Reperfusion-induced oxidative stress in diabetes: cellular and enzymatic sources.
Reactive oxygen metabolites (ROMs) have been implicated in the pathogenesis of the inflammatory response to ischemia/reperfusion (I/R), which is exacerbated in diabetes. This study revealed an increased (P < 0.01) ROMs production in mesenteric tissue (measured using the oxidant-sensitive fluorochrome dihydrorhodamine 123) after I/R in control and diabetic rats, with larger increments (P <0.0001) observed in the latter group, that was associated with an increased inflammatory response measured by intravital microscopy. Either xanthine oxidase inhibition, superoxide scavenging, ICAM-1 immunoneutralization, or blockade of platelet-activating factor or leukotrienes effectively reduced leukocyte recruitment and ROMs production in control and diabetic rats. Moreover, neutrophils from diabetic rats showed an enhanced production of ROMs in vitro in basal and stimulated conditions. We conclude that the oxidative stress during reperfusion is markedly enhanced in diabetes and this appears to result from increased leukocyte recruitment and a higher capacity of diabetic leukocytes to generate ROMs in response to stimulation.
Gastroenterology Department, Institut Clínic de Malalties Digestives, IDIBAPS, Hospital Clínic, Barcelona, Spain.
A
A
Salas
J
J
Panés
J I
JI
Elizalde
D N
DN
Granger
J M
JM
Piqué
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors; D008297:Male; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D018384:Oxidative Stress; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013311:Streptozocin; D013482:Superoxide Dismutase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D005609:Free Radicals; D010972:Platelet Activating Factor; D018799:Intercellular Adhesion Molecule-1; D007975:Leukotriene B4; D013311:Streptozocin; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase