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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 
 Nephrology Dialysis Transplantation, Vol.25(7) : 2134-2141, 2010 
Journal Title
 Nephrology Dialysis Transplantation 
Issue Date
BACKGROUND: Previous studies have demonstrated that AST-120 (Kremezin((R))), 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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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
강신욱(Kang, Shin Wook) ORCID logo https://orcid.org/0000-0002-5677-4756
곽승재(Kwak, Seung Jae)
김도희(Kim, Do Hee)
김승혜(Kim, Seung Hye)
남보영(Nam, Bo Young)
박정탁(Park, Jung Tak) ORCID logo https://orcid.org/0000-0002-2325-8982
유태현(Yoo, Tae Hyun) ORCID logo https://orcid.org/0000-0002-9183-4507
이금희(Li, Jin Ji)
이순하(Lee, Sun Ha)
장태익(Chang, Tae Ik)
한대석(Han, Dae Suk)
한승혁(Han, Seung Hyeok) ORCID logo https://orcid.org/0000-0001-7923-5635
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