Dilazep hydrochloride, an antiplatelet drug, prevents progression of diabetic nephropathy in Otsuka Long-Evans Tokushima fatty rats.
Diabetic nephropathy is a leading cause of end-stage renal disease in industrialized countries. Although the mechanisms for the development and progression of diabetic nephropathy are not fully understood, platelet activation may participate in its pathogenesis by promoting microthrombus formation. In this study, we investigated the effects of dilazep hydrochloride, an antiplatelet agent, on the development and progression of diabetic nephropathy in Otsuka Long-Evans Tokushima fatty (OLETF) rats, a type 2 diabetes mellitus animal model. Administration of dilazep hydrochloride significantly reduced the increase of urinary protein excretions and N-acetyl-beta-D-glucosaminidase (NAG) activity in OLETF rats. Furthermore, dilazep hydrochloride treatment prevented glomerulosclerosis and tubular atrophy and reduced positive staining for type IV collagen in the glomeruli of diabetic rats. These results indicate that platelet activation plays a dominant role in the development and progression of diabetic nephropathy. Our study suggests that dilazep hydrochloride is a valuable new drug for the treatment of diabetic patients with nephropathy.
Yamagishi
S
S
Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. shoichi@med.kurume-u.ac.jp
Koga
K
K
Inagaki
Y
Y
Amano
S
S
Okamoto
T
T
Takeuchi
M
M
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D004109:Dilazep / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D020334:Rats, Inbred OLETF
D010975:Platelet Aggregation Inhibitors; D000118:Acetylglucosaminidase; D004109:Dilazep