Gastric plication surgery changes gastrointestinal and metabolic parameters in an obesity-induced high-fat diet model.

BACKGROUND: Obesity treatment includes less invasive procedures such as gastric plication (GP) surgery; however, its effects on gastrointestinal (GI) motility parameters are underestimated. We aimed to verify the metabolic and gastrointestinal effects of GP surgery in the rat obesity model. METHODS: A high-fat diet-induced obesity was used. Animals were allocated to four experimental groups: control sham (n = 6); control GP (n = 10); obese sham (n = 6); and obese GP (n = 10). Nutritional and murinometric parameters, gastric motility, glucose tolerance, histopathology, fat depots, leptin, and lipoproteins levels were evaluated 30 days after surgery. Data were analyzed by ANOVA followed by post Tukey or Kruskal-Wallis test followed by Dunn's multiple comparisons test. KEY RESULTS: Gastric plication decreased leptin levels, feed efficiency, and body weight gain. GP does not improve lipid profile in obese animals and however, ameliorates glucose tolerance in control and obese rats. GP did not improve the gastric emptying time or normalize the frequency of contractions disturbed by obesity. Surgery provides a remodeling process in the mucosa and muscularis mucosa layers, evidenced by leukocyte infiltration mainly in the mucosa layer. CONCLUSIONS & INFERENCES: Our study revealed the influence of the gastrointestinal tract on obesity is underestimated with pieces of evidence pointing out its important role as a target for surgical treatment.

Liraglutide modulates morpho-functional and inflammatory gastrointestinal responses in rats.

BACKGROUND: Obesity impairs homeostatic control of energy and is associated with chronic low-grade inflammation. Effects of glucagon-like peptide-1, the target in the gastrointestinal tract for anti-obesity drugs such as Liraglutide, were not properly associated with inflammation markers. This study investigated the effects of Liraglutide on metabolic and gastrointestinal parameters in a rat model of obesity. METHODS: Twenty-six Wistar rats with obesity were randomly distributed to receive saline (n = 10), 400 µg (n = 8), or 1200 µg of Liraglutide/kg/day (n = 8), subcutaneously for 30 consecutive days, once a day. Weight gain, feeding efficiency, caloric consumption, gastric motility, adiposity, histomorphometric, murinometric, biochemical parameters and cytokines TNF-α and TGF-ß1 in duodenal tissue were measured. Data were analysed by ANOVA, followed by Bonferroni post hoc or Kruskal-Wallis test, followed by Dunn's multiple comparison test. RESULTS: Liraglutide-treated animals had better feeding efficiency and higher caloric intake in a dose-dependent manner. Higher doses slowed gastric emptying and diminished the amplitude of gastric contractions. These effects were accompanied by decreases in intestinal muscle layer thickness and crypt depth. Liraglutide significantly reduced retroperitoneal and visceral white adipose tissue depots. High-dose treatment decreased levels of TNF-α and enhanced levels of TGF-ß1 in duodenal tissue. Liraglutide treatment provided significant reductions in total cholesterol, triglyceride and hepatic transaminases. CONCLUSIONS: Liraglutide reduced fat accumulation, improved metabolic parameters and downregulated levels of inflammatory signalling in duodenal tissue. Liraglutide at high doses controlled obesity-related outcomes, and such effects seemed to be driven by its action on glucagon-like peptide-1 receptors in the gastrointestinal tract slowing gastric motility.

Alternate-day fasting induces metabolic and morphofunctional changes in the gastrointestinal tract of male rats.

Alternate-day fasting (ADF) is a nutritional intervention with modulatory and overall protective effects, but its role in the gastrointestinal (GI) tract is still uncertain. The aim of this study was to investigate the influence of ADF on the metabolic patterns and morphofunctional motility of the GI tract in rats. Thirty-two male Wistar rats were allocated into groups: control for 15 days (CON 15, n = 8), control for 30 days (CON 30, n = 8), ADF for 15 days (ADF 15, n = 8), and ADF for 30 days (ADF 30, n = 8). Blood glucose, body weight, and food and water consumption were measured. Frequency and amplitude of gastric contractions as well as gastric emptying time, small intestinal transit time, and cecum arrival time were measured. Intestinal histomorphometric, relative weight of organs, lipidogram, and leptin levels were also evaluated. ADF decreased water consumption and food consumption. The weight gain decreased; however, the relative kidney weight increased. ADF triggered an increase in the amplitude of gastric contractions and accelerated gastric emptying. However, small intestinal transit time was delayed in both ADF groups. Total cholesterol, triglycerides, non-HDL cholesterol, and very low-density lipoprotein cholesterol levels decreased, whereas villus height, depth of the crypts and thickness of the circular, and longitudinal muscular layers of intestine increased after ADF. In conclusion, our results showed ADF exert an effect on both metabolism and GI motility and impacts on overall digestive functions.

Toxicological effects of the Morinda citrifolia L. fruit extract on maternal reproduction and fetal development in rats.

Morinda citrifolia L., also known as Noni, is widely used plant in folk medicine for various therapeutic purposes. However, reports on its effects during pregnancy are limited. Therefore, the objective of this study was to evaluate the effects of the M. citrifolia fruit extract on maternal performance and fetal development during pregnancy in rats. Pregnant Wistar rats (n = 12/group) were treated from gestational days (GD) 0-21 with water (control group) or the aqueous extract of M. citrifolia fruit at doses of 200, 400, or 750 mg/kg, orally. During pregnancy, clinical signs of toxicity, maternal weight, feed intake, and water consumption were noted. On GD 21, the rats were anesthetized and blood was collected to evaluate various biochemical parameters. During laparotomy, reproductive performance parameters were recorded, and fetuses were weighed and the anomalies analyzed. Reduced placental efficiency and fetal growth restriction were observed in the group treated with 400 mg/kg of M. citrifolia extract. The highest dose (750 mg/kg) augmented aspartate aminotransferase concentration and preimplantation losses, while reducing the number of live fetuses. Furthermore, both doses (400 and 750 mg/kg) of the plant extract caused fetal anomalies. In conclusion, consumption of high doses of the M. citrifolia aqueous extrac during pregnancy leads to maternal hepatotoxicity, anti-implantation effects, intrauterine growth restriction and fetal abnormalities, indicating that the plant fruit extract can be harmful to both the mother and the fetus.

BALB/c and C57BL/6 mouse strains influence gastric function outcomes with administration of cisplatin and dexamethasone

Abstract Our aim was to evaluate the effects of cisplatin and dexamethasone alone and combined on gastric contractility and histomorphometry of BALB/c and C57BL/6 mice. BALB/c and C57BL/6 male mice (8-week-old) were randomly separated into: Control; Cisplatin (7.5 mg/Kg); Dexamethasone (2.0 mg/Kg); and Dexamethasone plus Cisplatin (2.0 mg/Kg of dexamethasone 1-hour prior to 7.5 mg/Kg of cisplatin). Drugs were administered intraperitoneally for three days. Body weight and food intake were evaluated on 2nd day. Alternating Current Biosusceptometry technique was employed to measure gastric contractions on 3rd day. Afterward, mice were killed for gastric histomorphometric analysis. Cisplatin decreased food intake and caused bradygastria in BALB/c mice; however, the amplitude of gastric contractions decreased in both BALB/c and C57BL/6. Dexamethasone and cisplatin combined restored the gastric frequency and food intake only in BALB/c, but drug combination reduced the gastric amplitude of contractions in both strains. Dexamethasone alone increased gastric mucosa thickness in C57BL/6 and decreased muscular thickness in BALB/c. In conclusion, the mouse strains presented differences in acute effects of cisplatin and dexamethasone alone and combined on gastric function. This reinforces the importance of choosing the appropriate mouse strain for studying the acute effects of drugs on the gastrointestinal tract.

Gastrointestinal motility and morphology in mice: Strain-dependent differences.

BACKGROUND: BALB/c and C57BL/6 mice are widely used in biomedical research; however, the differences between strains are still underestimated. Our aims were to develop an experimental protocol to evaluate the duodenal contractility and gastrointestinal transit in mice using the Alternating Current Biosusceptometry (ACB) technique and to compare gastrointestinal motor function and morphology between BALB/c and C57BL/6 strains. METHODS: Male mice were used in experiments (a) duodenal contractility: animals which had a magnetic marker surgically fixed in the duodenum to determine the frequency and amplitude of contractions and (b) gastrointestinal transit: animals which ingested a magnetically marked chow to calculate the Oro-Anal Transit Time (OATT) and the Fecal Pellet Elimination Rate (FPER). The animals were killed after the experiments for organ collection and morphometric analysis. KEY RESULTS: BALB/c and C57BL/6 had two different duodenal frequencies (high and low) with similar amplitudes. After 10 hours of monitoring, BALB/c eliminated around 89% of the ingested marker and C57BL/6 eliminated 33%; OATT and FPER were slower for C57BL/6 compared with BALB/c. The OATT and amplitude of low frequency had a strong positive correlation in C57BL/6. For BALB/c, the gastric muscular layer was thicker compared to that measured for C57BL/6. CONCLUSIONS AND INFERENCES: The experimental protocol to evaluate duodenal contractility and fecal magnetic pellets output using the ACB technique in mice was successfully established. BALB/c strains had higher duodenal frequencies and a shorter time to eliminate the ingested marker. Our results showed differences in both motor function and gastrointestinal morphology between BALB/c and C57BL/6 strains.

