Doxycycline causes regression of endometriotic implants: a rat model.
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.
Akkaya
Pinar
P
Obstetrics and Gynecology, Baskent University School of Medicine, Kubilay Sok no. 36 Maltepe, 06570 Ankara, Turkey.
Onalan
Gogsen
G
Haberal
Nihan
N
Bayraktar
Nilufer
N
Mülayim
Baris
B
Zeyneloglu
Hulusi B
HB
D000818:Animals; D004318:Doxycycline / Q000627:therapeutic use*; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology; D004717:Endometrium / Q000637:transplantation; D005260:Female; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D016729:Leuprolide / Q000627:therapeutic use; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D015850:Interleukin-6; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D016729:Leuprolide; D004318:Doxycycline