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Abstract: PO1323

Mitochonic Acid 5 Alleviates Chlorhexidine Gluconate-Induced Peritoneal Fibrosis in Mice

Session Information

Category: Dialysis

  • 703 Dialysis: Peritoneal Dialysis

Authors

  • Inoue, Hiro, Department of Nephrology, Nasasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • Obata, Yoko, Department of Nephrology, Nasasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • Suzuki, Takehiro, Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
  • Torigoe, Miki, Department of Nephrology, Nasasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • Torigoe, Kenta, Department of Nephrology, Nasasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • Muta, Kumiko, Department of Nephrology, Nasasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • Suzuki, Chitose, Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
  • Abe, Takaaki, Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
  • Koji, Takehiko, Department of Histology and Cell Biology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • Nishino, Tomoya, Department of Nephrology, Nasasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
Background

Peritoneal fibrosis is one of important complications induced by long-term peritoneal dialysis. Mitochondrial dysfunction causes an increase of oxidative stress and depletion of ATP. Thus, it may be associated with fibrosis and other diseases in several organs. Recently, mitochonic acid 5 (MA-5), which is a derivative of the plant hormone indole-3-acetic acid, was synthesized and its therapeutic potential for mitochondrial dysfunction in kidney disease models has been reported. In this study, we investigated the effect of MA-5 for peritoneal fibrosis in mice.

Methods

Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 3 weeks in C57BL/6 mice. MA-5 was administered at 2 mg/kg by gavage every day. Control mice received only a vehicle (distilled water). After 3 weeks of treatment, the animals were sacrificed and the peritoneal tissues were collected. The peritoneal sections were stained with Masson’s trichrome for light microscopic examination and the fibrotic thickening of parietal peritoneum was measured on the randomly selected different regions on each section. The expressions of F4/80, which is a marker of macrophages, monocyte chemotactic protein-1 (MCP-1), transforming growth factor-β (TGF-β) and α-smooth muscle actin (α-SMA) were examined by immunohistochemistry.

Results

Compared with control mice, the fibrotic thickening of parietal peritoneum was significantly attenuated in MA-5 treated mice (the thickness of submesothelial area: 100.24 ± 13.67 vs 54.78 ± 7.43 μm (p<0.05)) with the lower number of TGF-β positive cells and α-SMA positive myofibroblasts. The infiltration of macrophages was markedly reduced with the decreased expression of MCP-1 in MA-5 treated mice than those in control mice.

Conclusion

Our results suggest that MA-5 alleviates peritoneal fibrosis with the reduction of macrophages infiltration. Thus, MA-5 may have a therapeutic potential in the progression of peritoneal fibrosis as well as kidney disease models.