Peritoneal macrophage depletion by liposomal bisphosphonate attenuates endometriosis in the rat model

E Haber, Elran Haber, H D Danenberg, Haim Danenberg, Nickolay Koroukhov, N Koroukhov, R Ron-El, Gershon Golomb, G Golomb, M Schachter
Human Reproduction · 2008 · vol. 24(2) , pp. 398–407 · doi:10.1093/humrep/den375 · PMID:18948309 · W2106567800
article OA: bronze CC0 ⤵ 46 in-corpus citations
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Intraperitoneal liposomal alendronate depleted peritoneal macrophages and inhibited endometriosis lesion initiation and growth in a rat model in a dose-dependent manner.

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Abstract

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.

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Condition tags

endometriosis

MeSH descriptors

Alendronate Bone Density Conservation Agents Endometriosis Macrophages, Peritoneal Alendronate Alendronate Alendronate Animals Bone Density Conservation Agents Bone Density Conservation Agents Bone Density Conservation Agents Chemokine CCL2 Chemokine CCL2 Cytokines Cytokines Disease Models, Animal Dose-Response Relationship, Drug Endometriosis Endometriosis Female

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