Fructose-1,6-biphosphate and nucleoside pool modifications prevent neutrophil accumulation in the reperfused intestine.
Fructose-1,6-biphosphate (F16BP) attenuates ischemia/reperfusion (I/R) injury by inhibiting microvascular leukocyte adhesion or reducing neutrophil-derived oxygen free-radical production, but the causes of this action, the mechanisms in vivo, and the possible implication of nucleoside pool modifications are still controversial issues. We explored whether F16BP's inhibition of free-radical production and neutrophil recruitment is a result of its effect on adenosine (Ado) accumulation during intestinal I/R injury. The effects of F16BP administration were tested on the nucleotide/nucleoside metabolism at the end of the ischemic period and on microvascular neutrophil recruitment and free-radical production after reperfusion in vivo, in the presence or absence of Ado deaminase (ADA). Infusion of F16BP markedly increased endogenous Ado, decreased xanthine accumulation during the ischemic period, and inhibited neutrophil recruitment and subsequent neutrophil free-radical generation during reperfusion. Administration of ADA reversed these processes. The results provide strong evidence that F16BP prevents neutrophil accumulation and neutrophil free-radical generation during intestinal I/R by a key mechanism that modifies the nucleoside pool, leading to an endogenous accumulation of Ado and to a reduction of xanthine during ischemia.
Sola
Anna
A
Department of Medical Bioanalysis, Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC-IDIBAPS), C/Rosselló 161, 7a Planta, 08036 Barcelona, Spain.
Panés
Julián
J
Xaus
Carme
C
Hotter
Georgina
G
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D005609:Free Radicals / Q000378:metabolism; D005635:Fructosediphosphates / Q000008:administration & dosage / Q000494:pharmacology*; D007422:Intestines / Q000473:pathology; D007511:Ischemia / Q000378:metabolism; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009705:Nucleosides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D019820:Xanthine / Q000378:metabolism
D005609:Free Radicals; D005635:Fructosediphosphates; D009705:Nucleosides; D019820:Xanthine; D000241:Adenosine; C029063:fructose-1,6-diphosphate