NATURAL RUBBER - PROPOLIS MEMBRANE IMPROVES WOUND HEALING IN SECOND-DEGREE BURNING MODEL.

Our aim was to evaluate effects of natural rubber membrane (NR) associated with aqueous propolis extract (P) on the wound healing in rats burn model. The membranes were characterized for wettability and pore presence after the membrane preparation by casting the liquid solution in Petri dishes, at different temperatures (27 and 60 °C). Male Wistar rats were divided into treatment groups (n = 5 per group: control without treatment, silver sulfadiazine, NR, NRP) initiated immediately after second-degree burn and maintained during 10 days. The NRP membranes presented hydrophilic and porous characteristics. Macroscopic analysis from lesions showed that all groups presented crust formation. At the end of the experiment, the lesions treated with NRP membranes prepared at 60 °C had a higher regression percentage indicating a faster wound healing. The biopsies showed that the treatment with the NRP membranes induced a wound healing with collagen production, angiogenesis, reepithelization, and a small number of inflammatory cells, characterized by the crust detachment and the epithelium formation. In conclusion, NRP membranes are promising as a dressing for the burns treatment since were able to accelerate the healing process and tissue repair without the curative switch.

Electroacupuncture in rats infected with Strongyloides venezuelensis: effects on gastrointestinal transit and parasitological measurements.

OBJECTIVE: To investigate the effects of electroacupuncture (EA) at ST36 and CV12 on gastrointestinal transit and parasitological measurements during Strongyloides venezuelensis infection in rats. DESIGN: Rats were infected with S. venezuelensis and allocated to one of three groups that were infected and remained untreated (SV group, n=8), infected and treated with EA at CV12 (SV+CV12 group, n=8) or infected and treated with EA at ST36 (SV+ST36 group, n=8). EA was performed every 3 days over a 21-day period, at 4 mA intensity and 15 Hz frequency for 20 min. At 2 and 20 days post-infection (dpi), body weight, food and water intake, and faecal characteristics were monitored over a 24-hour period. Gastric emptying, caecal arrival time, small intestinal transit and eggs per gram (EPG) of faeces were calculated at 3, 9, 15 and 21 dpi. At 21 dpi, intestinal worm recovery was counted. RESULTS: EA at ST36 and CV12 slowed gastric emptying over the course of infection time. An accelerated intestinal transit was observed in the ST36 group, and after CV12 treatment the same effect was observed at 9 and 15 dpi. At 9 dpi, EPG was increased in the CV12 group. ST36 treatment decreased EPG at 9 and 15 dpi. At 21 dpi, both the ST36 and CV12 groups had increased EPG and worm numbers. No changes were observed in the other parameters analysed. CONCLUSIONS: EA at ST36 and CV12 provoked changes in gastrointestinal transit that may be beneficial to the host during S. venezuelensis infection; however, based on the number of worms and EPG at 21 dpi, the indication for EA in the treatment of strongyloidiasis needs to be carefully assessed.

Gastrointestinal Motility, Mucosal Mast Cell, and Intestinal Histology in Rats: Effect of Prednisone.

Our aim was to verify the effects of prednisone related to gastrointestinal motility, intestinal histology, and mucosal mast cells in rats. Two-month-old male Wistar rats were randomly assigned to control group (vehicle) animals receiving saline 0.9% (n = 7) or treated orally with 0.625 mg/kg/day of prednisone (n = 7) or 2.5 mg/kg/day of prednisone (n = 7) during 15 days. Mast cells and other histologic analyses were performed in order to correlate to gastric emptying, cecum arrival, and small intestine transit evaluated by Alternating Current Biosusceptometry. Results showed that prednisone in adult rats increased the frequency of gastric contractions, hastened gastric emptying, slowed small intestinal transit, and reduced mucosal mast cells. Histologically, the treatment with both doses of prednisone decreased villus height, whereas longitudinal and circular muscles and crypt depth were not affected. These findings indicate an impairment of intestinal absorption which may be linked to several GI dysfunctions and symptoms. The relationship between gastrointestinal motor disorders and cellular immunity needs to be clarified in experimental studies since prednisone is one of the most prescribed glucocorticoids worldwide.

Gastrointestinal disorders after immunosuppression: an experimental model to evaluate the influence of monotherapy on motility parameters.

