The kampo medicine Daikenchuto inhibits peritoneal fibrosis in mice.
Long-term peritoneal dialysis therapy causes inflammation and histological changes in the peritoneal membrane. Inflammation generally activates fibroblasts and results in fibroblast-myofibroblast differentiation. Heat-shock protein 47 (HSP 47), a collagen-specific molecular chaperone, is localized in myofibroblasts and is involved in the progression of peritoneal fibrosis. Daikenchuto (DKT), a Kampo medicine, is used to prevent postoperative colon adhesion. It inhibits inflammation and HSP 47 expression in the gastrointestinal tract. We examined the effect of DKT on chlorhexidine gluconate (CG)-induced peritoneal fibrosis in mice injected with 0.1% CG dissolved in 15% ethanol. DKT was dissolved in the drinking water. Histological changes were assessed using Masson trichrome staining. Cells expressing α-smooth muscle actin (α-SMA), HSP 47, phospho-Smad 2/3, F4/80, and monocyte chemotactic protein-1 were examined immunohistochemically. Compared with the control group, the peritoneal tissues of the CG group were markedly thickened, and the number of cells expressing α-SMA, HSP 47, phospho-Smad 2/3, F4/80, and monocyte chemotactic protein-1 was significantly increased. However, these changes were inhibited in the DKT-treated group. These results indicate that DKT can prevent peritoneal fibrosis by inhibiting inflammation and HSP 47 expression.
Second Department of Internal Medicine, Nagasaki University School of Medicine.
Mineaki
M
Kitamura
Tomoya
T
Nishino
Yoko
Y
Obata
Satoru
S
Oka
Shinichi
S
Abe
Kumiko
K
Muta
Yoshiyuki
Y
Ozono
Takehiko
T
Koji
Shigeru
S
Kohno
D000199:Actins / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D002710:Chlorhexidine / Q000031:analogs & derivatives; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D020835:Medicine, Kampo; D008813:Mice, Inbred ICR; D005894:Panax; D056627:Peritoneal Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D032106:Zanthoxylum; D030521:Zingiberaceae
C558396:Acta2 protein, mouse; D000199:Actins; D000943:Antigens, Differentiation; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D050958:HSP47 Heat-Shock Proteins; D010936:Plant Extracts; C494661:Serpinh1 protein, mouse; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016212:Transforming Growth Factor beta; C121414:dai-kenchu-to; C036763:monocyte-macrophage differentiation antigen; C010882:chlorhexidine gluconate; D002710:Chlorhexidine