Oral Administration of Pentoxifylline Reduces Endometriosis-Like Lesions in a Nude Mouse Model

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Oral administration of pentoxifylline significantly reduced the volume and area of endometriosis-like lesions, vascularization, and cytokine levels in nude mice.

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This study assessed whether oral pentoxifylline reduces endometriosis-like lesions in a heterologous nude mouse model by implanting human endometrial tissue from five women into 30 mice and treating them for 28 days with saline (control) or pentoxifylline at 100 or 200 mg/kg/day. Macroscopic and histologic quantification showed a dose-dependent reduction in lesion number and, specifically, significantly lower lesion volume and mean endometriosis area in the 200 mg/kg/day group versus the other groups. The authors also report reduced vascularization and lower cytokine levels in peritoneal fluid after treatment. A key limitation is the small human tissue sample size (n=5) and the use of a mouse model that used implanted human tissue rather than studying spontaneous or genetically driven disease. This paper is centrally about endometriosis — pentoxifylline’s oral immunomodulatory effects on endometriosis-like lesions in nude mice.

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Abstract

IntroductionRecent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model.Study designHuman endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured.ResultsMacroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm3 vs 276.75 ± 94.30 mm3 and 145.33 ± 38.20 mm3, respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm2) versus group 2 (1.35 ± 0.43 mm2) and control (2.84 ± 0.60 mm2; P = .001). Vascularization and cytokine levels were also reduced posttreatment.ConclusionOur results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required.
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Abstract

Introduction: Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model. Study Design: Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group I); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured. Results: Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm3 vs 276.75 ±94.30 mm3 and 145.33 ± 38.20 mm3, respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm2) versus group 2 (1.35 ± 0.43 mm2) and control (2.84 ± 0.60 mm2; P = .001). Vascularization and cytokine levels were also reduced posttreatment. Conclusion: Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required. Similar content being viewed by others

References

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Sci. 24, 911–918 (2017). https://doi.org/10.1177/1933719116673198 Published: Issue date: DOI: https://doi.org/10.1177/1933719116673198

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endometriosis

MeSH descriptors

Endometriosis Endometrium Pentoxifylline Vasodilator Agents Administration, Oral Animals Disease Models, Animal Endometriosis Endometriosis Endometrium Endometrium Female Mice Mice, Nude Neovascularization, Pathologic Neovascularization, Pathologic Neovascularization, Pathologic Pentoxifylline Pentoxifylline Treatment Outcome

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chemicals 4
pentoxifylline pentoxifylline pentoxifylline pentoxifylline
organisms 6
transgenic mice mus sp. human noordeloos 2009062 mus sp. multicellular animals

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