PMID- 18948309
OWN - NLM
STAT- MEDLINE
DCOM- 20090415
LR  - 20131121
IS  - 1460-2350 (Electronic)
IS  - 0268-1161 (Linking)
VI  - 24
IP  - 2
DP  - 2009 Feb
TI  - Peritoneal macrophage depletion by liposomal bisphosphonate attenuates 
      endometriosis in the rat model.
PG  - 398-407
LID - 10.1093/humrep/den375 [doi]
AB  - BACKGROUND: Activation of macrophages is central to the implantation of 
      endometriosis (EM). We examined the hypothesis that macrophage depletion by 
      intraperitoneal (IP) injection of liposomal alendronate (LA) could result in EM 
      attenuation in a rat model, thus supporting the notion of the pivotal role of 
      macrophages in EM pathology. METHODS: In this study, 90 rats were subjected to an 
      EM model and were divided randomly into seven groups: five groups were treated by 
      4x once-weekly IP injections of LA (0.02, 0.1, 1, 5 or 10 mg/kg) and the other 
      two groups received saline injections (control) or empty liposomes. Sham-operated 
      rats also received empty liposomes. Depletion of circulating monocytes was 
      determined by flow cytometry analyzes of blood specimens. Four weeks after the 
      initial surgery, the number, size and weight of implants were recorded, adhesions 
      were graded, macrophage infiltration was assessed and the peritoneal fluid was 
      analyzed for monocyte chemotactic protein 1 (MCP-1) and tumor necrosis factor 
      alpha (TNFalpha). RESULTS: Monocyte depletion following IP LA administration 
      resulted in an inhibitory effect on the initiation and growth of EM implants, as 
      expressed by implantation rate, adhesion scoring, implants' size and weight (>0.1 
      mg/kg LA, P < 0.05). Reduced numbers of infiltrating macrophages were observed in 
      implants of the 1 mg/kg LA group. Peritoneal fluid MCP-1 levels were negatively 
      correlated with LA dose (P < 0.001), whereas no significant correlation could be 
      found for TNFalpha. CONCLUSIONS: Macrophage depletion using IP LA has been shown 
      to effectively inhibit the initiation and growth of EM implants, in a rat EM 
      model. The clear dose-response effect may be viewed as a confirmation of the 
      validity of the concept and encourages further study.
FAU - Haber, E
AU  - Haber E
AD  - Faculty of Medicine, Department of Pharmaceutics, School of Pharmacy, The Hebrew 
      University of Jerusalem, PO Box 12065, Jerusalem 91120, Israel.
FAU - Danenberg, H D
AU  - Danenberg HD
FAU - Koroukhov, N
AU  - Koroukhov N
FAU - Ron-El, R
AU  - Ron-El R
FAU - Golomb, G
AU  - Golomb G
FAU - Schachter, M
AU  - Schachter M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081023
PL  - England
TA  - Hum Reprod
JT  - Human reproduction (Oxford, England)
JID - 8701199
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Liposomes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - X1J18R4W8P (Alendronate)
SB  - IM
MH  - Alendronate/administration & dosage/pharmacology/*therapeutic use
MH  - Animals
MH  - Bone Density Conservation Agents/administration & 
      dosage/pharmacology/*therapeutic use
MH  - Chemokine CCL2/analysis
MH  - Cytokines/physiology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Endometriosis/*drug therapy/pathology
MH  - Female
MH  - Flow Cytometry
MH  - Immunohistochemistry
MH  - Injections, Intraperitoneal
MH  - Liposomes
MH  - Macrophages, Peritoneal/*drug effects
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Tumor Necrosis Factor-alpha/analysis
EDAT- 2008/10/25 09:00
MHDA- 2009/04/16 09:00
CRDT- 2008/10/25 09:00
PHST- 2008/10/25 09:00 [pubmed]
PHST- 2009/04/16 09:00 [medline]
PHST- 2008/10/25 09:00 [entrez]
AID - den375 [pii]
AID - 10.1093/humrep/den375 [doi]
PST - ppublish
SO  - Hum Reprod. 2009 Feb;24(2):398-407. doi: 10.1093/humrep/den375. Epub 2008 Oct 23.