P1226MITOCHONIC ACID 5 (MA-5) AMELIORATES CG-INDUCED PERITONEAL FIBROSIS IN MICE

Abstract

Abstract Background and Aims 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 a variety of disease including fibrosis in several organs. Recently, mitochonic acid 5 (MA-5) 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 model in mice. Method Peritoneal fibrosis was induced by intraperitoneal injection of chlorhexidine gluconate (CG) every other day for 3 weeks in C57/BL6 mice. MA-5 was administered at 2 mg/kg by gavage every day from the initiation of CG injection. 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 (MCP1), α-smooth muscle actin (α-SMA), and transforming growth factor-β (TGF-β) were evaluated by immunohistochemistry. Results The fibrotic thickening of parietal peritoneum was significantly attenuated in MA-5 treated mice compared with control mice (the thickness of submesothelial area: 100.24 +/- 13.67 vs 54.78 +/- 7.43 μm (p<0.05)). The numbers of TGF-β positive cells, α-SMA positive cells, MCP1 positive cells and infiltrating macrophages were significantly decreased in MA-5 treated mice than those in control mice. Conclusion These results suggest that MA-5 may have a therapeutic potential in the progression of peritoneal fibrosis as well as kidney disease models.