Effect of the immunomodulator leflunomide on the induction of endometriosis in an experimental rat model

Aytan, Hakan; Caglar, P.; Uygur, Dilek; Zergeroğlu, Sema; Batıoğlu, Sertaç

doi:10.1016/j.fertnstert.2006.07.1527

Cited by 21 publications

(13 citation statements)

References 24 publications

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“…We found that A771726 decreased endometriotic cell proliferation in vitro and that both A771726 and leflunomide controlled endometriosis progression in vivo in our murine model. Our results confirm a previous study by Aytan et al , who found that leflunomide can abrogate the development of endometriosis in an experimental rat model 39. In contrast with PD98059 and U0126, leflunomide is widely used in clinical practice and its efficacy and side‐effects are well known 40–42.…”

Section: Discussionsupporting

confidence: 91%

Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo

Ngô

Nicco

Leconte

et al. 2010

The Journal of Pathology

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Endometriosis affects 6-10% of women in their reproductive years, causing chronic pelvic pain and infertility. Its pathogenesis remains poorly understood and current treatments, based on hormonal therapy or surgery, are often insufficient. The purpose of our study was to investigate the role of the ERK pathway in the development of endometriosis and to test the effects of protein kinase inhibitors on the proliferation of endometriotic cells in vitro and in vivo. We studied ex vivo human endometrial and endometriotic cells in culture. Stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from patients with endometriosis and from patients without endometriosis. The ERK pathway was explored by western blot on cell lysates and by ELISA on total crushed specimens of endometrium. Cells in culture were treated with A771726, PD98059, and U0126. Human endometriotic lesions were implanted in nude mice. Mice were treated with A771726, leflunomide, PD98059, U0126 or PBS during 2 weeks before sacrifice and extraction of the endometriotic implants for histological examination. We found that the ERK pathway was significantly activated in endometriotic cells and in endometrial cells from patients with endometriosis compared to endometrial cells of control patients, both by ELISA and by western blot. This phenomenon was associated with an increased proliferation of endometriotic cells compared to endometrial cells. Treating endometriotic cells with A771726, PD98059 or U0126 abrogated the phosphorylation of ERK and significantly decreased the cellular proliferation in vitro. In vivo, A771726, leflunomide, PD98059, and U0126 controlled the growth of endometriotic implants in the mouse model of endometriosis. Our study shows that protein kinase inhibitors could be new candidates to treat endometriosis. However, further studies are needed to evaluate their effects and tolerability in humans.

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Section: Discussionsupporting

confidence: 91%

Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo

Ngô

Nicco

Leconte

et al. 2010

The Journal of Pathology

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“…Furthermore, peritoneal endometrial implants regressed following treatment with the immunomodulators infliximab and etanercept, with no change in VEGF level or immunoreactivity. Uygur et al . also reported that the immunomodulator leflunomide decreased endometriotic foci in two studies investigating the efficacy of leflunomide for endometriotic implant regression.…”

Section: Discussionmentioning

confidence: 94%

“…There are several treatment options for endometriosis. Gonadotropin‐releasing hormone (GnRH) analogs have demonstrated efficacy in experimental studies and are used in humans as a conventional treatment, and immunomodulators and aromatase inhibitors are newer treatment options that are gaining popularity . Several medications used in endometriosis treatment decrease vasculogenesis by reducing angiogenesis and decreasing VEGF expression and secretion .…”

Section: Discussionmentioning

confidence: 99%

Regression of experimental endometriotic implants in a rat model with the angiotensin II receptor blocker losartan

Çakmak

Çavuşoğlu

Ateş

et al. 2014

J of Obstet and Gynaecol

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“…Leflunomide, used mainly in rheumatoid arthritis, has antiinflammatory, antipyretic, and analgesic effects. At high doses, its active metabolite A77 1726 suppresses IL-1 and TNF-a production (43). Levamisole is currently used as an anthelminthic drug and as an adjuvant in the treatment of colorectal adenocarcinomas.…”

Section: Immunomodulatorsmentioning

confidence: 99%

“…Moreover, this molecule can stimulate the formation of antibodies to various antigens, enhance the cellular immune response provided by T cells, and potentiate monocyte, macrophage, and neutrophil functions (44). All these agents were shown to statistically significantly reduce the volume of endometriosis-like lesions, with regression of both glands and stroma, when compared with controls (41,(43)(44)(45). Their precise mechanisms of action in endometriosis are still unknown.…”

Section: Immunomodulatorsmentioning

confidence: 99%

Pharmacologic therapies in endometriosis: a systematic review

Soares¹,

Martínez-Varea

Hidalgo-Mora

et al. 2012

Fertility and Sterility

137

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Effect of the immunomodulator leflunomide on the induction of endometriosis in an experimental rat model

Cited by 21 publications

References 24 publications

Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo

Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo

Regression of experimental endometriotic implants in a rat model with the angiotensin II receptor blocker losartan

Pharmacologic therapies in endometriosis: a systematic review

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