Oral adsorbent AST-120 ameliorates gut environment and protects against the progression of renal impairment in CKD rats

Ayumi Yoshifuji, Shu Wakino, Junichiro Irie, Ayumi Matsui, Kazuhiro Hasegawa, Hirobumi Tokuyama, Koichi Hayashi, Hiroshi Itoh

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Oral charcoal adsorbent AST-120 (AST) is reported to ameliorate renal dysfunction by the absorption of toxic substance in the gut. Recent study revealed that, in CKD, gut environment is disturbed including the decrease in tight junctions and Lactobacillus (Lact). In this study, we examined whether AST improves the renal dysfunction through gut environment. Method: Six-week-old spontaneously hypertensive rats (SHR) were rendered CKD by 5/6th nephrectomy (Nx). SHRs were divided into SHR (Sham), SHR with Nx (Nx), and Nx given AST (Nx + AST) (n = 10, each). After 12 weeks, rats were killed and biochemical parameters were explored. The gut flora was analyzed. Furthermore, gut molecular changes in tight junctions and toll-like receptors were examined. We also investigated the effects of the combination therapy with AST and Lact. Results: The increase in serum urea nitrogen and urinary protein excretion in Nx was restored in Nx + AST. The increased renal glomerulosclerosis in Nx was ameliorated in Nx + AST. Increases in serum uremic toxins and IL-6 in Nx were ameliorated in Nx + AST. The gut flora analysis revealed that the decrease in Lact in Nx was restored in Nx + AST. The downregulation in the tight junction and TLR2 in Nx was mitigated by AST. However, combination therapy failed to exhibit additional effects. Conclusion: AST ameliorated renal function with the restoration of Lact and tight junction through TLR pathway, which would mitigate systemic inflammation and contributed to their renoprotective effects. Our study provides a novel mechanism of the renoprotective effects by AST.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalClinical and Experimental Nephrology
DOIs
Publication statusAccepted/In press - 2018 Apr 19

Fingerprint

Tight Junctions
Lactobacillus
Inbred SHR Rats
Kidney
Poisons
Toll-Like Receptors
Charcoal
Nephrectomy
Serum
Urea
Interleukin-6
Nitrogen
Down-Regulation
Inflammation
AST 120
Therapeutics
Proteins
Gastrointestinal Microbiome

Keywords

  • CKD
  • Microbiota
  • Tight junction
  • Toll-like receptor
  • Uremic toxin

ASJC Scopus subject areas

  • Physiology
  • Nephrology
  • Physiology (medical)

Cite this

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title = "Oral adsorbent AST-120 ameliorates gut environment and protects against the progression of renal impairment in CKD rats",
abstract = "Background: Oral charcoal adsorbent AST-120 (AST) is reported to ameliorate renal dysfunction by the absorption of toxic substance in the gut. Recent study revealed that, in CKD, gut environment is disturbed including the decrease in tight junctions and Lactobacillus (Lact). In this study, we examined whether AST improves the renal dysfunction through gut environment. Method: Six-week-old spontaneously hypertensive rats (SHR) were rendered CKD by 5/6th nephrectomy (Nx). SHRs were divided into SHR (Sham), SHR with Nx (Nx), and Nx given AST (Nx + AST) (n = 10, each). After 12 weeks, rats were killed and biochemical parameters were explored. The gut flora was analyzed. Furthermore, gut molecular changes in tight junctions and toll-like receptors were examined. We also investigated the effects of the combination therapy with AST and Lact. Results: The increase in serum urea nitrogen and urinary protein excretion in Nx was restored in Nx + AST. The increased renal glomerulosclerosis in Nx was ameliorated in Nx + AST. Increases in serum uremic toxins and IL-6 in Nx were ameliorated in Nx + AST. The gut flora analysis revealed that the decrease in Lact in Nx was restored in Nx + AST. The downregulation in the tight junction and TLR2 in Nx was mitigated by AST. However, combination therapy failed to exhibit additional effects. Conclusion: AST ameliorated renal function with the restoration of Lact and tight junction through TLR pathway, which would mitigate systemic inflammation and contributed to their renoprotective effects. Our study provides a novel mechanism of the renoprotective effects by AST.",
keywords = "CKD, Microbiota, Tight junction, Toll-like receptor, Uremic toxin",
author = "Ayumi Yoshifuji and Shu Wakino and Junichiro Irie and Ayumi Matsui and Kazuhiro Hasegawa and Hirobumi Tokuyama and Koichi Hayashi and Hiroshi Itoh",
year = "2018",
month = "4",
day = "19",
doi = "10.1007/s10157-018-1577-z",
language = "English",
pages = "1--10",
journal = "Clinical and Experimental Nephrology",
issn = "1342-1751",
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}

