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Synergistic effects on pregnancy-termination activity of DL111-IT in combination with mifepristone
1Department of Pharmacology, School of Pharmacy, Zhejiang Medical University, Hangzhou, China.
Aim:
To clarify the role of DL111-IT when combined with mifepristone (Mif) on termination of early pregnancy.
Methods:
Progesterone receptors (PR) was measured using radioligand assay (RA), and peroxidase-antiperoxidase (PAP) immuno-histochemistry. Decidual cells (DC) were estimated using cell culture and histological examination (HE) (including fetus).
Results:
DL111-IT 100 mg.kg-1 i.m., Mif 5 mg.kg-1 i.g., DL111-IT 16 mg.kg-1 i.m. + Mif 1.5 mg.kg-1 i.g. and tea seed oil (TSO) 2 mL.kg-1 i.m. on d 7 of pregnancy in rats, DC and fetus of treated groups were found to be degenerated at 24 h after treatment, at 48 h after treatment, PAP labeling index (%) of uterus PR of 4 groups were 22 +/- 4, 18.7 +/- 2.9, 10.3 +/- 1.2, 52 +/- 15, respectively. Rats i.m. DL111-IT 100 mg.kg-1 24 h after treatment, the quantity of PR decreased by 47% vs that of TSO. The affinity of PR with Mif and progesterone did not change. Cultured human DC were exposed to DL111-IT and Mif 0-50 mg.L-1, alone or combinatively, for 24 h. LD50 (mg.L-1) were: DL111-IT 18.1 (15.1-21.4), Mif 25.0 (23.1-26.9), DL111-IT 5.0 plus Mif 3.5 (1.8-6.5) or Mif 5.0 plus DL111-IT 4.6 (1.1-7.3), respectively.
Conclusion:
DL111-IT enhanced action of Mif on DC, reduced quantity of PR, so the 2 drugs had the synergistic action in termination of early pregnancy.