Effects of intragastric fructose and dextrose on mesenteric microvascular inflammation and postprandial hyperemia in the rat.

OBJECTIVES: Fructose superfused on the mesenteric venules of rats induces microvascular inflammation via oxidative stress. It is unknown whether intragastric fructose exerts a similar effect and whether fructose impairs postprandial hyperemia (PPH). The goals were to determine whether intragastric fructose administration promotes leukocyte adherence and whether fructose, owing to its oxidative properties, may also impair nitric oxide-dependent PPH in the mesenteric microcirculation of rats. METHODS: Leukocyte adherence to mesenteric venules, arteriolar velocity, and diameter were measured in Sprague-Dawley rats before and 30 minutes after intragastric (1 mL 0.5 M, ~0.3 g/kg) dextrose (n = 5), fructose (n = 6), and fructose after intravenous injection of the antioxidant α-lipoic acid (ALA, n = 6). RESULTS: Only fructose increased leukocyte adherence: control 2.3 ± 0.3 per 100 µm; fructose 9.7 ± 1.4 per 100 µm (P < .001). This effect was independent of changes in venular shear rate: control 269 ± 48 s(-1); fructose 181 ± 27 s(-1) (P > .05, r(2) = 0.083 for shear rate vs leukocyte adherence). Dextrose had no effect on leukocyte adherence: control 1.52 ± 0.13 per 100 µm; dextrose 2.0 ± 0.7 per 100 µm (P > .05). ALA prevented fructose-induced leukocyte adherence: control 1.9 ± 0.2 per 100 µm; fructose + ALA 1.8 ± 0.3 per 100 µm (P > .05). Neither fructose nor dextrose induced PPH: arteriolar velocity: control 3.3 ± 0.49 cm/s, fructose 3.06 ± 0.34 cm/s (P > .05); control 3.3 ± 1.0 cm/s, dextrose 3.15 ± 1.1 cm/s (P > .05); arteriolar diameter: control 19.9 ± 1.10 µm, fructose 19.7 ± 1.0 µm (P > .05); control 21.5 ± 2.6, dextrose 20.0 ± 2.7 µm (P > .05). CONCLUSIONS: Intragastric fructose induced leukocyte adherence via oxidative stress. Neither dextrose nor fructose induced PPH, likely because of the inhibitory effect of anesthesia on splanchnic vasomotor tone.

Fructose, but not dextrose, induces leukocyte adherence to the mesenteric venule of the rat by oxidative stress.

Recent evidence indicates that fructose is a pro-inflammatory molecule. Oral fructose induces serum and kidney inflammatory intercellular adhesion molecule-1 (ICAM-1) in rats. Fructose also induces ICAM-1 expression in human aortic endothelial cells (HAEC) and monocyte chemoattractant protein-1 in proximal tubular renal cells. It is not known whether fructose may directly promote inflammation on the intestinal microcirculation. Accordingly, using intravital microscopy we studied the effect of topical fructose and dextrose on leukocyte adherence to the mesenteric venule of the rat. Leukocyte adherence was determined during a control period and after fructose was added to the mesentery, in the presence or absence of the NO donor spermine NONO-ate (SNO), and after i.v. injection of the antioxidant lipoic acid (LA). In separate experiments, we examined the effect of topical dextrose on leukocyte adherence to the mesenteric venule. Venular shear rate was calculated. Fructose, but not dextrose, induced significant inflammation independent of shear rate. This effect was completely blocked by SNO and LA, suggesting that fructose induces inflammation via reactive oxygen species (ROS) generation. These results suggest that fructose present in formulas may adversely affect the intestinal microcirculation of premature infants and potentially contribute to the pathogenesis of necrotizing enterocolitis (NEC).