TY - JOUR

T1 - Oral adsorbent AST-120 ameliorates gut environment and protects against the progression of renal impairment in CKD rats

AU - Yoshifuji, Ayumi

AU - Wakino, Shu

AU - Irie, Junichiro

AU - Matsui, Ayumi

AU - Hasegawa, Kazuhiro

AU - Tokuyama, Hirobumi

AU - Hayashi, Koichi

AU - Itoh, Hiroshi

PY - 2018/4/19

Y1 - 2018/4/19

N2 - Background: Oral charcoal adsorbent AST-120 (AST) is reported to ameliorate renal dysfunction by the absorption of toxic substance in the gut. Recent study revealed that, in CKD, gut environment is disturbed including the decrease in tight junctions and Lactobacillus (Lact). In this study, we examined whether AST improves the renal dysfunction through gut environment. Method: Six-week-old spontaneously hypertensive rats (SHR) were rendered CKD by 5/6th nephrectomy (Nx). SHRs were divided into SHR (Sham), SHR with Nx (Nx), and Nx given AST (Nx + AST) (n = 10, each). After 12 weeks, rats were killed and biochemical parameters were explored. The gut flora was analyzed. Furthermore, gut molecular changes in tight junctions and toll-like receptors were examined. We also investigated the effects of the combination therapy with AST and Lact. Results: The increase in serum urea nitrogen and urinary protein excretion in Nx was restored in Nx + AST. The increased renal glomerulosclerosis in Nx was ameliorated in Nx + AST. Increases in serum uremic toxins and IL-6 in Nx were ameliorated in Nx + AST. The gut flora analysis revealed that the decrease in Lact in Nx was restored in Nx + AST. The downregulation in the tight junction and TLR2 in Nx was mitigated by AST. However, combination therapy failed to exhibit additional effects. Conclusion: AST ameliorated renal function with the restoration of Lact and tight junction through TLR pathway, which would mitigate systemic inflammation and contributed to their renoprotective effects. Our study provides a novel mechanism of the renoprotective effects by AST.

AB - Background: Oral charcoal adsorbent AST-120 (AST) is reported to ameliorate renal dysfunction by the absorption of toxic substance in the gut. Recent study revealed that, in CKD, gut environment is disturbed including the decrease in tight junctions and Lactobacillus (Lact). In this study, we examined whether AST improves the renal dysfunction through gut environment. Method: Six-week-old spontaneously hypertensive rats (SHR) were rendered CKD by 5/6th nephrectomy (Nx). SHRs were divided into SHR (Sham), SHR with Nx (Nx), and Nx given AST (Nx + AST) (n = 10, each). After 12 weeks, rats were killed and biochemical parameters were explored. The gut flora was analyzed. Furthermore, gut molecular changes in tight junctions and toll-like receptors were examined. We also investigated the effects of the combination therapy with AST and Lact. Results: The increase in serum urea nitrogen and urinary protein excretion in Nx was restored in Nx + AST. The increased renal glomerulosclerosis in Nx was ameliorated in Nx + AST. Increases in serum uremic toxins and IL-6 in Nx were ameliorated in Nx + AST. The gut flora analysis revealed that the decrease in Lact in Nx was restored in Nx + AST. The downregulation in the tight junction and TLR2 in Nx was mitigated by AST. However, combination therapy failed to exhibit additional effects. Conclusion: AST ameliorated renal function with the restoration of Lact and tight junction through TLR pathway, which would mitigate systemic inflammation and contributed to their renoprotective effects. Our study provides a novel mechanism of the renoprotective effects by AST.

KW - CKD

KW - Microbiota

KW - Tight junction

KW - Toll-like receptor

KW - Uremic toxin

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U2 - 10.1007/s10157-018-1577-z

DO - 10.1007/s10157-018-1577-z

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JO - Clinical and Experimental Nephrology

JF - Clinical and Experimental Nephrology

SN - 1342-1751

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