NEW FINDINGS: What is the central question of this study? The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. What is main finding and its importance? In our experimental study, immunosuppressive drugs currently in use accelerated gastric emptying whilst increasing the frequency and amplitude of gastric contractions after treatment, except for Mycophenolate and azathioprine. Alternating current biosusceptometry is a useful tool to evaluate side-effects of drugs on the gastrointestinal tract, which will help in understanding the symptoms and improving clinical management of patients. The aim was to propose an animal model for investigating the effects of immunosuppressive monotherapy on gastrointestinal motility using a non-invasive biomagnetic technique. Male Wistar rats were randomly distributed into the following treatment groups: ciclosporin, tacrolimus, prednisone, sirolimus, mycophenolate mofetil, everolimus, azathioprine and control. Each animal was treated for 14 days by gavage with dosages ranging from 1 to 20 mg kg-1  day-1 considering the area-to-volume ratio and hepatic metabolism. Gastrointestinal transit and gastric contractility measurements were evaluated by alternating current biosusceptometry before and after treatment. Gastric emptying was faster in animals treated with tacrolimus, prednisone, sirolimus and everolimus compared with control animals (126.7 ± 12.7 min). There was a significant increase in the frequency of contractions after ciclosporin, tacrolimus, azathioprine and sirolimus treatment compared with control animals (4.6 ± 0.3 cycles min-1 ). Increases in the amplitude of contraction were observed after treatment with tacrolimus, sirolimus and everolimus compared with control rats (34.9 ± 6.0 dB). The results showed that our animal model was suitable for demonstrating that most immunosuppressive drugs currently in use impaired at least one gastrointestinal motility parameter. As a non-invasive technique, alternating current biosusceptometry is a potentially useful tool for evaluation of side-effects of drugs in gastrointestinal tract, helping us to understand the symptoms to improve clinical management of patients.

Role of sex hormones in gastrointestinal motility in pregnant and non-pregnant rats.

AIM: To correlate gastric contractility, gastrointestinal transit, and hormone levels in non-pregnant (estrous cycle) and pregnant rats using noninvasive techniques. METHODS: Female rats (n = 23) were randomly divided into (1) non-pregnant, (contractility, n = 6; transit, n = 6); and (2) pregnant (contractility, n = 5; transit, n = 6). In each estrous cycle phase or at 0, 7, 14, and 20 d after the confirmation of pregnancy, gastrointestinal transit was recorded by AC biosusceptometry (ACB), and gastric contractility was recorded by ACB and electromyography. After each recording, blood samples were obtained for progesterone and estradiol determination. RESULTS: In the estrous cycle, despite fluctuations of sex hormone levels, no significant changes in gastrointestinal motility were observed. Days 7 and 14 of pregnancy were characterized by significant changes in the frequency of contractions (3.90 ± 0.42 cpm and 3.60 ± 0.36 cpm vs 4.33 ± 0.25 cpm) and gastric emptying (168 ± 17 min and 165 ± 15 min vs 113 ± 15 min) compared with day 0. On these same days, progesterone levels significantly increased compared with control (54.23 ± 15.14 ng/mL and 129.96 ± 30.52 ng/mL vs 13.25 ± 6.31 ng/mL). On day 14, we observed the highest level of progesterone and the lowest level of estradiol compared with day 0 (44.3 ± 15.18 pg/mL vs 24.96 ± 5.96 pg/mL). CONCLUSION: Gastrointestinal motility was unaffected by the estrous cycle. In our data, high progesterone and low estradiol levels can be associated with decreased contraction frequency and slow gastric emptying.

Erythromycin versus neomycin in the treatment of hepatic encephalopathy in cirrhosis: a randomized double-blind study.

BACKGROUND: Hepatic encephalopathy (HE) is a severe complication in patients with hepatic cirrhosis, which causes numerous hospital admissions and deaths. Antibiotics are the best options in HE treatment, but head-to-head comparisons between these drugs are scarce. Erythromycin combines the antimicrobial effect and prokinetic properties in the same drug, but it has never been used in HE treatment. Our aim was to evaluate the efficacy of erythromycin as an HE treatment. METHODS: We achieved a randomized controlled trial of adult patients with HE and hepatic cirrhosis admitted in our hospital. After randomization, the subjects received either erythromycin 250 mg or neomycin 1 g orally QID until hospital discharge or prescription of another antibiotic. All subjects were blindly evaluated every day towards quantifying clinical, neuropsychometric, hepatic and renal exams. Statistical analysis was employed to compare the groups and correlate the variables with hospitalization duration. RESULTS: 30 patients were evaluated (15 treated with each drug). At hospital admission, the groups were homogeneous, but the erythromycin group subjects achieved a shorter hospitalization stay (p = 0.032) and a more expressive reduction in alanine aminotranspherase levels (p = 0.026). Hospitalization duration was positively correlated with C reactive protein levels measured previous to (p = 0.015) and after treatment (p = 0.01). CONCLUSIONS: In the sample evaluated erythromycin was associated with significant reductions in hospital stay and in alanine aminotranspherase values. Hospitalization time was positive correlated with C reactive protein levels measured before and after the treatments.