An excess of sodium fluoride (135 mg F/kg body weight) was given in a single oral dose to male Wistar rats. Effects were investigated of fluoride-induced acute kidney intoxication on the time-dependent variations of urine volume. Also, of urinary fluoride ion (F-), alpha-glutathione-S-transferase (alpha-GST), N-acetyl-beta-D-glucosaminidase (NAG), and creatinine (CR) concentrations. Fluoride administration strongly affects these urinary biochemical indices. Of the several biomarkers studied, alpha-GST is particularly useful as marker of S3 proximal tubule damage. We found that alpha-GST shows the strongest and more durable changes as a result of the large dose of F- given to the experimental animals. Our results suggest that the toxic effect of F- on the kidney may be more pronounced in the proximal tubule than the glomeruli region, and that the disorder of the proximal tubule is more serious in the S3 segment than S1 or S2 segment. Alpha-GST proved to be a useful marker for the early detection and long-term observation of proximal renal tubular injury resulting from F- intoxication. The animal model should help to establish guidelines for the treatment of industrial workers suffering from acute renal failure resulting from accidental exposure to fluoride.
Fluoride (F) complexes are used in some fields of industry and medicine. F excretion mainly depends on kidney function. Urinary F concentration is measured to monitor the health of workers exposed to F. The toxicokinetics of F were studied by analyzing plasma concentration of F after intravenous injection of 2.86, 5.71 and 8.57 mg/kg into male Wistar rats. A dose-response relationship was recognized between these F doses and renal tissue injury. Blood samples were removed at 0, 10, 20, and 30 min, and after 1, 2, 3, 4, 5, and 6 h after injection. Plasma concentration-vs-time profiles were evaluated by a nonlinear least-squares method for fitting data to polyexponential equations and calculation of relevant pharmacokinetic parameters. Results indicated that a two-compartment model could describe the elimination of F from plasma. The beta rate constant, total plasma clearance (C1) and first-order rate constants (K21, Kel) decreased, and the half-time of the beta-phase (t1/2beta) was significantly prolonged with increasing dose. The kidney is the main target organ for F toxicity. Acute exposure to high doses of F damages renal tissue and causes renal dysfunction. The C1 of F is mainly dependent on renal F excretion. Since severe kidney damage markedly affected the toxicokinetics of F and decreased its elimination, other nephrotoxic indicators and measurement of plasma F concentration are necessary for monitoring high-dose F exposure.
(CdN) is commonly used in Ni-Cd battery factories. The possibility of accidental exposure to CdN is great. CdN is very soluble in water compared to other Cd compounds. Therefore, acute toxicity would be expected to be quick due to rapid absorption after exposure. However, the mechanisms of CdN toxicity have not been fully elucidated. We investigated the acute lethal toxicity and harmful systemic effects of acute exposure to large doses of CdN. The lethal dose and dose-response study of the liver and kidney were determined after intravenous administration of CdN in rats. The LD 50 of CdN was determined to be 5.5 mg/ kg. Doses of 2.1, 4.2, 6.3 mg/kg were selected for the dose-response study. Liver injury was induced at doses greater than 4.2 mg/kg. Severe hepatic injury occurred in the 6.3 mg/kg group, which would have been caused by acute exposure to the high concentration of Cd that exceeded the critical concentration in hepatic tissue. A remarkable decrease in urine volume in the 6.3 mg/ kg group indicated acute renal failure. A decrease in creatinine clearance suggested acute glomerular dysfunction at doses greater than 4.2 mg/kg. Increases in urinary N-acetyl-β-D-glucosaminidase/creatinine, β 2 -microglobulin and glucose in the 6.3 mg/kg group indicated proximal tubular injury. Secretion of K ion was also severely affected by proximal tubular injury and severe decreases in urine volume, and an increase in serum K ion was identified at doses greater than 4.2 mg/kg. Thus severe hyperkalemia might be associated with the cardiac-derived lethal toxicity of CdN. (J Occup Health 2007; 49: 17-24)
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