講演・口頭発表等

2020年10月22日

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

Kidney Week 2020
  • Hiro Inoue
  • ,
  • Yoko Obata
  • ,
  • Takehiro Suzuki
  • ,
  • Miki Torigoe
  • ,
  • Kenta Torigoe
  • ,
  • Kumiko Muta
  • ,
  • Chitose Suzuki
  • ,
  • Takaaki Abe
  • ,
  • Takehiko Koji
  • ,
  • Tomoya Nishino

記述言語
英語
会議種別
ポスター発表

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.