L-ARGININE REDUCES KIDNEY LIPID-PEROXIDATION, GLYCOXIDATION AND COLLAGEN ACCUMULATION IN THE AGING NMRI MOUSE

Collagen accumulation in organs is a main feature of the physiological aging process. There are two main theories for the responsible mechan isms, the free oxygen radical and the glycoxidation theory. Both lead to carbonyle-induced protein modification, increased collagen cross-li nking and subsequently to the collagen accumulation. In previous studi es we provided evidence for the blocking of reactive carbonyles by L-a rginine in the diabetic state and present here data for this effect in the aging NMRI mouse. NMRI mice were fed L-arginine in tap water for a period of 6 months and compared to an untreated control group. Kidne y collagen content of the treated group was significantly reduced(trea ted: 8.83+/-0.72 mg collagen/100 mg kidney weight; untreated: 11.95+/- 0.98 mg collagen (100 mg kidney weight; p < 0.05). Using a colorimetri c assay for lipid peroxidation products we found significantly reduced lipid peroxidation-derived aldehydes in the treated group (treated: 0 .25+/-0.03 extinction; untreated: 0.36+/-0.04 extinction; p<0.05). The parameter for glycoxidation, N-epsilon-carboxymethyllysine (CML) was significantly lower in the experimental group as well(treated: 2.3+/-0 .5 nM CML/mu M hydroxyproline; untreated: 4.3+/-0.52 nM CML/mu M hydro xyproline; p<0.05). No differences were observed for the biomarker of hydroxyradical attack, o-tyrosine. L-Arginine could have reduced colla gen accumulation by blocking collagen glyc(oxidation) which is known t o lead to increased collagen cross-linking, solubility and degradation as a strong correlation between both CML and collagen content (r(2) = 0.654, p<0.05) as well as between lipid peroxidation products and col lagen content (r(2) = 0.539, p<0.05) was observed.