Effects of an oral adsorbent on oxidative stress and fibronectin expression in experimental diabetic nephropathy

Sun Ha Lee, Bo Young Nam, Ea Wha Kang, SeungHyeok Han, Jin Ji Li, Do Hee Kim, Seung Hye Kim, Seung Jae Kwak, Jung Tak Park, Tae Ik Chang, TaeHyun Yoo, Dae Suk Han, Shin-Wook Kang

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Abstract

Background. Previous studies have demonstrated that AST-120 (Kremezin ®), a well-known oral adsorbent, inhibits the progression of diabetic (DM) and non-DM chronic kidney disease along with a decrease in oxidative stress. This study was undertaken to investigate whether AST-120 could reduce oxidative stress and ameliorate the development of nephropathy in experimental DM rats with normal renal function.Methods. Rats were injected with diluent (C, n = 16) or 65 mg/kg streptozotocin intraperitoneally (DM, n = 16), and eight rats from each group were treated with chow containing 5% AST-120. After 3 months, plasma advanced oxidation protein products (AOPP) and total malondialdehyde (MDA) levels, 24-h urinary albumin excretion, and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) excretion were determined by ELISA. Glomerular endothelial nitric oxide synthase (eNOS), subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (gp91phox, p47phox and p22phox), and fibronectin (FN) mRNA and protein expressions were determined by real-time PCR and western blot, respectively. In addition, dichlorodihydrofluorescein diacetate (DCF-DA) staining was performed to detect glomerular reactive oxygen species (ROS) production.Results. Compared to the C group, 24-h urinary albumin excretion was significantly higher in the DM group (P < 0.01), and AST-120 treatment significantly reduced albuminuria in DM rats (P < 0.05). Glomerular eNOS, gp91phox, p47phox and FN expression were significantly increased in DM rats compared to C rats, and these increases in DM glomeruli were significantly abrogated by AST-120 treatment (P < 0.05). The increases in plasma AOPP and MDA levels as well as renal oxidative stress in DM rats, assessed by DCF-DA staining and urinary 8-OHdG excretion rates, were also significantly attenuated by AST-120 treatment (P < 0.05).Conclusion. In conclusion, the renoprotective effects of AST-120 in DM nephropathy seem to be associated with the amelioration of enhanced oxidative stress and FN expression under diabetic conditions.

Original languageEnglish
Pages (from-to)2134-2141
Number of pages8
JournalNephrology Dialysis Transplantation
Volume25
Issue number7
DOIs
Publication statusPublished - 2010 Jan 1

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Diabetic Nephropathies
Fibronectins
Oxidative Stress
Advanced Oxidation Protein Products
Nitric Oxide Synthase Type III
Malondialdehyde
Albumins
Staining and Labeling
Kidney
Albuminuria
AST 120
Streptozocin
Chronic Renal Insufficiency
NADP
Real-Time Polymerase Chain Reaction
Reactive Oxygen Species
Oxidoreductases
Therapeutics
Western Blotting
Enzyme-Linked Immunosorbent Assay

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

Cite this

Lee, Sun Ha ; Nam, Bo Young ; Kang, Ea Wha ; Han, SeungHyeok ; Li, Jin Ji ; Kim, Do Hee ; Kim, Seung Hye ; Kwak, Seung Jae ; Park, Jung Tak ; Chang, Tae Ik ; Yoo, TaeHyun ; Han, Dae Suk ; Kang, Shin-Wook. / Effects of an oral adsorbent on oxidative stress and fibronectin expression in experimental diabetic nephropathy. In: Nephrology Dialysis Transplantation. 2010 ; Vol. 25, No. 7. pp. 2134-2141.
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title = "Effects of an oral adsorbent on oxidative stress and fibronectin expression in experimental diabetic nephropathy",
abstract = "Background. Previous studies have demonstrated that AST-120 (Kremezin {\circledR}), a well-known oral adsorbent, inhibits the progression of diabetic (DM) and non-DM chronic kidney disease along with a decrease in oxidative stress. This study was undertaken to investigate whether AST-120 could reduce oxidative stress and ameliorate the development of nephropathy in experimental DM rats with normal renal function.Methods. Rats were injected with diluent (C, n = 16) or 65 mg/kg streptozotocin intraperitoneally (DM, n = 16), and eight rats from each group were treated with chow containing 5{\%} AST-120. After 3 months, plasma advanced oxidation protein products (AOPP) and total malondialdehyde (MDA) levels, 24-h urinary albumin excretion, and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) excretion were determined by ELISA. Glomerular endothelial nitric oxide synthase (eNOS), subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (gp91phox, p47phox and p22phox), and fibronectin (FN) mRNA and protein expressions were determined by real-time PCR and western blot, respectively. In addition, dichlorodihydrofluorescein diacetate (DCF-DA) staining was performed to detect glomerular reactive oxygen species (ROS) production.Results. Compared to the C group, 24-h urinary albumin excretion was significantly higher in the DM group (P < 0.01), and AST-120 treatment significantly reduced albuminuria in DM rats (P < 0.05). Glomerular eNOS, gp91phox, p47phox and FN expression were significantly increased in DM rats compared to C rats, and these increases in DM glomeruli were significantly abrogated by AST-120 treatment (P < 0.05). The increases in plasma AOPP and MDA levels as well as renal oxidative stress in DM rats, assessed by DCF-DA staining and urinary 8-OHdG excretion rates, were also significantly attenuated by AST-120 treatment (P < 0.05).Conclusion. In conclusion, the renoprotective effects of AST-120 in DM nephropathy seem to be associated with the amelioration of enhanced oxidative stress and FN expression under diabetic conditions.",
author = "Lee, {Sun Ha} and Nam, {Bo Young} and Kang, {Ea Wha} and SeungHyeok Han and Li, {Jin Ji} and Kim, {Do Hee} and Kim, {Seung Hye} and Kwak, {Seung Jae} and Park, {Jung Tak} and Chang, {Tae Ik} and TaeHyun Yoo and Han, {Dae Suk} and Shin-Wook Kang",
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Effects of an oral adsorbent on oxidative stress and fibronectin expression in experimental diabetic nephropathy. / Lee, Sun Ha; Nam, Bo Young; Kang, Ea Wha; Han, SeungHyeok; Li, Jin Ji; Kim, Do Hee; Kim, Seung Hye; Kwak, Seung Jae; Park, Jung Tak; Chang, Tae Ik; Yoo, TaeHyun; Han, Dae Suk; Kang, Shin-Wook.

