Modulation of Small Intestinal Nitric Oxide Synthase by Gum Arabic

Abstract

Preceding studies have revealed that gum arabic (GA), a natural proteoglycan (≥250, 000 Da), has proabsorptive properties—as shown by increased sodium and water absorption—in normal rats, and especially in two animal models of diarrhea. Because nitric oxide (NO) metabolism is linked to gastrointestinal Physiology, the goals of this study were to determine whether GA modulated NO and to determine intestinal function in vivo when NO production was enhanced by l-arginine (Arg), added at either 1 or 20 mM. Mechanistically, the goal was also to determine whether GA was a NO scavenger and a small intestinal NO synthase (NOS) inhibitor. Using a glucose-electrolyte solution in rat jejunal perfusions we found that GA at ± 10 μM (2.5 g/l) decreased nitrite and nitrate formation, tending to normalize water, sodium, and glucose absorption when modified by Arg addition. In vitro tests, with oxyhemoglobin as a marker, showed that GA at ≥5 μM scavenged NO. For GA effects on NOS, small intestinal homogenate supematants (10, 000 g) from frozen tissues of either adult or 2-day-old rats were incubated for 1 hour at 37°C in the presence of 2 mM Arg and increasing GA concentrations (0-100 μM). GA produced a concentration-dependent inhibition of NOS, reaching approximately 31% inhibition with 5 μM GA and up to 51% with 50 μM GA. GA at 100 μM produced no further inhibition. The data indicate that GA, in addition to its ability to remove NO diffused into the intestinal lumen, may also partially inhibit intestinal NOS end thus modulate intestinal absorption through these mechanisms. Use of GA as a food additive may help in restoring or improving small Intestinal function in conditions where functional damage has occurred.