Existence of Compensatory Defense Mechanisms Against Oxidative Stress and Hypertension in Preeclampsia

Abstract

Objective: Preeclampsia is a complex obstetrical syndrome characterized by hypertension and proteinuria. This syndrome is associated with oxidative stress, antioxidant imbalance and impaired production of vasoactive eicosanoids such as thromboxane A₂ (TXA₂), a potent vasoconstrictor, and prostacyclin (PGI₂), a well-known vasodilator. We hypothesized that there was a relationship between antioxidant vitamins, such as vitamin E and coenzyme Q₁₀ (CoQ₁₀), and the production of vasoactive eicosanoids— PGI₂ and TXA₂—potentially regulated by pro-oxidants and antioxidants in preeclampsia. Methods: Therefore, the plasma levels of vitamin E, CoQ₁₀, TXA₂ and PGI₂ in normotensive (n = 30) and preeclamptic (n = 29) pregnancies were evaluated. Reduced and oxidized forms of vitamin E and CoQ₁₀ in blood were measured using a HPLC coupled to electrochemical detection. The levels of TXB₂ and 6-keto-PGF_1α, stable metabolites of TXA₂ and PGI₂ respectively, were measured by ELISA. Results: The CoQ₁₀ oxidized/reduced ratio was significantly higher in preeclamptic compared to normotensive pregnancies (p = 0.04). A strong correlation between plasma levels of reduced vitamin E and CoQ₁₀, corrected for apolipoprotein B, was observed only in preeclampsia (r = 0.69, p < 0.0001). The 6-keto-PGF_1α/TXB₂ ratio was higher in preeclampsia than in controls (p = 0.02), and this ratio was correlated to the oxidized/reduced ratio of both, vitamin E and CoQ₁₀ in all pregnancies (p <0.023). Conclusion: The data indicated that CoQ₁₀ is a sensitive marker of oxidative stress in preeclampsia. The correlation between vitamin E and CoQ₁₀ suggested a coordinated defense mechanism against oxidation. Furthermore, the higher 6-keto-PGF_1α/TXB₂ ratio that strongly correlated with oxidative stress markers, suggests a mechanism developed by the maternal cardiovascular system to counteract hypertension during preeclampsia.

Keywords:

• Vitamin E
• Coenzyme Q₁₀
• Thromboxane
• Prostacyclin
• Preeclampsia
• Blood