Proabsorptive action of gum arabic: regulation of nitric oxide metabolism in the basolateral potassium channel of the small intestine.

BACKGROUND: Gum arabic, a high-molecular-weight natural polysaccharide, has been shown to have proabsorptive properties in animal models of gastrointestinal disease that involve nitric oxide (NO). Gum arabic may indirectly regulate NO metabolism by creating an outward NO gradient, thus altering other intracellular NO-dependent mechanisms such as gating of the potassium (K+) channel. This hypothesis was further investigated using the K+ channel blocker, glybenclamide. METHODS: Following intraperitoneal injection of 4.5 mg/kg glybenclamide or saline, the jejunum of anesthetized rats was perfused with a standard oral rehydration solution in the presence or absence of 2.5 g/L gum arabic, as well as 1 mmol/L l-arginine to enhance NO production. Sodium, net water, and glucose absorption and unidirectional water movement were determined. RESULTS: Gum arabic showed regulatory capacity for NO-dependent metabolism by reducing net water absorption in the absence of arginine, and sodium absorption after arginine stimulation, in the absence of glybenclamide. Addition of gum arabic to oral rehydration solution, in glybenclamide pretreated animals, and in the absence of arginine, normalized sodium absorption, but was less effective in restoring net water transport. Injection of glybenclamide sharply decreased all absorption markers in arginine supplemented oral rehydration solution, which were at least partially restored by addition of gum arabic to the oral rehydration solution. In the presence of glybenclamide, the effects of arginine became antiabsorptive, as had those observed in preceding studies with high arginine concentration. Gum arabic partially or fully reversed alterations produced by perfused 1 mmol/L arginine. CONCLUSIONS: Some of the effects of gum arabic on the small intestine are likely caused by its ability to remove NO as it diffuses into the lumen, thus reducing NO concentration in the enterocyte and indirectly affecting the absorptive/secretory response of the gut, which leads to normalization of absorptive function. These findings are consistent with the previously shown gum arabic-scavenging properties of NO and support a potential therapeutic role for this product.

Effect of gum arabic in an oral rehydration solution on recovery from diarrhea in rats.

BACKGROUND: It has been shown that gum arabic, a soluble fiber, enhances water, electrolyte, and glucose absorption from oral rehydration solutions in jejunal perfusion of healthy rats and in animals with theophylline-induced secretion or chronic osmotic-secretory diarrhea. This report concerns a study of the effectiveness of an oral rehydration solution supplemented with gum arabic, during recovery from chronic osmotic secretory diarrhea in free-living rats. METHODS: Chronic diarrhea was induced in 60- to 80-g juvenile rats by providing a magnesium citrate-phenolphthalein solution as the sole fluid source for 7 days. This led to diarrhea characterized by dehydration, soft stools, increased cecal volume, decreased food and fluid intake and failure to gain weight. After 7 days of diarrhea, rats recovered for 24 hours with either tap water or an oral rehydration solution (90 mM Na, 111 mM glucose, 20 mM K, 80 mM chloride, 20 mM citrate) with or without 2.5 g/l gum arabic. RESULTS: Although all three solutions improved the diarrhea, optimal recovery from diarrhea was achieved with the gum arabic-supplemented oral rehydration solution. After 4 hours and 24 hours, rats drinking the gum arabic-supplemented solution gained more weight and had lower fecal output than rats receiving water or the rehydration solution without gum arabic. All three solutions normalized plasma osmolality after 24 hours. CONCLUSIONS: The positive effects of the gum arabic-supplemented rehydration solution on fluid and electrolyte absorption seen during jejunal perfusion also occurred during recovery from chronic osmotic secretory diarrhea, when free-living animals drank the solution ad libitum.

Modified starch enhances absorption and accelerates recovery in experimental diarrhea in rats.

