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

Sun Ha Lee, Bo Young Nam, Ea Wha Kang, Seung Hyeok Han, Jin Ji Li, Do Hee Kim, Seung Hye Kim, Seung Jae Kwak, Jung Tak Park, Tae Ik Chang, Tae Hyun 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 Jul

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

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    Lee, S. H., Nam, B. Y., Kang, E. W., Han, S. H., Li, J. J., Kim, D. H., Kim, S. H., Kwak, S. J., Park, J. T., Chang, T. I., Yoo, T. H., Han, D. S., & Kang, S. W. (2010). Effects of an oral adsorbent on oxidative stress and fibronectin expression in experimental diabetic nephropathy. Nephrology Dialysis Transplantation, 25(7), 2134-2141. https://doi.org/10.1093/ndt/gfq063