Effects of NADPH oxidase inhibitor on diabetic nephropathy in OLETF rats: the role of reducing oxidative stress in its protective property.
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 24h 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 24h 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.
Nam
Soo Min
SM
Department of Internal Medicine, Sun General Hospital, Daejeon, Republic of Korea.
Lee
Mi Young
MY
Koh
Jang Hyun
JH
Park
Jun Ho
JH
Shin
Jang Yel
JY
Shin
Young Goo
YG
Koh
Sang Baek
SB
Lee
Eun Young
EY
Chung
Choon Hee
CH
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D019610:Cytoprotection / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000652:urine; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000652:urine; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D020334:Rats, Inbred OLETF; D020318:Rats, Long-Evans; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D000098:Acetophenones; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; C056165:acetovanillone; D019255:NADPH Oxidases; D003849:Deoxyguanosine