Mitochonic acid-5 ameliorates chlorhexidine gluconate-induced peritoneal fibrosis in mice

Hiro Inoue, Kenta Torigoe, Miki Torigoe, Kumiko Muta, Yoko Obata, Takehiro Suzuki, Chitose Suzuki, Takaaki Abe, Takehiko Koji, Hiroshi Mukae, Tomoya Nishino

Research output: Contribution to journalArticlepeer-review

Abstract

Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis, attributable to inflammation and mitochondrial dysfunction. Mitochonic acid-5 (MA-5), an indole-3-acetic acid derivative, improves mitochondrial dysfunction and has therapeutic potential against various diseases including kidney diseases. However, whether MA-5 is effective against peritoneal fibrosis remains unclear. Therefore, we investigated the effect of MA-5 using a peritoneal fibrosis mouse model. Peritoneal fibrosis was induced in C57BL/6 mice via intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 3 weeks. MA-5 was administered daily by oral gavage. The mice were divided into control, MA-5, CG, and CG + MA-5 groups. Following treatment, immunohistochemical analyses were performed. Fibrotic thickening of the parietal peritoneum induced by CG was substantially attenuated by MA-5. The number of α-smooth muscle actin-positive myofibroblasts, transforming growth factor β-positive cells, F4/80-positive macrophages, monocyte chemotactic protein 1-positive cells, and 4-hydroxy-2-nonenal-positive cells was considerably decreased. In addition, reduced ATP5a1-positive and uncoupling protein 2-positive cells in the CG group were notably increased by MA-5. MA-5 may ameliorate peritoneal fibrosis by suppressing macrophage infiltration and oxidative stress, thus restoring mitochondrial function. Overall, MA-5 has therapeutic potential against peritoneal fibrosis.

Original languageEnglish
JournalMedical Molecular Morphology
DOIs
Publication statusAccepted/In press - 2021
Externally publishedYes

Keywords

  • Chlorhexidine gluconate
  • Mitochonic acid-5
  • Peritoneal dialysis
  • Peritoneal fibrosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology

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