OBJECTIVE: Indoxyl sulfate (IS), a uremic toxin, is a risk factor for progression of chronic kidney disease (CKD). AST-120 reduces serum IS and delays the progression of CKD. This study aimed to examine whether AST-120 inhibits epithelial-to-mesenchymal transition (EMT) in the kidneys of CKD rats. METHODS: CKD rats were produced by 5/6 nephrectomy and were divided into 2 groups: (1) CKD rats and (2) AST-120-treated CKD rats at a dosage of 4 g/kg body weight/day. After 10 weeks, their kidneys were excised for histological and immunohistochemical analysis. EMT was evaluated by immunohistochemistry of zonula occludens (ZO-1), an epithelial marker, and alpha-smooth muscle actin (α-SMA), a mesenchymal marker. Interstitial fibrosis was evaluated by Masson's trichrome staining. RESULTS: CKD rats showed reduced expression of ZO-1 and enhanced expression of α-SMA as compared with normal rats. Administration of AST-120 to CKD rats increased expression of ZO-1 and decreased expression of α-SMA as compared with CKD rats. Further, CKD rats showed enhanced extent of interstitial fibrosis as compared with normal rats, and administration of AST-120 to CKD rats ameliorated interstitial fibrosis. CKD rats showed increased serum level of IS as compared with normal rats, whereas administration of AST-120 to CKD rats decreased both serum and urine levels of IS. CONCLUSION: We conclude that AST-120 ameliorated EMT and interstitial fibrosis in the kidneys of CKD rats, probably by alleviating IS overload on the kidneys.
OBJECTIVE:Indoxyl sulfate (IS), a uremic toxin, is a risk factor for progression of chronic kidney disease (CKD). AST-120 reduces serum IS and delays the progression of CKD. This study aimed to examine whether AST-120 inhibits epithelial-to-mesenchymal transition (EMT) in the kidneys of CKD rats. METHODS: CKD rats were produced by 5/6 nephrectomy and were divided into 2 groups: (1) CKD rats and (2) AST-120-treated CKD rats at a dosage of 4 g/kg body weight/day. After 10 weeks, their kidneys were excised for histological and immunohistochemical analysis. EMT was evaluated by immunohistochemistry of zonula occludens (ZO-1), an epithelial marker, and alpha-smooth muscle actin (α-SMA), a mesenchymal marker. Interstitial fibrosis was evaluated by Masson's trichrome staining. RESULTS: CKD rats showed reduced expression of ZO-1 and enhanced expression of α-SMA as compared with normal rats. Administration of AST-120 to CKD rats increased expression of ZO-1 and decreased expression of α-SMA as compared with CKD rats. Further, CKD rats showed enhanced extent of interstitial fibrosis as compared with normal rats, and administration of AST-120 to CKD rats ameliorated interstitial fibrosis. CKD rats showed increased serum level of IS as compared with normal rats, whereas administration of AST-120 to CKD rats decreased both serum and urine levels of IS. CONCLUSION: We conclude that AST-120 ameliorated EMT and interstitial fibrosis in the kidneys of CKD rats, probably by alleviating IS overload on the kidneys.
Authors: Susan R Sandeman; Carol A Howell; Gary J Phillips; Yishan Zheng; Guy Standen; Robert Pletzenauer; Andrew Davenport; Kolitha Basnayake; Owen Boyd; Stephen Holt; Sergey V Mikhalovsky Journal: J Mater Sci Mater Med Date: 2014-02-27 Impact factor: 3.896