Suppressed Serum and Urine Levels of Indoxyl Sulfate by Oral Sorbent in Experimental Uremic Rats

Niwa, Toshimitsu; Miyazaki, Takashi; Hashimoto, Naosumi; Hayashi, Hideo; Ise, Mikiko; Uehara, Yasuo; Maeda, Kenji

doi:10.1159/000168447

Cited by 53 publications

(49 citation statements)

References 6 publications

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“…Oral carbonaceous adsorbent, AST-120 (Kremezin ® ), removes uremic toxins by interfering with intestinal absorption of uremic toxins and their precursors (such as indole) (19) and retards the progression of CRF in uremic rats (20). Indoxyl sulfate has been shown to activate NF-κB in renal proximal tubular cells in vitro (21).…”

Section: Renal Protective Effect Of Oral Adsorbent Ast-120 and Nf-κbmentioning

confidence: 99%

Molecular Mechanisms and Therapeutic Strategies of Chronic Renal Injury: The Role of Nuclear Factor κB Activation in the Development of Renal Fibrosis

et al. 2006

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Abstract. Tubulointerstitial fibrosis is a common feature of many progressive renal diseases and is a main determinant that leads to an irreversible loss of renal function. In chronic cyclosporin A nephrotoxicity, we previously reported that inflammatory responses such as macrophage infiltration preceded interstitial fibrosis. This inflammation was accompanied by an elevation in renal nuclear factor κB (NF-κB) activity. Similar findings were obtained in chronic tacrolimus nephrotoxicity and obstructive nephropathy. Inhibition of NF-κB markedly attenuated renal inflammation and interstitial fibrosis in these models. Furthermore, administration of oral adsorbent (Kremezin ® ) significantly attenuated the increase in renal NF-κB activity and concomitantly reduced interstitial inflammation and renal fibrosis in chronic renal failure rats. Elimination of indoxyl sulfate by this adsorbent is likely involved in this mechanism since it is known that indoxyl sulfate activates NF-κB in renal tubular cells. It is suggested that strategy aiming at NF-κB inhibition is important to prevent the progression of renal fibrosis.

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Section: Renal Protective Effect Of Oral Adsorbent Ast-120 and Nf-κbmentioning

confidence: 99%

Molecular Mechanisms and Therapeutic Strategies of Chronic Renal Injury: The Role of Nuclear Factor κB Activation in the Development of Renal Fibrosis

et al. 2006

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“…Indoxyl sulfate (IS), a naturally occurring metabolite of tryptophan, is considered to be a key target uremic toxin for AST-120 (11). The toxin is thought to be involved in the progression of CRF because it is present in high levels in the serum of patients with CRF and causes tubulointerstitial injuries in rodent models (12,13).…”

Section: Introductionmentioning

confidence: 99%

An Oral Adsorbent, AST-120 Protects Against the Progression of Oxidative Stress by Reducing the Accumulation of Indoxyl Sulfate in the Systemic Circulation in Renal Failure

Shimoishi

Anraku²,

Kitamura³

et al. 2007

Pharm Res

104

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Purpose. The effect of AST-120, an oral adsorbent, on oxidative stress in the systemic circulation in chronic renal failure (CRF) was examined and the potential role of indoxyl sulfate (IS), an uremic toxin adsorbed by AST-120, in inducing the formation of reactive oxygen species (ROS) in the vascular system was studied, in vitro and in vivo. Materials and methods. The level of oxidized albumin, a marker for oxidative stress in the systemic circulation was determined by HPLC, as previously reported. The mRNA levels of TGF-b 1 and Oat1 were measured by quantitative RT-PCR. The IS induced ROS generation in cultured human umbilical vein endothelial cells (HUVECs) was estimated using a fluorescence microplate reader.Results. An increase in the ratio of oxidized to unoxidized albumin was determined using 5/6 nephrectomized rats (CRF rats) compared to a control group. The ratio was significantly reduced in the group that received AST-120 of 4 weeks, suggesting that AST-120 inhibits oxidative stress in CRF. An anti-oxidative effect of AST-120 was also observed in CRF rats with a similar renal function. The ratio of oxidized albumin was correlated with serum IS levels in vivo. The same relationship was also observed in CRF rats with the continued administration of IS. In addition, IS dramatically increased the generation of ROS in both a dose-and time-dependent manner in HUVEC, suggesting that accumulated IS may play an important role in enhancing intravascular oxidative stress. Conclusion. We propose that AST-120 reduces IS concentrations in the blood that induces ROS production in endothelial cells, thereby inhibiting the subsequent occurrence of oxidative stress in the systemic circulation in renal failure.

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“…In serum, approximately 95% of indoxyl sulfate is bound to serum albumin. AST-120 reduces the serum and urine levels of indoxyl sulfate in uremic rats and patients by adsorbing indole in the intestines, consequently stimulating its excretion into feces (23,27,28,29,30,32,34,35). The administration of indoxyl sulfate to 5/6-nephrectomized rats promoted the progression of CKD accompanied by enhanced gene expression of transforming growth factor (TGF)-β1, tissue inhibitor of metalloproteinase (TIMP)-1 and proα1(I)collagen (21,22).…”

Section: Metabolism Of Indoxyl Sulfate a Uremic Toxinmentioning

confidence: 99%

Iindoxyl Sulfate, A Tryptophan Metabolite, Induces Nephro-Vascular Toxicity

Niwa

2012

Biotechnology & Biotechnological Equipment

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Suppressed Serum and Urine Levels of Indoxyl Sulfate by Oral Sorbent in Experimental Uremic Rats

Cited by 53 publications

References 6 publications

Molecular Mechanisms and Therapeutic Strategies of Chronic Renal Injury: The Role of Nuclear Factor κB Activation in the Development of Renal Fibrosis

Molecular Mechanisms and Therapeutic Strategies of Chronic Renal Injury: The Role of Nuclear Factor κB Activation in the Development of Renal Fibrosis

An Oral Adsorbent, AST-120 Protects Against the Progression of Oxidative Stress by Reducing the Accumulation of Indoxyl Sulfate in the Systemic Circulation in Renal Failure

Iindoxyl Sulfate, A Tryptophan Metabolite, Induces Nephro-Vascular Toxicity

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