Effect of polyaspartic acid on CdCl2-induced nephrotoxicity in the rat.
We produced an animal model of CdCl2 nephrotoxicity in rats, and treated them with polyaspartic acid (PAA) to prevent renal damage. Male Sprague-Dawley (SD) rats (190-200 g) were used to induce proximal renal tubular damage by daily injection of CdCl2 3.0 mg/1,000 g body wt for 2 wk. CdCl2-exposed SD rats exhibited significant increases in urine volume, urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), and fractional excretion of sodium (FENa) and a decrease in the percentage of tubular reabsorption of phosphate (%TRP). Of these indicators of proximal tubular function, AAP and %TRP are more sensitive than NAG or FENa. No glycosuria or aminoaciduria, however, were observed. PAA markedly improved these indicators of proximal tubular function. Daily urinary protein excretion and creatinine clearance, on the other hand, did not change after administration of PAA. Cd concentrations in the cortex were 3 times higher than in the medulla, however, there were no differences between Cd-treated rats and PAA-treated rats. Our animal model is an excellent one for determining the effect of cadmium on renal proximal tubule damage. PAA appears to be useful in the treatment of CdCl2 nephrotoxicity.
Shibasaki
T
T
Second Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Nakano
H
H
Ohno
I
I
Ishimoto
F
F
Sakai
O
O
D000118:Acetylglucosaminidase / Q000652:urine; D000626:Aminopeptidases / Q000652:urine; D000818:Animals; D018826:CD13 Antigens; D002104:Cadmium / Q000633:toxicity*; D019256:Cadmium Chloride; D002712:Chlorides / Q000633:toxicity*; D004195:Disease Models, Animal; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine
D002712:Chlorides; D010455:Peptides; D010710:Phosphates; D002104:Cadmium; C017645:polyaspartate; D012964:Sodium; D000118:Acetylglucosaminidase; D000626:Aminopeptidases; D018826:CD13 Antigens; D019256:Cadmium Chloride