Effect of pentoxifylline on CdCl2-induced nephrotoxicity in the rat.
We developed a rat model of cadmium (Cd)-induced nephrotoxicity and tried to prevent renal damage by treating the animals with pentoxifylline (PTX). Sprague-Dawley (SD) rats given CdCl2 3.0 mg/kg sc, daily for 2 wk showed evidences of renal proximal tubular damage, including 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). PTX significantly improved the urinary excretion of NAG and %TRP. Urine volume was increased threefold in the CdCl2-treated rats and fivefold in the Cd + PTX-treated rats, respectively, as compared with saline-treated control. Total protein, AAP, and creatinine clearance, showed no change after PTX administration. Concentration of Cd in the renal cortex was three times higher than that in the renal medulla, but there were no differences in concentration between the Cd-treated rats and the Cd + PTX-treated rats. Our animal model was useful in studying the renal tubular damage produced by cadmium. PTX appears useful for improving the nephrotoxicity of Cd.
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; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D019256:Cadmium Chloride; D002712:Chlorides / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002712:Chlorides; D002104:Cadmium; D000118:Acetylglucosaminidase; D019256:Cadmium Chloride; D010431:Pentoxifylline