In ischemia-reperfusion injury, the burst of reactive oxygen species upon reperfusion is primarily generated by which mechanism?
- A Xanthine oxidase converting hypoxanthine to xanthine using molecular oxygen as electron acceptor ✓
- B Mitochondrial complex I and complex III reverse electron transport generating superoxide
- C NADPH oxidase (NOX2) activation in endothelial cells triggered by Ca2+ influx
- D Uncoupled eNOS generating superoxide instead of nitric oxide due to BH4 depletion
Explanation
During ischemia, ATP is catabolized to AMP, then adenosine, hypoxanthine, and xanthine — accumulating as ischemia continues. Simultaneously, xanthine dehydrogenase is converted to xanthine oxidase by calcium-activated proteases. Upon reperfusion, molecular oxygen becomes available and xanthine oxidase converts accumulated hypoxanthine and xanthine to uric acid while reducing O2 to superoxide (O2•−) and H2O2, producing a burst of ROS that causes lipid peroxidation, protein oxidation, and DNA damage. This is the classic and most established mechanism. Mitochondrial RET (complex I reverse electron transport) is increasingly recognized but predominantly in hypoxic conditions (anoxia), not primarily the reperfusion burst mechanism taught in standard pathology.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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