Pathology · Cell Injury, Death and Adaptations (Apoptosis, Necrosis, Free Radicals)

In ischemia-reperfusion injury, the burst of reactive oxygen species during reperfusion causes greater damage than ischemia alone. The most important source of this ROS burst in cardiomyocytes at the moment of reperfusion is:

  • A Xanthine oxidase acting on accumulated hypoxanthine
  • B NADPH oxidase activation in mitochondria
  • C Cyclooxygenase-2 induction by reperfusion
  • D Cytochrome P450 in the smooth endoplasmic reticulum
Correct answer: A. Xanthine oxidase acting on accumulated hypoxanthine

Explanation

During ischemia, ATP is degraded to hypoxanthine and xanthine dehydrogenase is converted to xanthine oxidase by calcium-activated proteases. Upon reperfusion with oxygen, xanthine oxidase catalyzes conversion of accumulated hypoxanthine to xanthine and uric acid, generating superoxide radicals. NADPH oxidase is important in neutrophils; COX-2 produces prostaglandins, not ROS as the primary reperfusion burst; CYP450 is involved in drug metabolism.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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