Rice gruels have been used as home remedies to treat dehydration associated with diarrheal illness in developing countries. These preparations have produced conflicting results, most likely due to the heterogeneity of starch used. We investigated whether the modified tapioca starch, Textra (TX), at 5.0 or 10.0 g/L added to a 90 mmol/L Na+-111 mmol glucose oral rehydration solution (ORS) enhanced water and electrolyte absorption in two models of diarrhea. To induce a secretory state (model A), the jejunum of juvenile rats was perfused with 10 mmol/L theophylline (THEO) under anesthesia and then perfused with the solutions indicated above. To produce chronic osmotic-secretory diarrhea (model B), rats had a magnesium citrate-phenolphthalein solution as the sole fluid source for 1 wk, and then were perfused as the THEO-treated rats. Water, electrolyte, and glucose absorption were measured during both perfusions. As an extension of the perfusion studies, we compared how fast rats recovered from chronic osmotic diarrhea by offering them either water, ORS, or ORS containing 5.0 g/L TX along with solid food. Recovery rate markers were measured after 24 h and included weight gain, food and fluid intake, and stool output. In model A, addition of 5.0 g/L TX to ORS reversed Na+ secretion and improved net water as well as K+ and glucose absorption, compared with THEO-treated rats perfused with ORS without TX. In model B, addition of TX to ORS increased water, Na+, K+, and glucose absorption, compared with rats perfused without TX. Increasing TX from 5.0 to 10.0 g/L had no additional benefit. In recovery experiments, animals with free access to ORS with TX had significantly greater weight gain and decreased stool output compared with animals recovering with water or ORS without TX. Our experiments suggest that TX may be a useful additive to standard ORS to promote fluid and electrolyte absorption and may provide additional energy without increasing ORS osmotic load.

The role of dietary zinc in modifying the onset and severity of spontaneous diabetes in the BB Wistar rat.

The goal of this study was to determine whether zinc supplementation in the diet of diabetes-prone BB Wistar rats will delay or prevent the onset of overt diabetes. Male Wistar BB rats were fed diets containing either 1000 ppm (HZ), 50 ppm (NZ), or 1 ppm zinc (LZ) starting at 30 days of age. Non-diabetes-prone rats were fed NZ and designated as controls (NORM). Beginning at 60 days, the rats were checked for glycosuria and, if positive, were given an i.p. glucose tolerance test (IPGTT). All remaining animals underwent an IPGTT at 100 days and were sacrificed. At 90 days of age HZ rats had a lower incidence of diabetes (19%) than NZ (53%) or LZ (44%) animals (P < 0.015). By age 100 days, for the HZ group, there was a 60% reduction in the number of expected overt diabetic rats. HZ animals also had higher concentrations of both pancreatic and serum insulin and exhibited lower serum glucose and triglycerides. Immunohistochemistry of HZ rats was clearly different from NZ rats and showed evidence of nearly normal pancreatic endocrine activity. Data indicate that dietary treatment of diabetes-prone BB Wistar rats with zinc appears to be an effective approach for delaying or preventing the onset of diabetes in genetically predisposed rodents. This finding may suggest further experimental studies regarding dietary means for preservation of pancreatic function.

Copper absorption and bioavailability.

The human gastrointestinal system can absorb 30-40% of ingested copper from the typical diets consumed in industrialized countries. Experimental data support the existence of a carrier-mediated transport mechanism with an affinity constant in the micromolar range. Aging probably decreases the efficiency of copper homeostasis, resulting in higher plasma copper concentrations in the elderly. Physiologic differences may account for the higher cupremia of females. Supplements of minerals with similar chemical characteristics could reduce copper absorption. This property has pharmacologic applications in Wilson disease. Manipulation of the fiber content of the diet may have an indirect effect on copper bioavailability by altering the bioavailability of mineral antagonists. Proteins and soluble carbohydrates tend to improve copper absorption and bioavailability by enhancing its solubility and intestinal bulk flow. Organic acids, other than ascorbic acid, or agents that form low-molecular-weight chelates, are likely to have a positive effect on overall copper absorption. Conditions associated with malabsorption of macronutrients and gastrointestinal disease can impair copper uptake and contribute to suboptimal copper status.

Gum arabic promotes rat jejunal sodium and water absorption from oral rehydration solutions in two models of diarrhea.

