ARGININE REDUCES KIDNEY COLLAGEN ACCUMULATION, CROSS-LINKING, LIPID-PEROXIDATION, GLYCOXIDATION, KIDNEY WEIGHT AND ALBUMINURIA IN THE DIABETIC KK MOUSE

In diabetic nephropathy a major current concept for pathogenesis is in creased collagen accumulation in the glomerulus by increased collagen synthesis and decreased degradation. In the present study, we tested t he hypothesis whether arginine is able to influence kidney lipid perox idation, glycoxidation, collagen accumulation, glucose-mediated cross- linking, hydroxy radical attack, protein oxidation, nitric oxide forma tion and albuminuria in the diabetic kk mouse. Ten diabetic kk mice we re given arginine 50 mg/kg body weight, 10 diabetic kk mice were not t reated and used as negative controls and 10 kk mice were kept as healt hy controls. Our results show that oral administration of low-dose arg inine reduces kidney collagen accumulation as reflected by kidney hydr oxyproline, cross-linking as reflected by pentosidine, lipid peroxidat ion, glycoxidation as reflected by carboxymethyl lysine, kidney weight and albuminuria in the diabetic Me mouse. Albuminuria in untreated an imals was closely correlated with lipid peroxidation. Our results in t he spontaneously diabetic kk mouse representing type 2 diabetes mellit us therefore confirm and extend recent findings of collagen reduction by arginine in a different animal model. The mechanism of reducing pro teinuria can be assigned to the blocking of lipid peroxidation product s by L-arginine.