Oral L-arginine supplementation ameliorates urinary risk factors and kinetic modulation of Tamm-Horsfall glycoprotein in experimental hyperoxaluric rats.
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.
Department of Medical Biochemistry, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai-600 113, India.
Viswanathan
V
Pragasam
Periandavan
P
Kalaiselvi
Kamalanathan
K
Sumitra
Shanmugarajan
S
Srinivasan
Palaninathan
P
Varalakshmi
D000818:Animals; D001120:Arginine / Q000008:administration & dosage*; D015415:Biomarkers / Q000652:urine; D017610:Calcium Compounds / Q000032:analysis; D002129:Calcium Oxalate / Q000378:metabolism; D019343:Citric Acid / Q000652:urine; D004796:Clinical Enzyme Tests; D019587:Dietary Supplements; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D019855:Ethylene Glycol; D006959:Hyperoxaluria / Q000139:chemically induced / Q000188:drug therapy* / Q000652:urine*; D007668:Kidney / Q000473:pathology; D008297:Male; D009088:Mucoproteins / Q000302:isolation & purification / Q000378:metabolism / Q000652:urine*; D010087:Oxides / Q000032:analysis; D020011:Protective Agents / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D058949:Uromodulin
D015415:Biomarkers; D017610:Calcium Compounds; D009088:Mucoproteins; D010087:Oxides; D020011:Protective Agents; C548614:Umod protein, rat; D058949:Uromodulin; D002129:Calcium Oxalate; D019343:Citric Acid; D001120:Arginine; C016538:lime; D019855:Ethylene Glycol