BACKGROUND & AIMS: We have shown that addition of gum arabic (GA) to a 90 mmol/L sodium-111 mmol/L glucose oral rehydration solution (ORS) enhances its effectiveness for water and electrolyte absorption in normal rats. The present study extends these observations on GA in ORS to two rat models of diarrheal disease. METHODS: Juvenile rats were either treated for 1 week with magnesium citrate-phenolphthalein to produce chronic osmotic-secretory diarrhea or luminally exposed to 10 mmol/L theophylline to induce jejunal secretion. In both models jejunal perfusion was used to assess absorption. RESULTS: Addition of 2.5 or 5.0 g/L GA to ORS increased roughly twofold absorption of sodium, potassium, and water in the model of chronic osmotic-secretory diarrhea. Rats perfused with GA-supplemented ORS showed an expansion of the basolateral intercellular spaces between villus absorptive epithelial cells and the lamina propria, reflecting enhanced water and sodium absorption. Similarly, addition of 2.5, 5.0, or 10.0 g/L GA to the ORS neutralized theophylline-induced abolition of net sodium and potassium absorption and reversed water and glucose malabsorption. CONCLUSIONS: These experimental studies in models of diarrhea suggest that GA may be a useful additive to ORS for the potentiation of water and electrolyte absorption.

Oral rehydration solutions: enhanced sodium absorption with gum arabic.

OBJECTIVE: To assess whether the addition of gum arabic (GA) to oral rehydration solutions (ORS) of either 60 or 90 mM sodium enhances net water and sodium absorption in rats. METHODS: Perfusion of a jejunal segment of male juvenile rats under anesthesia, and determination of net water and sodium absorption, and unidirectional fluid movements using appropriate markers. RESULTS: Addition of 5 and 10 g/L of GA increased the rates of sodium removal from the intestinal lumen perfused with ORS containing either 60 or 90 mM sodium. Net water absorption was unaffected, although GA tended to facilitate bidirectional fluid movement. The alteration of solute transport rates by the addition of 10 g/L GA was associated with an expansion of the basolateral intercellular spaces. CONCLUSIONS: A soluble fiber such as GA appears to be an effective enhancer of sodium absorption from ORS when tested in experimental animals. Since GA does not affect viscosity, an alteration of solute diffusibility through the brush border membrane and changes in intercellular compartments may underlie the observed improvement of sodium absorption.

Oral hydration solutions in experimental osmotic diarrhea: enhancement by alanine and other amino acids and oligopeptides.

Improvement of sodium absorption during the administration of oral hydration solutions (OHS) could increase the efficacy of formulations used in the treatment of infantile diarrhea. To test this hypothesis, selected protein breakdown products were evaluated as absorption enhancers in OHS of different osmolalities and Na-to-glucose ratios in an animal model of osmotic diarrhea induced by cathartics. A very significant increase in water and Na absorption occurred in rats with diarrhea when they were perfused with a 90-mmol/L-Na, 111-mmol/L-glucose OHS containing 30 mmol/L of L-alanine (Ala). The same effect on Na retention was observed with a protein hydrolysate (PrH) in rats with diarrhea. Glycine was not effective. Other experimental OHS were ineffective in rats with diarrhea. The data indicate that in this animal model of chronic diarrhea Na transport enhancers, such as Ala and a PrH, are most efficacious in the presence of higher Na concentration.

Tyrosine supplementation in chronic experimental uremia.

The occurrence of low tyrosine tissue levels in uremic subjects, possibly due to impaired phenylalanine hydroxylation, suggests that tyrosine may be an essential amino acid in uremia. Additional dietary tyrosine may thus re-dress the deficiency. This study examined growth and tyrosine/phenylalanine metabolism in uremic rats during tyrosine supplementation. Rats made uremic (U) by 7/8 nephrectomy were compared to pair-fed (CP) and ad libitum-fed (CA), sham-operated controls. Two sets of each group of rats were studied after 21 days on the respective diets: I = Purina Lab Chow; II = same + 3.5% tyrosine. Plasma tyrosine was below normal in U and CP-fed diet I. With diet II, the tyrosine:phenylalanine ratio in U was lower than both CA and CP. In rats fed diet II, the tyrosine:phenylalanine ratio became indistinguishable among the three groups. Growth parameters in U and CP were similar, regardless of the diet. Body weight gain, tibial length, muscle mass, and tissue protein did not improve in uremic animals supplemented with tyrosine. The specific activity of liver phenylalanine hydroxylase in U was not different from CA or CP. However, loss of cortical renal mass appeared to be the major determinant of decreased kidney phenylalanine hydroxylation in experimental uremia. This alteration is likely to be the greatest contributory factor to the alteration of plasma levels of tyrosine and phenylalanine. The data presented do not support a proposed essentiality of tyrosine in uremia.