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


CONCLUSIONS
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.
Lee
Sun Ha
SH
Yonsei University College of Medicine, Department of Internal Medicine, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul, South Korea.
Nam
Bo Young
BY
Kang
Ea Wha
EW
Han
Seung Hyeok
SH
Li
Jin Ji
JJ
Kim
Do Hee
DH
Kim
Seung Hye
SH
Kwak
Seung-Jae
SJ
Park
Jung Tak
JT
Chang
Tae Ik
TI
Yoo
Tae-Hyun
TH
Han
Dae Suk
DS
Kang
Shin-Wook
SW
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D000419:Albuminuria / Q000378:metabolism; D000818:Animals; D002244:Carbon / Q000008:administration & dosage / Q000494:pharmacology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005353:Fibronectins / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010087:Oxides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013311:Streptozocin
D005353:Fibronectins; D010087:Oxides; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D013311:Streptozocin; D002244:Carbon; D000080242:8-Hydroxy-2'-Deoxyguanosine; C040896:AST 120; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D003849:Deoxyguanosine