The effect of tumor necrosis factor-alpha on D-fructose intestinal transport in rabbits.
Tumor necrosis factor-alpha (TNF-alpha) is an important immunoregulatory cytokine involved in septic responses during bacterial infection. The aim of this study was to examine the effect of TNF-alpha on the transport of D-fructose across rabbit jejunum. A sepsis condition was evoked by intravenous administration of this cytokine and hematological and plasma parameters were analyzed and body temperature was recorded. D-Fructose transport was assayed in rabbit jejunum. Sugar absorption in TNF-alpha treated rabbits was lower than in control animals. TNF-alpha decreased both the mucosal-to-serosal transepithelial flux and the transport across brush border membrane vesicles of D-fructose. The number of D-fructose transporters (GLUT5) was analyzed by Western blot in an attempt to explain this inhibition. TNF-alpha treated animals had lower levels of GLUT5, indicating a reduction in the expression of GLUT5 protein and therefore in transport capacity. The inhibition could also be related with the secretagogue effect of TNF-alpha on the gut since the intracellular tissue water was affected and the absence of chloride ion in the incubation medium partly removed the cytokine inhibition on sugar intestinal transport in treated rabbits. Finally, in terms of possible mediators involved in the TNF-alpha effect, nitric oxide and prostaglandins appeared to play a role in the inhibition of D-fructose intestinal uptake.
García-Herrera
J
J
Department of Pharmacology and Physiology, Veterinary Faculty, University of Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain.
Navarro
M A
MA
Marca
M C
MC
de la Osada
J
J
Rodríguez-Yoldi
M J
MJ
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005632:Fructose / Q000378:metabolism*; D051296:Glucose Transporter Type 5; D007213:Indomethacin / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D011817:Rabbits; D018805:Sepsis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D051296:Glucose Transporter Type 5; D009004:Monosaccharide Transport Proteins; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D005632:Fructose; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin