EFFECTS OF AMINOGUANIDINE ON SERUM ADVANCED GLYCATION ENDPRODUCTS, URINARY ALBUMIN 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 adv anced glycation endproducts, aminoguanidine, on the development of alb uminuria, mesangial expansion and glomerular basement membrane (GEM) t hickening in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which we found to be an excellent model of non insulin-dependent diabetes melli tus (NIDDM), for its very close similarity to human NIDDM. OLETF rats were randomized into a non-treatment diabetic group (D-group, n = 5) a nd 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 glucos e, total cholesterol, triglycerides and the urinary albumin excretion (UAE) rate before and after treatment at regular intervals. At 56 week s of age, we measured serum advanced glycation endproducts (AGE), mesa ngial expansion and glomerular basement membrane. There were no signif icant 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 di fferences 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 GEM thickness (453 +/- 17 and 366 +/- 50 nm, P < 0.0 5) between the D-group and the AG-group. Our results suggest that amin oguanidine inhibits the AGE formation and the development of diabetic nephropathy in OLETF rats. (C) 1997 Elsevier Science Ireland Ltd.