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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 
Journal Title
Issue Date
Administration, Oral ; Albuminuria/metabolism ; Animals ; Carbon/administration & dosage ; Carbon/pharmacology* ; Deoxyguanosine/analogs & derivatives ; Deoxyguanosine/metabolism ; Diabetic Nephropathies/metabolism* ; Diabetic Nephropathies/physiopathology ; Disease Models, Animal ; Disease Progression* ; Fibronectins/metabolism* ; Male ; Malondialdehyde/metabolism ; NADPH Oxidases/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Oxidative Stress/drug effects* ; Oxidative Stress/physiology ; Oxides/administration & dosage ; Oxides/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Streptozocin
AST-120 ; diabetic nephropathy ; fibronectin ; oxidative stress
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. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Shin Wook(강신욱) ORCID logo https://orcid.org/0000-0002-5677-4756
Kwak, Seung Jae(곽승재)
Kim, Do Hee(김도희)
Kim, Seung Hye(김승혜)
Nam, Bo Young(남보영)
Park, Jung Tak(박정탁) ORCID logo https://orcid.org/0000-0002-2325-8982
Yoo, Tae Hyun(유태현) ORCID logo https://orcid.org/0000-0002-9183-4507
Li, Jin Ji(이금희)
Lee, Sun Ha(이순하)
Chang, Tae Ik(장태익)
Han, Dae Suk(한대석)
Han, Seung Hyeok(한승혁) ORCID logo https://orcid.org/0000-0001-7923-5635
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