TY - JOUR
T1 - Effects of NADPH oxidase inhibitor on diabetic nephropathy in OLETF rats
T2 - The role of reducing oxidative stress in its protective property
AU - Nam, Soo Min
AU - Lee, Mi Young
AU - Koh, Jang Hyun
AU - Park, Jun Ho
AU - Shin, Jang Yel
AU - Shin, Young Goo
AU - Koh, Sang Baek
AU - Lee, Eun Young
AU - Chung, Choon Hee
PY - 2009/2/1
Y1 - 2009/2/1
N2 - Diabetic nephropathy is the most serious complication in diabetes mellitus. Oxidative stress via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and vascular endothelial growth factor (VEGF) pathway play critical roles in the development of diabetic nephropathy. We evaluated the effects of apocynin, NADPH oxidase inhibitor on diabetic nephropathy in a type 2 diabetic rat model. Sixteen Otsuka Long Evans Tokushima Fatty (OLETF) rats and 9 Long Evans Tokushima Otsuka (LETO) were divided into the following three groups: LETO rats (n = 9), control OLETF rats (n = 7) and apocynin-treated OLETF rats (n = 9). We examined body weights, plasma glucose levels, urinary albumin-creatinine ratio (ACR) and protein-creatinine ratio (PCR). At 50 weeks, experimental rats were sacrificed and their kidneys were extracted for hematoxylin eosin stain, immunohistochemical VEGF stain and VEGF mRNA real-time RT-PCR. To examine oxidative stress, we checked 24 h urinary 8-OHdG (8-hydroxy-2′-deoxyguanosine) and MDA (malondialdehyde). Urinary protein and albumin excretions were reduced after apocynin treatment, though apocynin could not significantly decrease serum glucose levels. There were improvements of glomerular and mesangial expansion in the apocynin-treated OLETF rats. Apocynin significantly decreased optical density of glomerular VEGF expression in immunohistochemical stain and reduced the concentration of 24 h urinary 8-OHdG and MDA. From these results, it was suggested that apocynin may have the potential to protect against diabetic nephropathy via amelioration of oxidative stress.
AB - Diabetic nephropathy is the most serious complication in diabetes mellitus. Oxidative stress via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and vascular endothelial growth factor (VEGF) pathway play critical roles in the development of diabetic nephropathy. We evaluated the effects of apocynin, NADPH oxidase inhibitor on diabetic nephropathy in a type 2 diabetic rat model. Sixteen Otsuka Long Evans Tokushima Fatty (OLETF) rats and 9 Long Evans Tokushima Otsuka (LETO) were divided into the following three groups: LETO rats (n = 9), control OLETF rats (n = 7) and apocynin-treated OLETF rats (n = 9). We examined body weights, plasma glucose levels, urinary albumin-creatinine ratio (ACR) and protein-creatinine ratio (PCR). At 50 weeks, experimental rats were sacrificed and their kidneys were extracted for hematoxylin eosin stain, immunohistochemical VEGF stain and VEGF mRNA real-time RT-PCR. To examine oxidative stress, we checked 24 h urinary 8-OHdG (8-hydroxy-2′-deoxyguanosine) and MDA (malondialdehyde). Urinary protein and albumin excretions were reduced after apocynin treatment, though apocynin could not significantly decrease serum glucose levels. There were improvements of glomerular and mesangial expansion in the apocynin-treated OLETF rats. Apocynin significantly decreased optical density of glomerular VEGF expression in immunohistochemical stain and reduced the concentration of 24 h urinary 8-OHdG and MDA. From these results, it was suggested that apocynin may have the potential to protect against diabetic nephropathy via amelioration of oxidative stress.
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U2 - 10.1016/j.diabres.2008.10.007
DO - 10.1016/j.diabres.2008.10.007
M3 - Article
C2 - 19111363
AN - SCOPUS:58249119832
VL - 83
SP - 176
EP - 182
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
SN - 0168-8227
IS - 2
ER -