Hum. Reprod. Advance Access originally published online on April 28, 2009
Human Reproduction 2009 24(8):1900-1908; doi:10.1093/humrep/dep106
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Doxycycline causes regression of endometriotic implants: a rat model

Mülayim11 Obstetrics and Gynecology, Baskent University School of Medicine, Kubilay Sok no. 36 Maltepe, 06570 Ankara, Turkey 2 Department of Pathology, Baskent University School of Medicine, Ankara, Turkey 3 Biochemistry Laboratories, Baskent University Hospital, Ankara, Turkey
4 Correspondence address. Fax: +90-312-2323912; E-mail: hulusi.zeyneloglu{at}gmail.com
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.
Key words: endometriosis/rat/doxycycline/MMP/treatment
Submitted on July 9, 2008; resubmitted on March 19, 2009; accepted on March 30, 2009.