Cilostazol ameliorates nephropathy in type 1 diabetic rats involving improvement in oxidative stress and regulation of TGF-Beta and NF-kappaB.
Diabetic nephropathy is characterized as the progressive development of renal insufficiency in a setting of hyperglycemia. Previous studies indicate that reactive oxygen species (ROS) play an important role in high glucose-induced renal injury. Cilostazol was reported to lower the production of superoxide significantly in situ. We hypothesized that cilostazol administration in streptozotocin-induced diabetic rats exerts effects via improving oxidative stress. Male Sprague-Dawley rats were fed with cilostazol (5 mg/kg or 25 mg/kg) for 12 weeks after streptozotocin-induced diabetes mellitus. The results showed that cilostazol decreased reactive oxygen species activity significantly in the kidneys of diabetic rats and improved the urine albumin/creatinine ratio. Cilostazol can also improve the levels of serum cholesterol, triglyceride, and LDL-cholesterol. Additionally, diabetes-caused increased glomerular size, TGF-beta, and NF-kappaB decreased under treatment with cilostazol in diabetic rats. Our results indicate that cilostazol has beneficial effects in early diabetic nephropathy.
Lee
Wen-Chin
WC
Division of Nephrology, Department of Internal Medicine, Show Chwan Memorial Hospital, Taiwan.
Chen
Hong-Chen
HC
Wang
Chih-Ying
CY
Lin
Pei-Ying
PY
Ou
Tin-Tsz
TT
Chen
Chen-Chang
CC
Wen
Mei-Chin
MC
Wang
John
J
Lee
Huei-Jane
HJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D000077407:Cilostazol; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D001786:Blood Glucose; D016328:NF-kappa B; D012709:Serum Albumin; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D003404:Creatinine; D000077407:Cilostazol