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

• Published in: Diabetes research and clinical practice Vol. 34; no. 3; pp. 127 - 133
• Main Authors: Yamauchi, Akira, Takei, Izumi, Makita, Zenji, Nakamoto, Shinya, Ohashi, Norimi, Kiguchi, Hideko, Ishii, Toshiharu, Koike, Takao, Saruta, Takao
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 1997; Elsevier Science
• Subjects: Advanced glycation endproducts; Albuminuria - prevention & control; Aminoguanidine; Animals; Associated diseases and complications; Basement Membrane - drug effects; Biological and medical sciences; Blood Glucose - metabolism; Body Weight - drug effects; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Diabetic nephropathy; Disease Models, Animal; Drug Evaluation, Preclinical; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Glomerular Mesangium - drug effects; Glomerular Mesangium - ultrastructure; Glycation End Products, Advanced - blood; Guanidines - pharmacology; Medical sciences; Otsuka Long-Evans Tokushima Fatty rats; Rats; Rats, Inbred Strains; Diabetic nephropathy; Advanced glycation endproducts; Aminoguanidine; Otsuka Long-Evans Tokushima Fatty rats; Endocrinopathy; Kidney disease; Biological properties; Animal model; Urinary system disease; Rat; Diabetes mellitus; Treatment efficiency; Rodentia; Albumin; Glycosylation; Non insulin dependent diabetes; Glycation; Vertebrata; Mammalia; Nephropathy; Treatment; Animal; Inhibitor; Microalbuminuria; Proteinuria
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/S0168-8227(96)01339-3

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.