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Reperfusion-induced oxidative stress in diabetes: cellular and enzymatic sources
A Salas1, J Panés, J I Elizalde
1Gastroenterology Department, Institut Clínic de Malalties Digestives, IDIBAPS, Hospital Clínic, Barcelona, Spain.
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 < 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.
Insights
Diabetes exacerbates ischemia/reperfusion injury by increasing reactive oxygen metabolites (ROMs) and leukocyte recruitment. Diabetic leukocytes show heightened ROMs production, contributing to enhanced oxidative stress during reperfusion.
Area of Science:
- Biomedical Science
- Physiology
- Pathology
Background:
- Reactive oxygen metabolites (ROMs) play a role in ischemia/reperfusion (I/R) injury.
- Diabetes mellitus exacerbates the inflammatory response to I/R.
Purpose of the Study:
- To investigate the role of ROMs and leukocyte recruitment in I/R injury in diabetic rats.
- To compare ROMs production and inflammatory responses between control and diabetic rats following I/R.
Main Methods:
- Measurement of ROMs production using dihydrorhodamine 123 in mesenteric tissue.
- Assessment of leukocyte recruitment via intravital microscopy.
- Evaluation of interventions including xanthine oxidase inhibition, superoxide scavenging, and blockade of inflammatory mediators.
Main Results:
- Increased ROMs production and leukocyte recruitment were observed in both control and diabetic rats after I/R, with significantly higher levels in diabetic rats.
- Interventions targeting ROMs production and inflammatory pathways reduced leukocyte recruitment and ROMs.
- Neutrophils from diabetic rats exhibited enhanced in vitro ROMs production.
Conclusions:
- Oxidative stress during reperfusion is significantly amplified in diabetes.
- Increased leukocyte recruitment and heightened ROMs generation capacity by diabetic leukocytes contribute to exacerbated I/R injury in diabetes.