Effects of aminoguanidine and tolrestat on the development of ocular and renal structural changes in experimental diabetic rats.
Studies that researched the role of aminoguanidine and tolestat in the prevention of diabetic retinopathy and nephropathy resulted in conflicting data. We investigated the effects of these agents in the prevention of ocular and renal changes in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intravenous injection of STZ in 30 rats. Ten rats that were not given STZ served as non-diabetic control (Group 1). Ten STZ-diabetic rats that were not given any treatment served as diabetic control (Group 2). Groups 3 and 4 were composed of STZ-induced diabetic rats (10 each) that were given tolrestat and aminoguanidine respectively. Eyes and kidneys were examined at the 24th week under electronmicroscopy. Cataract was observed in all six of the surviving rats in Groups 2 and 4, and in one of 6 surviving rats in group 3. Cataract development was lower in Group 3 than Groups 2 and 4. All retinal samples obtained from group 2 demonstrated a number of structural abnormalities, whereas there were no significant ultrastructural changes in groups 3 and 4. Groups 2 and 3 demonstrated mesangial proliferation and expansion, diffuse glomerular basement membrane (GBM) thickening, and focal GBM thickening in the bulb form. Group 4 demonstrated a normally appearing mesangial space, minimal diffuse but no focal GBM thickening. The urinary albumin excretion (UAE) was lower in Group 4 than the other groups. In conclusion, our results suggest that aminoguanidine may be an important agent for the prevention of renal changes, whereas tolrestat may be effective for the prevention of ocular changes in diabetes mellitus.
Azal
O
O
Gülhane Military School of Medicine, Department of Endocrinology, Ankara, Turkey.
Yönem
A
A
Güler
S
S
Cakir
B
B
Baydar
A
A
Corakçi
A
A
Kutlu
M
M
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002386:Cataract / Q000517:prevention & control; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D003930:Diabetic Retinopathy / Q000517:prevention & control*; D004231:Diuresis / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D006146:Guanidines; D009281:Naphthalenes; C040550:tolrestat; D000449:Aldehyde Reductase; D019001:Nitric Oxide Synthase; C004479:pimagedine