Doxycycline causes regression of endometriotic implants: a rat model

Akkaya P, P. Akkaya, Pinar Akkaya, Onalan G, Gogsen Onalan, Göğşen Önalan, Nihan Haberal, Haberal N, Nilüfer Bayraktar, Nilufer Bayraktar, Barış Mülayim, Mülayim B, Baris Mülayim, Hulusi Bülent Zeyneloğlu, Hulusi B. Zeyneloglu
Human Reproduction · 2009 · vol. 24(8) , pp. 1900–1908 · doi:10.1093/humrep/dep106 · PMID:19401321 · W2154893338
Lab / animal OA: closed CC0 ⤵ 12 in-corpus citations
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Doxycycline treatment significantly reduced endometriotic implant size and MMP expression in a rat model, with low-dose Dox also decreasing IL-6 levels.

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Abstract

BACKGROUND: Doxycycline (Dox) has a number of non-antibiotic properties. One of them is the inhibition of matrix metalloproteinase (MMP) activity. The aim of this study was to assess the effects of Dox in a rat endometriosis model. METHODS: Endometriosis was surgically induced in 40 rats by transplanting of endometrial tissue. After 3 weeks, repeat laparotomies were performed to check the implants and the animals were randomized into four groups: Group I, low-dose Dox (5 mg/kg/day); Group II, high-dose Dox (40 mg/kg/day); Group III, leuprolide acetate 1 mg/kg single dose, s.c.; and Group VI (controls), no medication. The treatment, initiated on the day of surgery and continuing for 3 weeks, was administered to the study groups. Three weeks later, the rats were euthanized and the implants were evaluated morphologically and histologically for immunoreactivity of MMP-2 and -9, and interleukin-6 (IL-6) concentration in the peritoneal fluid was assayed. RESULTS: Treatment with leuprolide acetate, or high-dose or low-dose Dox caused significant decreases in the implant areas compared with the controls (P = 0.03, P = 0.006, and P = 0.001, respectively). IL-6 levels in peritoneal fluid decreased in Group I (P = 0.02) and Group III (P < 0.05). MMP H scores were significantly lower in the group that received low-dose Dox in both epithelial and stromal MMP-2 and -9 immunostaining when compared with the control group [P = 0.048, P = 0.002, P = 0.007 and P = 0.002, respectively, MMP-2 (epithelia), MMP-2 (stroma), MMP-9 (epithelia) and MMP-9 (stroma)]. CONCLUSIONS: Low-dose Dox caused regression of endometriosis in this experimental rat model.

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Condition tags

endometriosis

MeSH descriptors

Doxycycline Endometriosis Animals Animals Doxycycline Doxycycline Endometriosis Endometriosis Endometriosis Endometrium Endometrium Endometrium Female Female Immunohistochemistry Immunohistochemistry Interleukin-6 Interleukin-6 Interleukin-6 Leuprolide

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