In
diabetic nephropathy a major current concept for pathogenesis is increased
collagen accumulation in the glomerulus by increased
collagen synthesis and decreased degradation. In the present study, we tested the hypothesis whether
arginine is able to influence kidney lipid peroxidation, glycoxidation,
collagen accumulation,
glucose-mediated cross-linking, hydroxy radical attack,
protein oxidation,
nitric oxide formation and
albuminuria in the diabetic kk mouse. Ten diabetic kk mice were given
arginine 50 mg/kg
body weight, 10 diabetic kk mice were not treated and used as negative controls and 10 kk mice were kept as healthy controls. Our results show that
oral administration of low-dose
arginine reduces kidney
collagen accumulation as reflected by kidney
hydroxyproline, cross-linking as reflected by
pentosidine, lipid peroxidation, glycoxidation as reflected by
carboxymethyl lysine, kidney weight and
albuminuria in the diabetic kk mouse.
Albuminuria in untreated animals was closely correlated with lipid peroxidation. Our results in the spontaneously diabetic kk mouse representing
type 2 diabetes mellitus therefore confirm and extend recent findings of
collagen reduction by
arginine in a different animal model. The mechanism of reducing
proteinuria can be assigned to the blocking of lipid peroxidation products by
L-arginine.