PMID- 14654984
OWN - NLM
STAT- MEDLINE
DCOM- 20040316
LR  - 20061115
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 13
IP  - 1
DP  - 2004 Jan
TI  - Possible involvement of nuclear factor-kappaB inhibition in the renal protective 
      effect of oral adsorbent AST-120 in a rat model of chronic renal failure.
PG  - 133-8
AB  - Oral adsorbent, AST-120 removes uremic toxins (such as indoxyl sulfate) and 
      retards the progression of chronic renal failure (CRF). However, its mechanism of 
      action has not been precisely clarified. Since indoxyl sulfate elicits renal 
      tubular nuclear factor-kappaB (NF-kappaB) activation in vitro, the present 
      experiments were conducted to elucidate the involvement of NF-kappaB in the 
      beneficial effects of AST-120 using rats with 3/4 nephrectomy, a model of 
      early-stage CRF. Daily administration of AST-120 was started at 6 weeks after 3/4 
      nephrectomy and continued for 18 weeks. Sham-operated rats, untreated CRF rats 
      and AST-120-treated CRF rats were compared for NF-kappaB DNA-binding activity, 
      gene expression and renal histology. Systolic blood pressure was increased in CRF 
      rats, and this increase was not affected by AST-120. Blood urea nitrogen, serum 
      creatinine and urinary protein were increased in CRF rats. Although AST-120 
      attenuated these increases, it did not do so to a statistically significant 
      extent. Indoxyl sulfate, which was accumulated in serum of CRF rats, was 
      significantly eliminated by AST-120. Renal cortical NF-kappaB DNA-binding 
      activity was increased in CRF rats. AST-120 significantly inhibited this 
      increase. Monocyte/macrophage infiltration and increased monocyte chemoattractant 
      protein-1 (MCP-1) mRNA observed in CRF rats were attenuated by AST-120. 
      Furthermore, AST-120 significantly blocked renal fibrosis with concomitant 
      inhibition of transforming growth factor beta1 (TGF-beta1) gene expression. It 
      appeared that AST-120 reduced NF-kappaB activation and possibly the activity of 
      NF-kappaB-dependent pathways of interstitial inflammation including MCP-1 
      expression and macrophage infiltration. The anti-inflammatory effect of AST-120 
      mediated via inhibition of NF-kappaB is a possible mechanism by which AST-120 
      retards the progression of renal fibrosis in CRF.
FAU - Komiya, Toshiyuki
AU  - Komiya T
AD  - Department of Nephrology, Osaka City University Medical School, 1-4-3 Asahimachi, 
      Abeno-ku Osaka 545-8585, Japan.
FAU - Miura, Katsuyuki
AU  - Miura K
FAU - Tsukamoto, Jin
AU  - Tsukamoto J
FAU - Okamura, Mikio
AU  - Okamura M
FAU - Tamada, Satoshi
AU  - Tamada S
FAU - Asai, Toshihiro
AU  - Asai T
FAU - Tashiro, Koichiro
AU  - Tashiro K
FAU - Kuwabara, Nobuyuki
AU  - Kuwabara N
FAU - Iwao, Hiroshi
AU  - Iwao H
FAU - Yoshikawa, Junichi
AU  - Yoshikawa J
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Oxides)
RN  - 0 (RNA, Messenger)
RN  - 7440-44-0 (Carbon)
RN  - 90597-58-3 (AST 120)
SB  - IM
MH  - Animals
MH  - Carbon/*pharmacology
MH  - Chemokine CCL2/biosynthesis/genetics
MH  - Disease Models, Animal
MH  - Electrophoretic Mobility Shift Assay
MH  - Fibrosis
MH  - Immunohistochemistry
MH  - Kidney Cortex/drug effects/pathology
MH  - Kidney Failure, Chronic/*drug therapy
MH  - Macrophages/drug effects
MH  - Monocytes/drug effects
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Oxides/*pharmacology
MH  - RNA, Messenger/metabolism
MH  - Rats
EDAT- 2003/12/05 05:00
MHDA- 2004/03/17 05:00
CRDT- 2003/12/05 05:00
PHST- 2003/12/05 05:00 [pubmed]
PHST- 2004/03/17 05:00 [medline]
PHST- 2003/12/05 05:00 [entrez]
PST - ppublish
SO  - Int J Mol Med. 2004 Jan;13(1):133-8.