Reperfusion-induced oxidative stress in diabetes: cellular and enzymatic sources

Abstract: 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 F 0.01) ROMs produc-tion in mesenteric tissue (measured using the oxi-dant-sensitive fluorochrome dihydrorhodamine 123) after I/R in control and diabetic rats, with larger increments (P F0.0001) observed in the latter group, that was associated with an increased inflammatory response measured by intravital mi-croscopy. Either xanthine oxidase inhibition, super-oxide scavenging, ICAM-1 immunoneutralization, or blockade of platelet-activating factor or leukotri-enes 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. J. Leukoc. Biol. 66