Efficacy of Cyclosporin A and Tacrolimus in The Treatment of Endometriosis of Rats

Abstract

Background and Aims

The molecular and cellular mechanisms underlying endometriosis are still under investigation. Cyclophilin A (CypA) is an inflammatory marker secreted by various types of cells in an inflammatory condition. During inflammation, CypA exacerbates the inflammatory response by activating calcineurin signaling, which increases cytokine secretion and tissue degradation in the inflammatory region. This study investigated the effect of inhibiting calcineurin signaling in treating endometriosis in rats.

Methods

Thirty-two albino Wistar rats were used in this study. All rats were divided into three groups: cyclosporin A (n = 10), tacrolimus (n = 10) and a control group (n = 12). The cyclosporin A (CsA) group received two intraperitoneal doses two weeks apart, and the tacrolimus group received the same two doses intravenously, also two weeks apart. All studies lasted eight weeks. The processed endometrial tissues were cut in half and embedded in paraffin. Histological sections (5 µm) were stained with Ki-67, Bcl-2, caspase-3 and VEGF.

Results

The endometriotic focus size was 204.7 ± 153.4 mm³, 71.9 ± 85.4 mm³, and 30.6 ± 36.7 mm³ in the control, CsA, and tacrolimus groups, respectively. Compared to the control group, the endometriotic focus size was smaller in the CsA and tacrolimus groups (p = 0.002). Microscopically, Ki-67 (p = 0.010) and VEGF (p = 0.007) immunoreactivity were lower in the CsA and tacrolimus groups than in controls.

Conclusions

The inhibition of calcineurin signaling with CsA or tacrolimus treatment causes regression of the endometriotic focus by decreasing endometriotic cell proliferation and angiogenesis in ectopic endometriotic tissue.