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Free radical defense mechanisms and neutrophil infiltration in postischemic skeletal muscle
J K Smith1, M B Grisham, D N Granger
1Department of Physiology and Biophysics, Louisiana State University Medical Center, School of Medicine, Shreveport 71130.
Abstract:
A growing body of experimental data indicates that reactive oxygen metabolites such as superoxide, hydrogen peroxide, and hydroxyl radicals may mediate the microvascular and parenchymal injury produced by reperfusion of ischemic skeletal muscle. One potential source of these reactive oxygen metabolites is the inflammatory neutrophil. To assess neutrophil accumulation in postischemic skeletal muscle, we measured tissue myeloperoxidase (MPO) activity in skeletal muscle biopsies taken during control, after 4 h of ischemia, and after 1 h of reperfusion. Tissue levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were measured in the same samples to identify alterations in tissue free radical defense mechanisms due to ischemia-reperfusion. Reperfusion of ischemic skeletal muscle was associated with a dramatic increase in tissue neutrophil content (as reflected by a 26-fold increase over control in tissue MPO activity after 1 h of reperfusion) and a concurrent 50% decrease in GSH content. Tissue CAT and SOD activities were unaffected by ischemia-reperfusion. These results suggest a possible relationship between ischemia-reperfusion-induced injury, neutrophil infiltration, and the reduction in tissue GSH.
Insights
Ischemia-reperfusion injury in skeletal muscle involves increased neutrophils and reduced glutathione (GSH). This study links neutrophil infiltration to GSH depletion, suggesting a role in tissue damage.
Area of Science:
- Biomedical Science
- Physiology
- Pathology
Background:
- Reactive oxygen metabolites may cause injury during skeletal muscle reperfusion after ischemia.
- Inflammatory neutrophils are a potential source of these damaging reactive oxygen metabolites.
Purpose of the Study:
- To investigate neutrophil accumulation in postischemic skeletal muscle.
- To assess alterations in antioxidant defense mechanisms following ischemia-reperfusion injury.
Main Methods:
- Myeloperoxidase (MPO) activity was measured in skeletal muscle biopsies to quantify neutrophil content.
- Levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were assessed to evaluate antioxidant status.
Main Results:
- Reperfusion significantly increased neutrophil infiltration, indicated by a 26-fold rise in MPO activity.
- Tissue GSH levels decreased by 50% after reperfusion.
- Superoxide dismutase (SOD) and catalase (CAT) activities remained unchanged.
Conclusions:
- Ischemia-reperfusion injury in skeletal muscle is associated with substantial neutrophil infiltration.
- The observed reduction in tissue GSH suggests a link between neutrophil activity and depletion of this key antioxidant.
- These findings highlight a potential mechanism involving neutrophils and GSH in the pathogenesis of ischemia-reperfusion injury.