higher than 62 hours at the eighth week of treatment (p = 0.014). CONCLUSION: The conventional therapeutic approach yielded good results regardless of the presence or not of colonic dysmotility at inclusion in the study. Digestive tract motility abnormalities in functionally constipated children may be reversed, and may be secondary to constipation.

Vincristine delays gastric emptying and gastrointestinal transit of liquid in awake rats

We evaluated the effects of vincristine on the gastrointestinal (GI) motility of awake rats and correlated them with the course of vincristine-induced peripheral neuropathy. Vincristine or saline was injected into the tail vein of male Wistar rats (180-250 g) on alternate days: 50 µg/kg (5 doses, N = 10), 100 µg/kg (2, 3, 4 and 5 doses, N = 49) or 150 µg/kg (1, 2, or 5 doses, N = 37). Weight and stool output were measured daily for each animal. One day after completing the vincristine treatment, the animals were fasted for 24 h, gavage-fed with a test meal and sacrificed 10 min later to measure gastric emptying (GE), GI transit and colon weight. Sensory peripheral neuropathy was evaluated by hot plate testing. Chronic vincristine treatments with total cumulative doses of at least 250 µg/kg significantly decreased GE by 31-59 percent and GI transit by 55-93 percent. The effect of 5 doses of vincristine (150 µg/kg) on GE did not persist for more than 1 week. Colon weight increased after 2 and 5 doses of vincristine (150 µg/kg). Fecal output decreased up to 48 h after the fifth dose of vincristine (150 µg/kg). Vincristine decreased the heat pain threshold 1 day after 5 doses of 50-100 µg/kg or after 3-5 doses of 150 µg/kg. This effect lasted for at least 2 weeks after the fifth dose. Chronic intravenous vincristine treatment delayed GE and GI transit of liquid. This effect correlated with the peak increase in colon weight but not with the pain threshold changes.