The effects of ulipristal on Bax/Bcl-2, cytochrome c, Ki-67 and cyclooxygenase-2 expression in a rat model with surgically induced endometriosis.

Abstract

OBJECTIVE:

To evaluate the effect of ulipristal on Bax/Bcl-2, cytochrome C, Ki-67 and cyclooxygenase-2 expression in surgically induced endometriosis in a rat model.

STUDY DESIGN:

We conducted a prospective, randomized, controlled, experimental study at the Experimental Research Center of the Iuliu Hatieganu University of Medicine and Pharmacy in Cluj-Napoca, Romania. Endometriosis was induced in 40 female Wistar albino rats by transplanting two autologous fragments of uterine horn onto bowel mesentery. After a 4-week induction period, we formed two groups: the first group was treated with ulipristal (UPA+) for 8 weeks, while the second group was treated only with the vehicle used for ulipristal (UPA-). We measured the volumes and masses of the implants both before and after treatment. A pathologist examined the sections microscopically for histological hallmarks of endometriosis. Immunostaining for Bax/Bcl-2, cytochrome C, Ki-67 and cyclooxygenase-2 (COX-2) was assessed in both groups.

RESULTS:

Ulipristal reduced the average implant volume and mass, indicating that the drug is effective (P=0.01). The treatment induced a greater than 50% reduction in the volume and mass of endometrial implants, and the histological findings correspond to this result. The overall Bax positivity rate was higher in the group treated with ulipristal (42.37% vs. 21.05% for UPA+ and UPA-, respectively) (P=0.0062). The overall Bcl-2 positivity rate was smaller in the group treated with ulipristal (15% vs. 40% for UPA+ and UPA-, respectively) (P=0.0593). The cytochrome C global positivity rate was 5% in the UPA- group and increased to 50% in the UPA+ treatment group (P<0.0001). The COX-2 positivity rate decreased from 75% in the UPA- treatment group to 10% in the UPA+ treatment group (P<0.0001) and the Ki67 positivity rate also decreased from 55% in the UPA- group to 10% in the UPA+ treatment group (P<0.0002).

CONCLUSIONS:

Treatment with ulipristal contributed to the regression and atrophy of endometriotic lesions in rats. The immunohistochemical expression profiles of Bax/Bcl-2 and cytochrome C revealed a pro-apoptotic effect of ulipristal. We also observed a reduced cellular proliferation, indicated by a decrease in Ki-67 expression and an anti-inflammatory effect, shown by a decrease in COX-2 expression after treatment with ulipristal.

• Authors: Carmen A Huniadi, Ovidiu L Pop, Tiberiu A Antal, Florin Stamatian
• Journal: European journal of obstetrics, gynecology, and reproductive biology (Eur J Obstet Gynecol Reprod Biol) Vol. 169 Issue 2 Pg. 360-5 (Jul 2013) ISSN: 1872-7654 [Electronic] Ireland
• PMID: 23619346 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Ki-67 Antigen
• Norpregnadienes
• bcl-2-Associated X Protein
• ulipristal
• Cytochromes c
• Cyclooxygenase 2
• Ptgs2 protein, rat

Topics

• Animals
• Cyclooxygenase 2 (biosynthesis, metabolism)
• Cytochromes c (antagonists & inhibitors, biosynthesis)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Endometriosis (drug therapy, enzymology, metabolism)
• Endometrium (drug effects, enzymology, metabolism)
• Female
• Ki-67 Antigen (biosynthesis, metabolism)
• Norpregnadienes (pharmacology, therapeutic use)
• Random Allocation
• Rats
• Rats, Wistar
• bcl-2-Associated X Protein (antagonists & inhibitors, biosynthesis)