Xanthine oxioreductase is the
holoenzyme responsible for terminal
purine catabolism. Under conditions of metabolic stress or heightened proinflammatory
cytokine production, this
enzyme is preferentially in its oxidized form,
xanthine oxidase, with catalytic action that generates
uric acid and the
free radical superoxide. As
preeclampsia is characterized by heightened
inflammation, oxidative stress, and
hyperuricemia, it has been proposed that
xanthine oxidase plays a pivotal role in this hypertensive disorder of pregnancy. We sought to determine whether
xanthine oxidase protein content was higher in maternal tissue of preeclamptic mothers, compared to healthy pregnant controls, using immunohistochemical analysis of skin biopsies. We further compared
xanthine oxidase immunoreactivity in skin biopsies from preeclamptic women and patients with several inflammatory conditions. In preeclamptic women, intense
xanthine oxidase immunoreactivity was present within the epidermis. By contrast, only very faint
xanthine oxidase staining was observed in skin biopsies from healthy pregnant controls. Further, a role for
inflammation in the increase of
xanthine oxidase was suggested by similar findings of heightened
xanthine oxidase immunoreactivity in the skin biopsies from nonpregnant individuals diagnosed with conditions of systemic
inflammation. The finding of increased
xanthine oxidase in maternal tissue, most likely as the result of heightened maternal
inflammation, suggests maternal
xanthine oxidase as a source of
free radical and
uric acid generation in
preeclampsia.