Journal Article

Effects of liposome-encapsulated clodronate on chlorhexidine gluconate-induced peritoneal fibrosis in rats

Taketoshi Kushiyama, Takashi Oda, Muneharu Yamada, Keishi Higashi, Kojiro Yamamoto, Naoki Oshima, Yutaka Sakurai, Soichiro Miura and Hiroo Kumagai

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 26, issue 10, pages 3143-3154
Published in print October 2011 | ISSN: 0931-0509
Published online March 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr068
Effects of liposome-encapsulated clodronate on chlorhexidine gluconate-induced peritoneal fibrosis in rats

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Background. Long-term peritoneal dialysis (PD) causes morphologic and functional changes in the peritoneum that hamper the continuation of PD therapy. Because macrophages play important roles in the development of peritoneal fibrosis and liposome-encapsulated clodronate (LC) induces macrophage apoptosis, we examined the effect of LC on chlorhexidine gluconate (CG)-induced peritoneal fibrosis in rats.

Methods. Fifty Sprague–Dawley rats were randomly allocated into five groups of 10 receiving intraperitoneal (i.p.) injections (1.5 mL/100 g) of either 0.1% CG (four groups) or vehicle (one group) three times a week. Three of the CG-treated groups also received intravenous injections of clodronate twice a week: 10 mg of LC, 20 mg of LC or 20 mg of unencapsulated clodronate (UC20). Twenty-one days after the first i.p. injection, the rats were sacrificed and the parietal peritoneum was harvested.

Results. The number of peritoneal macrophages in the rats given clodronate was significantly smaller than that in rats not given clodronate (92.0 ± 4.6 cells per field). It was 54.1 ± 3.2 cells per field in the group given 20 mg UC, 43.2 ± 5.2 cells per field in the group given 10 mg LC and 27.2 ± 2.8 cells per field in the group given 20 mg LC. This decrease in macrophage number was paralleled by decreases in peritoneal thickening, in the number of mesothelial cells staining positive for cytokeratin and α-smooth muscle actin and in messenger RNA expression for transforming growth factor-β1 and collagen types I and III.

Conclusions. These data suggest that macrophages play a critical role in the development of peritoneal fibrosis and that LC may be useful for treating peritoneal fibrosis in PD patients.

Keywords: continuous ambulatory peritoneal dialysis; epithelial-mesenchymal transition; liposome-encapsulated clodronate; macrophages; peritoneal fibrosis

Journal Article.  5077 words.  Illustrated.

Subjects: Nephrology

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