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 production in mesenteric tissue (measured using the oxidant-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 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. J. Leukoc. Biol. 66: 59-66; 1999.

Ischemia-reperfusion injury in rats affects hydraulic conductivity in two phases that are temporally and mechanistically separate

“…There is also evidence that leukocyte-endothelial binding mediated by adhesion molecules and subsequent leukocyte emigration into tissues is proportional to the degree of endothelial-cell barrier dysfunction, further supporting a primary role for adhesion molecules as a central regulator of local and distant IR-related injury (25). Taken together, these findings add to the growing evidence suggesting that ROS production and WBC adhesion events are interconnected (15,31).…”

Nucleoside/nucleobase transport and metabolism by microvascular endothelial cells isolated from ENT1−/− mice

“…This hypoxanthine is metabolized intracellularly by xanthine oxidase with the consequent production of reactive oxygen species. Reactive oxygen species are believed to play a role in mediating the endothelial dysfunction observed in various pathological conditions including diabetes and ischemia-reperfusion injury (5,15,23). Therefore, understanding how MVECs handle hypoxanthine is important in the overall evaluation of purine metabolism in the vasculature.…”

Exenatide protects renal ischemia reperfusion injury in type 2 diabetes mellitus

“…[32] After a brief ischemia of the intestine, ROS are also increased and the increase is more pronounced in diabetes. [31] It is likely that inflammatory cells contribute to increased oxidative stress in T2DM kidneys after I/R. According to Sakr et al, pretreatment with a single injection of tacrolimus, 24 h prior to 60 min of ischemia was able to decrease the renal injury, and the effect was associated with decreased levels of TNF-α.…”

“…I/R. Elevated oxidative stress has been demonstrated in cerebral [30] and intestinal [31] I/R in DM rats. The combined oxidative stress from two sources may thus increase the total level of ROS.…”