Comparison of ex vivo inhibitory effect between 2‐hydroxyestradiol and its 17‐sulfate on rat hepatic microsomal lipid peroxidation

Two endogenous antioxidants that are speculated to be defense substances against preeclampsia, 2‐hydroxyestradiol (2‐OH‐E2) and its 17‐sulfate, 2‐hydroxyestradiol 17‐sulfate (2‐OH‐E2‐17‐S), were administered to rats to compare their inhibitory effects on hepatic microsomal lipid peroxidation, and the lipid peroxides were determined in NADPH‐ and ascorbic acid‐dependent systems. The two catechols showed a strong inhibitory effect on lipid peroxidation in both systems, and the effect was dose dependent. However, a large difference was observed in their inhibition patterns. After administration of 2‐OH‐E2, the effect appeared immediately and decreased gradually with time. In contrast, the effect of 2‐OH‐E2‐17‐S appeared some time after administration and persisted for a longer time. Both catechols also showed a striking difference in their dynamics. After administration, 2‐OH‐E2 was detected in the blood together with its metabolites, 2‐methoxyestradiol and 2‐methoxyestrone, and they disappeared immediately. In contrast, 2‐OH‐E2‐17‐S was present in the blood for a longer time together with its O‐methylated product, 2‐methoxyestradiol 17‐sulfate, but disappeared from liver microsomes within 2 h after administration. The results imply no occurrence of a direct inhibition effect of 2‐OH‐E2‐17‐S.