Increased oxidant generation in the metabolism of hypoxanthine to uric acid and endothelial dysfunction in early-onset and late-onset preeclamptic women

• Published in: The journal of maternal-fetal & neonatal medicine 2012-12, Vol.25 (12), p.2662-2666
• Main Authors: Watanabe, Kazushi, Mori, Toshitaka, Iwasaki, Ai, Kimura, Chiharu, Matsushita, Hiroshi, Shinohara, Koichi, Wakatsuki, Akihiko
• Format: Article
• Language: English
• Subjects: Adult; Age of Onset; Case-Control Studies; Early-onset preeclampsia; endothelial dysfunction; Endothelium, Vascular - physiopathology; Female; Gestational Age; Humans; Hypoxanthine - blood; Hypoxanthine - metabolism; late-onset preeclampsia; Oxidants - blood; Oxidants - metabolism; oxidative stress; Pre-Eclampsia - blood; Pre-Eclampsia - epidemiology; Pre-Eclampsia - metabolism; Pre-Eclampsia - physiopathology; Pregnancy; Reactive Oxygen Species - blood; Reactive Oxygen Species - metabolism; Severity of Illness Index; Up-Regulation; uric acid; Uric Acid - blood; Uric Acid - metabolism; Young Adult
• ISSN: 1476-7058; 1476-4954
• DOI: 10.3109/14767058.2012.705396

Objective: The purpose of this study was to evaluate the association of vascular endothelial dysfunction with increased oxidant generation in the metabolism of hypoxanthine to uric acid in early-onset compared to late-onset preeclampsia. Methods: We investigated 12 women with early-onset preeclampsia, 14 women with late-onset preeclampsia, and 20 women with uncomplicated pregnancies. We measured serum derivatives of reactive oxygen metabolites (d-ROMs) as a marker of oxygen free radicals, serum biological antioxidant potential (BAP), hypoxanthine, uric acid, uric acid clearance (CUA), and flow-mediated vasodilation (FMD) as a marker of endothelial function in preeclamptic women. Results: Concentration of d-ROMs was significantly higher in both preeclamptic groups compared to the control group. Plasma levels of uric acid were significantly elevated in both preeclamptic groups compared to the control group. Plasma levels of hypoxanthine were significantly higher in early-onset preeclamptic women compared to controls, but not in late-onset preeclamptic women. CUA was significantly lower in late-onset preeclamptic women compared to controls, but not in early-onset preeclamptic women. The concentrations of hypoxanthine and uric acid correlated positively with the concentration of d-ROMs in all pregnant women. FMD was significantly lower in both preeclamptic groups compared with controls, but FMD in the early-onset preeclamptic group was significantly lower than in the late-onset preeclamptic group. Conclusions: We found that increased oxidant generation during metabolism of hypoxanthine to uric acid may impair endothelial function in early-onset preeclampsia.