Amelioration of diabetic nephropathy in OLETF rats by prostaglandin I(2) analog, beraprost sodium.
BACKGROUND
Strict control of blood glucose and blood pressure levels sometimes fails to delay the development of diabetic nephropathy, and an effective therapy is not yet available. The present study aimed to examine whether the prostaglandin I(2) analog beraprost sodium (BPS) ameliorates diabetic nephropathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rat.


METHODS
Fifty-week-old OLETF rats were divided into three groups according to treatment; 400 microg/kg body weight (BW) BPS, 200 microg/kg BW BPS, and 0.9% saline administration. Kidney histology, index of glomerulosclerosis, and glomerular volume were determined, and urine and serum chemistry were assessed.


RESULTS
The values for urine protein excretion and serum blood urea nitrogen in BPS-treated rats were significantly lower than those in untreated rats. In rats treated with 400 microg/kg BW BPS, neither sclerotic changes nor inflammatory cell infiltration were observed. Index of glomerulosclerosis and glomerular volume were also significantly reduced compared with untreated rats. Intriguingly, BPS reduced the level of serum triglyceride. In the glomerulus of treated rats, advanced glycation end product formation and macrophage influx were suppressed in a dose-dependent manner.


CONCLUSIONS
These findings indicate that BPS has a therapeutic effect on diabetic nephropathy in the OLETF rat, which suggests a potential application of this drug in the treatment of human diabetic nephropathy.
Watanabe
Maho
M
Division of Nephrology and Rheumatology, Department of Internal Medicine, Faculty of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.
Nakashima
Hitoshi
H
Mochizuki
Shizue
S
Abe
Yasuhiro
Y
Ishimura
Atsunori
A
Ito
Kenji
K
Fukushima
Takao
T
Miyake
Katsuhisa
K
Ogahara
Satoru
S
Saito
Takao
T
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000627:therapeutic use; D007150:Immunohistochemistry / Q000379:methods; D007668:Kidney / Q000187:drug effects; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000187:drug effects; D008297:Male; D051381:Rats; D020334:Rats, Inbred OLETF; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
D008055:Lipids; D014665:Vasodilator Agents; C048081:beraprost; D011464:Epoprostenol