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).
Mattioli
Leone F
LF
Departments of Pediatrics, Surgery, and Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. lmattiol@kumc.edu
Holloway
Naomi B
NB
Thomas
James H
JH
Wood
John G
JG
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D005632:Fructose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008643:Mesentery / Q000098:blood supply*; D020030:Nitric Oxide Donors / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013096:Spermine / Q000031:analogs & derivatives / Q000378:metabolism; D014699:Venules / Q000187:drug effects / Q000378:metabolism*
D020030:Nitric Oxide Donors; C091861:spermine nitric oxide complex; D013096:Spermine; D005632:Fructose; D005947:Glucose