Oral L-arginine supplementation ameliorates urinary risk factors and kinetic modulation of Tamm-Horsfall glycoprotein in experimental hyperoxaluric rats

Clin Chim Acta. 2005 Oct;360(1-2):141-50. doi: 10.1016/j.cccn.2005.04.016.

Abstract

Background: Oral supplementation of l-arginine (l-arg) is found to be beneficial in many kidney disorders. We determined whether l-arg supplementation safeguards the renal epithelial cell damage induced by hyperoxaluria with excretion of urinary marker enzymes and lithogenic salts with special reference to Tamm-Horsfall glycoprotein (THP).

Methods: Hyperoxaluria was induced by 0.75% ethylene glycol (EG) in drinking water. l-Arg was co-supplemented at the dose of 1.25 g/kg b.w. orally for 28 days. At the end of experimental period, 24-h urine samples were collected in all the experimental groups. Isolation and purification of THP was carried in rat urine and were subjected to spectrophotometric crystallization assay and calcium-(14)C-oxalate binding studies. Determination of the lithogenic risk factors like calcium, oxalate, phosphorus, citrate, and marker enzymes such as lactate dehydrogenase (LDH) and gamma-glutamyltransferase (gamma-GT) were carried out in the collected urine sample.

Results: Urinary excretion of calcium and oxalate was significantly increased in EG-treated rats. In l-arg supplemented hyperoxaluric rats, these concentrations were significantly (p<0.001) decreased when compared to that of hyperoxaluric rats, and were moderately elevated from that of control rats. The activities of urinary marker enzymes, both LDH and gamma-GT were 2-fold increased in EG-treated rats, when compared to control rats, but these values were maintained near normal in l-arg supplemented EG-treated rats. Citrate excretion was enhanced in the l-arg co-supplemented hyperoxaluric rats. In spectrophotometric crystallization assay system, l-arg supplemented rat THP showed inhibition in nucleation and aggregation phases, whereas EG-treated rat THP showed promotion of both calcium oxalate nucleation and aggregation phases. In calcium-(14)C-oxalate binding assay, THP derived from hyperoxaluric rats exhibited 2-fold increase (p<0.001) in the Ca*Ox binding when compared to control and l-arg supplemented animals.

Conclusions: l-Arg could act as a potent antilithic agent, by increasing the level of citrate in the hyperoxaluria-induced rats and decreasing calcium oxalate binding to the THP. l-Arg also effectively prevents the deposition of calcium oxalate crystals by curtailing the renal epithelial damage and protein oxidation as evidenced by the normal activities of urinary marker enzymes in l-arg supplemented hyperoxaluric rats.

MeSH terms

  • Animals
  • Arginine / administration & dosage*
  • Biomarkers / urine
  • Calcium Compounds / analysis
  • Calcium Oxalate / metabolism
  • Citric Acid / urine
  • Clinical Enzyme Tests
  • Dietary Supplements
  • Epithelial Cells / drug effects
  • Epithelial Cells / pathology
  • Ethylene Glycol
  • Hyperoxaluria / chemically induced
  • Hyperoxaluria / drug therapy*
  • Hyperoxaluria / urine*
  • Kidney / pathology
  • Male
  • Mucoproteins / isolation & purification
  • Mucoproteins / metabolism
  • Mucoproteins / urine*
  • Oxides / analysis
  • Protective Agents / administration & dosage
  • Rats
  • Rats, Wistar
  • Risk Factors
  • Uromodulin

Substances

  • Biomarkers
  • Calcium Compounds
  • Mucoproteins
  • Oxides
  • Protective Agents
  • Umod protein, rat
  • Uromodulin
  • Calcium Oxalate
  • Citric Acid
  • Arginine
  • lime
  • Ethylene Glycol