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Oxidized and Free Whole Blood Thiols in Preeclampsia

From the Departments of Gastroenterology and Obstetrics and Gynecology, University Hospital St. Radboud, Nijmegen, Netherlands.

Address reprint requests to: Wilbert H. M. Peters, PhD Department of Gastroenterology University Hospital St. Radboud P.O. Box 9101 6500 HB Nijmegen Netherlands E-mail: w.peters{at}gastro.azn.nl

Objective: To measure levels of oxidized and free thiols in whole blood of normotensive pregnant and preeclamptic women and evaluate the role of oxidative stress.

Methods: We measured whole blood oxidized and free levels of cysteine, homocysteine, cysteinylglycine, and glutathione by high performance liquid chromatography in women with normotensive pregnancies (n = 50), preeclampsia (n = 29), and preeclampsia complicated by the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 16).

Results: Oxidized and free levels (median [range], µmol/L) of cysteine and homocysteine were higher in women with preeclampsia than normotensive pregnancies (45 [27–81] versus 29 [9–91], P < .001, and 98 [57–193] versus 69 [33–215], P < .001; 0.8 [0.2–4.4] versus 0.4 [0.01–1.6], P < .001, and 2.1 [0.7–9.4] versus 1.2 [0.2–21.2], P < .01; respectively). The ratios of free to oxidized cysteine, homocysteine, and cysteinylglycine were lower in preeclampsia than normotensive pregnancy (2.2 [1.3–3.0] versus 2.4 [1.7–4.3], P < .001; 2.3 [0.5–5.4] versus 2.9 [1.1–24], P < .001; 4.1 [2.3–11.6] versus 5.4 [2.6–24.3], P < .02, respectively), indicating a shift in favor of the oxidized form of those thiols. In HELLP syndrome, levels of oxidized and free cysteine and levels of oxidized homocysteine were higher than normal (44 [33–63] versus 29 [9–91], P < .001, and 102 [82–133] versus 69 [33–215], P < .001; 1.0 [0.3–2.9] versus 0.4 [0.01–1.6], P < .001, respectively). No significant differences were found in oxidized glutathione levels in women with preeclampsia (22 [5–49] versus 17 [2–60], P = .06) or free levels in preeclamptic women with HELLP syndrome (757 [624–993] versus 842 [539–1516], P = .09) as compared with normotensive pregnant women. The ratios of free to oxidized cysteinylglycine and glutathione were higher in women with HELLP syndrome than in those with preeclampsia (5.4 [3.3–12.7] versus 4.1 [2.3–11.6], P = .02, and 56 [28–124] versus 45 [16–166], P = .02, respectively).

Conclusion: Significantly lower ratios of free to oxidized cysteine, homocysteine, and cysteinylglycine in preeclampsia might indicate oxidative stress.

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