Allopurinol has been shown to provide significant protection against
ischemia/reperfusion-induced microvascular and parenchymal cell injury. It has been hypothesized that the protection seen with
allopurinol after
ischemia/reperfusion (I/R) is caused by inhibition of
xanthine oxidase. However, recent reports suggest that the beneficial effects of
allopurinol in I/R may be caused by direct
free radical scavenging. The objective of this study was to determine whether the regimen of
allopurinol administration used in most I/R studies leads to a significant modification of the
free radical scavenging properties of extracellular fluid (ECF), i.e., plasma and lymph. Plasma and intestinal lymph samples obtained from both control and
allopurinol-treated cats were used to assess the following: 1)
allopurinol and
oxypurinol concentrations, 2)
xanthine oxidase inhibition, 3)
myoglobin-catalyzed
linolenic acid peroxidation, 4)
hypochlorous acid scavenging, and 5)
protein and nonprotein sulfhydryl content. ECF from
allopurinol-treated animals contained approximately 10 microM each of
allopurinol and
oxypurinol. Ten percent ECF resulted in 80% inhibition of
xanthine oxidase activity. Comparable volumes of control ECF did not inhibit
xanthine oxidase. Furthermore,
allopurinol treatment did not enhance the
antioxidant properties of ECF. The results of this study do not support the contention that the beneficial effects of
allopurinol in I/R injury are caused by the scavenging of
oxidants produced in ECF by activated granulocytes.