title: L-arginine reduces kidney collagen accumulation and N-epsilon-(carboxymethyl)lysine in the aging NMRI-mouse.
abstract: BACKGROUND
  The aging process leads to glomerular basement membrane (GBM) thickening due to increased collagen accumulation. This mechanism can be explained by the nonenzymatic glycosylation hypothesis of collagen aging. We have published the positive effect of L-arginine on glucose-mediated cross-linking, and if the nonenzymatic glycosylation hypothesis of aging holds, the pharmacological effect of L-arginine on glucose-mediated cross-links in the aging Hannover NMRI mouse can be expected.
  
  
  METHODS
  Animals were given L-arginine 50 mg/kg body weight/day orally and compared to a control group without treatment.
  
  
  RESULTS
  Electron microscopical measurement of the GBM thickness showed significant differences between controls (4920 +/- 1680 A) and the experimental group (2345 +/- 815 A). Determination of the total kidney collagen content based upon 4-trans hydroxyproline revealed 13.9 +/- 3.9 mg/100 mg kidney weight (kw) in the untreated group versus 7.9 +/- 4.2 mg/100 mg kw in the treated group. For solubility studies based upon hydroxyproline determination, collagen was eluted by pepsin digestion. This revealed 18.7 +/- 3.9 mg/100 mg kw in the controls versus 7.8 +/- 4.8 mg/100 mg kw in the treated group. HPLC analysis of N-epsilon-(carboxymethyl)lysine (CML) showed in the treated group (1.847 +/- 0.247 nM/microM hydroxyproline) significantly lower concentrations than in the untreated group (3.399 +/- 0.349 nM/microM hydroxyproline). On sodium dodecyl sulfate (SDS) polyacrylamidegel electrophoresis, the eluates of the treated animals showed less high molecular weight material than their untreated mates.
  
  
  CONCLUSIONS
  We cannot discriminate between the probable mechanisms of cross-linking but we clearly can state that L-arginine reduces cross-linking and collagen accumulation in aging collagen type IV accompanied and strongly associated with decreased CML content.
authors.affiliation: Institute of Micromorphology and Electron Microscopy, University of Vienna.
authors.forename: W
authors.initials: W
authors.lastname: Radner
authors.forename: H
authors.initials: H
authors.lastname: Höger
authors.forename: B
authors.initials: B
authors.lastname: Lubec
authors.forename: H
authors.initials: H
authors.lastname: Salzer
authors.forename: G
authors.initials: G
authors.lastname: Lubec
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001485:Basement Membrane / Q000648:ultrastructure; D003094:Collagen / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006031:Glycosylation; D006909:Hydroxyproline / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000648:ultrastructure; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D051379:Mice
chemical_list: C048496:N(6)-carboxymethyllysine; D003094:Collagen; D001120:Arginine; D008239:Lysine; D006909:Hydroxyproline