Effects Of Danshen On Pharmacokinetics Parameters And Biochemical Metabolism In Maternal And Fetal Sheep

Objectives: To further develop in vivo and in utero experimental fetal model in conscious and unstressed sheep, and using this fetal model to determine danshen concentrations and biochemical indexes in fetal blood for clinical use of Chinese medicine during pregnancy.Method: The timing pregnant sheep were anesthetized and operated for preparing ovine fetus in utero. After surgery, sheep were maintained and recovered for 4-5 days before testing. On testing day, three doses of denshen or 0.9% NaCl as the control was intravenously administrated into maternal vein via the catheter. Before and after the drug administration, both maternal and fetal blood samples were collected for analysis. HPLC approach was employed to determine blood danshen levels in bother maternal and fetal sheep. Danshen concentration in blood was measured by monitoring protocatechuic aldehyde levels. In addition, to test whether maternal administration of danshen may or not have effects on fetal liver functions, fat metabolism in blood, and the enzymes related to cellular metabolism, blood samples collected were tested and analyzed.Results: At 5, 30, 90 min following intravenous administration of danshen in maternal sheep, protocatechuic aldehyde was detected in fetal blood. This suggests that maternal danshen can enter the bloodstream in the fetal body in utero. Although danshen entered the fetal body, it did not show any effect on the blood values tested for liver functions and fat metabolism. In addition, no effects of danshen were observed for the enzymes related to the heart. However, after intravenous administration of danshen, fetal LDH and a-HBDH in blood were decreased (p < 0.05), while other blood values tested were not significantly changed.Conclusion: The present study demonstrates that danshen administrated in mothers could pass the blood-placenta-barrier, and enter into the fetal blood stream. There was dose-dependent effect for blood danshen concentrations in the fetus. Furthermore, danshen used during the last third of gestation had no negative effects on the indexes tested in the present study for fetal liver functions and fat metabolism in blood.