Effects of aminoguanidine on serum advanced glycation endproducts, urinary albilmin excretion, mesangial expansion, and glomerular basement membrane thickening in Otsuka Long-Evans Tokushima fatty rats.
This study evaluated the effects of treatment with an inhibitor of advanced glycation endproducts, aminoguanidine, on the development of albuminuria, mesangial expansion and glomerular basement membrane (GBM) thickening in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which we found to be an excellent model of non insulin-dependent diabetes mellitus (NIDDM), for its very close similarity to human NIDDM. OLETF rats were randomized into a non-treatment diabetic group (D-group, n = 5) and an aminoguanidine-treated group (AG-group, n = 5). The AG-group was given 100 mg/dl aminoguanidine HCl in free drinking water. Treatment was started at 16 weeks of age. We measured body weight, plasma glucose, total cholesterol, triglycerides and the urinary albumin excretion (UAE) rate before and after treatment at regular intervals. At 56 weeks of age, we measured serum advanced glycation endproducts (AGE), mesangial expansion and glomerular basement membrane. There were no significant differences in pre-treatment body weight, plasma glucose and UAE between the D-group and the AG-group. Likewise, after treatment there were no significant differences in body weight, plasma glucose, total cholesterol, triglycerides and immunoreactive insulin. Significant differences were, however, noted in serum AGE (63.2 +/- 3.5 and 51.8 +/- 3.0 U AGE/ml, P < 0.05), UAE (203.6 +/- 37.7 and 89.8 +/- 18.6 mg/day, P < 0.05), fractional mesangial volume (21.3 +/- 1.7 and 16.7 +/- 0.8%, P < 0.05) and GBM thickness (453 +/- 17 and 366 +/- 50 nm, P < 0.05) between the D-group and the AG-group. Our results suggest that aminoguanidine inhibits the AGE formation and the development of diabetic nephropathy in OLETF rats.
Yamauchi
A
A
Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Takei
I
I
Makita
Z
Z
Nakamoto
S
S
Ohashi
N
N
Kiguchi
H
H
Ishii
T
T
Koike
T
T
Saruta
T
T
D000419:Albuminuria / Q000517:prevention & control*; D000818:Animals; D001485:Basement Membrane / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000648:ultrastructure; D017127:Glycation End Products, Advanced / Q000097:blood*; D006146:Guanidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D006146:Guanidines; C004479:pimagedine