In: Nephrology Dialysis Transplantation, Vol. 25, No. 7, 01.01.2010, p. 2134-2141.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Effects of an oral adsorbent on oxidative stress and fibronectin expression in experimental diabetic nephropathy

AU - Lee, Sun Ha

AU - Nam, Bo Young

AU - Kang, Ea Wha

AU - Han, SeungHyeok

AU - Li, Jin Ji

AU - Kim, Do Hee

AU - Kim, Seung Hye

AU - Kwak, Seung Jae

AU - Park, Jung Tak

AU - Chang, Tae Ik

AU - Yoo, TaeHyun

AU - Han, Dae Suk

AU - Kang, Shin-Wook

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Background. Previous studies have demonstrated that AST-120 (Kremezin ®), a well-known oral adsorbent, inhibits the progression of diabetic (DM) and non-DM chronic kidney disease along with a decrease in oxidative stress. This study was undertaken to investigate whether AST-120 could reduce oxidative stress and ameliorate the development of nephropathy in experimental DM rats with normal renal function.Methods. Rats were injected with diluent (C, n = 16) or 65 mg/kg streptozotocin intraperitoneally (DM, n = 16), and eight rats from each group were treated with chow containing 5% AST-120. After 3 months, plasma advanced oxidation protein products (AOPP) and total malondialdehyde (MDA) levels, 24-h urinary albumin excretion, and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) excretion were determined by ELISA. Glomerular endothelial nitric oxide synthase (eNOS), subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (gp91phox, p47phox and p22phox), and fibronectin (FN) mRNA and protein expressions were determined by real-time PCR and western blot, respectively. In addition, dichlorodihydrofluorescein diacetate (DCF-DA) staining was performed to detect glomerular reactive oxygen species (ROS) production.Results. Compared to the C group, 24-h urinary albumin excretion was significantly higher in the DM group (P < 0.01), and AST-120 treatment significantly reduced albuminuria in DM rats (P < 0.05). Glomerular eNOS, gp91phox, p47phox and FN expression were significantly increased in DM rats compared to C rats, and these increases in DM glomeruli were significantly abrogated by AST-120 treatment (P < 0.05). The increases in plasma AOPP and MDA levels as well as renal oxidative stress in DM rats, assessed by DCF-DA staining and urinary 8-OHdG excretion rates, were also significantly attenuated by AST-120 treatment (P < 0.05).Conclusion. In conclusion, the renoprotective effects of AST-120 in DM nephropathy seem to be associated with the amelioration of enhanced oxidative stress and FN expression under diabetic conditions.

AB - Background. Previous studies have demonstrated that AST-120 (Kremezin ®), a well-known oral adsorbent, inhibits the progression of diabetic (DM) and non-DM chronic kidney disease along with a decrease in oxidative stress. This study was undertaken to investigate whether AST-120 could reduce oxidative stress and ameliorate the development of nephropathy in experimental DM rats with normal renal function.Methods. Rats were injected with diluent (C, n = 16) or 65 mg/kg streptozotocin intraperitoneally (DM, n = 16), and eight rats from each group were treated with chow containing 5% AST-120. After 3 months, plasma advanced oxidation protein products (AOPP) and total malondialdehyde (MDA) levels, 24-h urinary albumin excretion, and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) excretion were determined by ELISA. Glomerular endothelial nitric oxide synthase (eNOS), subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (gp91phox, p47phox and p22phox), and fibronectin (FN) mRNA and protein expressions were determined by real-time PCR and western blot, respectively. In addition, dichlorodihydrofluorescein diacetate (DCF-DA) staining was performed to detect glomerular reactive oxygen species (ROS) production.Results. Compared to the C group, 24-h urinary albumin excretion was significantly higher in the DM group (P < 0.01), and AST-120 treatment significantly reduced albuminuria in DM rats (P < 0.05). Glomerular eNOS, gp91phox, p47phox and FN expression were significantly increased in DM rats compared to C rats, and these increases in DM glomeruli were significantly abrogated by AST-120 treatment (P < 0.05). The increases in plasma AOPP and MDA levels as well as renal oxidative stress in DM rats, assessed by DCF-DA staining and urinary 8-OHdG excretion rates, were also significantly attenuated by AST-120 treatment (P < 0.05).Conclusion. In conclusion, the renoprotective effects of AST-120 in DM nephropathy seem to be associated with the amelioration of enhanced oxidative stress and FN expression under diabetic conditions.

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U2 - 10.1093/ndt/gfq063

DO - 10.1093/ndt/gfq063

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VL - 25

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JF - Nephrology Dialysis Transplantation

SN - 0931-0509

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