The effect of an aldose reductase inhibitor (Epalrestat) on diabetic nephropathy in rats.
In order to clarify the possible contribution of the abnormal polyol pathway to the development of diabetic nephropathy, the effect of aldose reductase inhibitor on renal function and morphology was examined in streptozotocin (STZ)-induced diabetic rats. Six months after STZ injection, glomerular filtration rate and renal plasma flow showed marked decline with significant increase in nuclear-free mesangial area (MA) and relative mesangial area (RMA; MA per glomerular area) in diabetic rats. Oral administration of an aldose reductase inhibitor, Epalrestat, prevented renal hypofunction and mesangial expansion in diabetic rats without influencing the levels of blood glucose. These results suggest that the abnormal polyol pathway in diabetic rats is closely related to the development of mesangial expansion, a morphologic representative of diabetic glomerulopathy, and renal hypofunction.
Fukui Institute for Safety Research, Ono Pharmaceutical Co. Ltd., Japan.
I
I
Itagaki
K
K
Shimizu
Y
Y
Kamanaka
K
K
Ebata
R
R
Kikkawa
M
M
Haneda
Y
Y
Shigeta
D000419:Albuminuria; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053778:Thiazolidines
D001786:Blood Glucose; D053778:Thiazolidines; C038131:epalrestat; D012236:Rhodanine; D000449:Aldehyde Reductase