HYPERURICEMIA AND XANTHINE-OXIDASE IN PREECLAMPSIA, REVISITED

Hyperuricemia is associated with the severity of preeclampsia and with fetal outcome. Traditionally the high uric acid concentration in pree clampsia has been attributed solely to renal dysfunction. Preeclampsia is also characterized by increased free radical formation and elevate d oxidative stress. Xanthine dehydrogenase/oxidase produces uric acid. Xanthine dehydrogenase/oxidase is present as two isoforms in vivo. Ur ic acid production is coupled with formation of reactive oxygen specie s when the enzyme is in the oxidase form. Several factors can increase the holoenzyme activity and the conversion of xanthine dehydrogenase/ oxidase to its oxidase form. These factors include hypoxia-reperfusion , cytokines, and increased substrate availability (xanthine and hypoxa nthine). Preeclampsia is characterized by hyperuricemia and signs of i ncreased formation of reactive oxygen species and decreased levels of antioxidants. Preeclampsia is also characterized by shallow implantati on, producing a relatively hypoxic maternal-fetal interlace, and incre ased turnover of trophoblast tissue, which can result in higher xanthi ne and hypoxanthine concentrations and higher levels of circulating cy tokines. These mechanisms can lead to increased production of uric aci d and free radicals and contribute to the hyperuricemia and increased oxidative stress present in preeclampsia.