In the present study, we tested the hypothesis whether agmatine and sp
ermidine, metabolites of arginine metabolism, share the pharmacologica
l activities of arginine reducing collagen accumulation in the diabeti
c kidney. Eleven db/db mice were administered agmatine and 12 db/db mi
ce spermidine (50 mg/kg body weight), Ten db/db mice received no treat
ment as negative controls and 10 db/db mice were treated with aminogua
nidine (50 mg/kg body weight) as positive controls. Mean kidney OH-pro
line content reflecting kidney collagen content and mean CML concentra
tion were significantly higher but acid solubility of collagen signifi
cantly lower in the untreated group than in the treated groups. Agmati
ne, although missing the alpha-amino group and the carboxyl group, and
spermidine, although missing the guanidino group, thus still revealed
the arginine activity. We hypothesize that the strongly nucleophilic
structure of polyamines common to all active compounds is able to bloc
k reactive carbonyls.