Usefulness of the assessment of urinary enzyme leakage in monitoring acute fluoride nephrotoxicity.
A single oral dose of sodium fluoride (NaF) in aqueous solution was given to male Wistar rats. Twenty-four-hour urine samples were collected and examined to evaluate fluoride-induced acute renal damage. The following parameters were measured in 24-h urine: urine volume and urinary excretion of fluoride, N-acetyl-beta-d-glucosaminidase (NAG), alpha-glutathione-S-transferase (alpha-GST), and creatinine (CR). Fluoride exposure produced specific, dose-dependent changes of these parameters. Significant increases of fluoride and fluoride-induced polyuria were observed. NAG as specific marker of proximal convoluted tubule (PCT) function showed a significant increase when the lowest dose of fluoride was administered. At this minimal dose, alpha-GST, a specific marker for the S3 segment, did not show a significant increase but presented the strongest relationship (r = 0. 83) to fluoride dose. No significant changes were measured for CR excretion, which showed a low correlation coefficient (r = 0.36) to administered fluoride. The specific differences in the increase pattern of these parameters show that the PCT is more susceptible to damage by low-dose fluoride than the S3 segment or the glomerulus. We concluded that both NAG and alpha-GST are useful for the diagnosis of fluoride-induced acute nephrotoxicity. Proper evaluation of these urinary indices may be of help to establish the site and extent of kidney injury in acute fluoride toxicity.
Usuda
K
K
World Health Organization Organization Mondiale De La Santé Batiment L-216 CH-1211 Genéve 27, Suisse.
Kono
K
K
Dote
T
T
Nishiura
H
H
Tagawa
T
T
D000118:Acetylglucosaminidase / Q000652:urine*; D000818:Animals; D002138:Calibration; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005460:Fluorides, Topical / Q000633:toxicity*; D005982:Glutathione Transferase / Q000652:urine*; D007668:Kidney / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000652:urine*; D007928:Lethal Dose 50; D016014:Linear Models; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012969:Sodium Fluoride / Q000633:toxicity*
D005460:Fluorides, Topical; D012969:Sodium Fluoride; D003404:Creatinine; D005982:Glutathione Transferase; D000118:Acetylglucosaminidase