A New Murine Undernutrition Model Based on Complementary Feeding of Undernourished Children Causes Damage to the Morphofunctional Intestinal Epithelium Barrier.

BACKGROUND: Complementary feeding is critical in establishing undernutrition. However, experimental undernourished diets do not represent the amount of nutrients in the complementary diets of undernourished children. OBJECTIVES: To develop, validate, and evaluate the impact of a new murine model of undernutrition on the intestinal epithelium, based on the complementary diet of undernourished children from 7 countries with low-socioeconomic power belonging to the Malnutrition-Enteric Diseases (MAL-ED) cohort study. METHODS: We used the difference in the percentage of energy, macronutrients, fiber and zinc in the complementary diet of children without undernutrition compared with stunting (height-for-age Z-score < -2) for the MAL-ED diet formulation. Subsequently, C57BL/6 mice were fed a control diet (AIN-93M diet) or MAL-ED diet for 28 d. Weight was measured daily; body composition was measured every 7 d; lactulose:mannitol ratio (LM) and morphometry were evaluated on days 7 and 28; the cotransport test and analysis of intestinal transporters and tight junctions were performed on day 7. RESULTS: The MAL-ED diet presented -8.03% energy, -37.46% protein, -24.20% lipid, -10.83% zinc, +5.93% carbohydrate, and +45.17% fiber compared with the control diet. This diet rapidly reduced weight gain and compromised body growth and energy reserves during the chronic period (P < 0.05). In the intestinal epithelial barrier, this diet caused an increase in the LM (P < 0.001) and reduced (P < 0.001) the villous area associated with an increase in FAT/CD36 in the acute period and increased (P < 0.001) mannitol excretion in the chronic period. CONCLUSIONS: The MAL-ED diet induced undernutrition in mice, resulting in acute damage to the integrity of the intestinal epithelial barrier and a subsequent increase in the intestinal area during the chronic period. This study introduces the first murine model of undernutrition for the complementary feeding phase, based on data from undernourished children in 7 different countries.

Involvement of serotonergic pathways in gastric dysmotility induced by fat burning nutritional supplements in mice.

Fat burners are a category of nutritional supplements that are claimed to increase the metabolism and promote greater energy expenditure, leading to weight loss. However, little is known about the side effects on gastrointestinal motility. In this study, we evaluated the effect of ingestion with a fat burner named Thermbuterol® (THERM) on the gastric motility and food behavior of mice. THERM compounds were identified using nuclear magnetic resonance (NMR). Mice received variable doses of THERM (10, 50, 100 or 300 â€‹mg/kg, p.o.) or NaCl 0.15 â€‹M (control). Gastric emptying (GE) was assessed using the phenol red technique. Another set of mice was pretreated with intraperitoneal administration of hexamethonium (HEXA, 10 â€‹mg/kg), prazosin (PRAZ, 0.25 â€‹mg/kg), propranolol (PROP, 2 â€‹mg/kg), parachlorophenylalanine (PCPA, 300 â€‹mg/kg) or ondansetron (ONDA, 50 â€‹µg/kg) 30 â€‹min before THERM treatment for evaluation of GE. We assessed the gastrointestinal responsiveness in vitro as well as THERM's effects on food behavior. Caffeine was the major compound of THERM, identified by NMR. THERM 100 and 300 â€‹mg/kg decreased GE compared to the respective controls. Pretreatment with PRAZ or PROP did not prevent gastric dysmotility induced by THERM 100 â€‹mg/kg. However, the pretreatment with HEXA, ONDA or PCPA prevented GE delay induced by THERM. In vitro, THERM relaxed contractions in strips of longitudinal gastric fundus and duodenum. THERM also increased food intake, which was prevented by PCPA and ONDA treatments. THERM decreased GE of a liquid and increased food intake in mice, a phenomenon mediated by the autonomic nicotinic receptors and serotoninergic receptor.

Sildenafil inhibits duodenal contractility via activation of the NO-K+ channel pathway.

Phosphodiesterase type-5 (PDE5) specifically cleaves cyclic guanosine monophosphate (cGMP), a key intracellular secondary messenger. The PDE5 inhibitor sildenafil is a well-known vasodilator that also has gastrointestinal myorelaxant properties. In the present study, we further investigated sildenafil-induced myorelaxation in rat isolated duodenum, assessing its interaction with nitric oxide (NO) synthase and K(+) channel opening. The spontaneous contractions of duodenal strips were reversibly inhibited by sildenafil (0.1-300 microM) in a concentration-dependent manner [mean (95% confidence interval); EC(50) = 6.8 (2.7-17.3) microM]. The sildenafil-induced myorelaxation was significantly decreased by the NO synthase inhibitor N-nitro-L-arginine methyl ester [increasing the EC(50) value to 41.9 (26.1-67.3) microM]. Sodium nitroprusside or forskolin pretreatments enhanced the sildenafil-induced myorelaxation. In isolated strips pretreated with BaCl(2) (0.2 mM), 4-aminopyridine (4-AP, 3 mM), or glybenclamide (1 microM), the sildenafil-induced EC(50) value was significantly increased to 32.8 (19.1-56.4), 27.1 (15.2-48.3) and 20.1 (16.4-24.7) microM, respectively. Minoxidil (50 microM) or diazoxide (100 microM) also significantly attenuated the sildenafil-induced potency. In conclusion, the NO synthase/cyclic nucleotide pathway activation is involved in sildenafil-induced inhibition of spontaneous duodenal contractions. Its pharmacological action seems to be influenced by K(+) channel opening, especially the voltage-sensitive ones, being inhibited by 4-AP and K(ATP) channels, sensitive to glybenclamide.