Histopathological changes of renal tissue following sodium fluoride administration in two consecutive generations of mice. Correlation with the urinary elimination of fluoride.

The present study was designed to investigate the toxic effects (evaluated as histopathological changes) of sodium fluoride on the kidney in two consecutive generations of NMRI mice. An attempt to correlate the toxicity with the urinary elimination of fluoride has been made, as urinary fluoride excretion has been widely used as an indicator of fluoride intake and exposure. Six mixed (males and females) animal groups have been constituted by dividing the populations of mice derived from pregnant females (named "mothers" 0.5 mg sodium fluoride) treated with 0.5 mg sodium fluoride by daily gavage and pregnant females (named "mothers" 0.25 mg sodium fluoride) treated with 0.25 mg sodium fluoride by daily gavage; three types of sodium fluoride treatments were administrated: homeopathic, allopathic-homeopathic and allopathic. When the animals reached the adulthood, by randomization, they were selected in pairs for giving birth to the second generation of mice. No treatments were administrated to the second generation of mice; thus, the urinary elimination of fluoride in the second generation is attributed to exposure at sodium fluoride before birth. The administration of sodium fluoride to the first generation (F1) is realized until the mice reached the adulthood. For the first generation, the urine was collected at three times, every three weeks: at the age of four weeks, seven weeks and 11 weeks; single sampling urine, at the age of four weeks, has been conducted for the second generation. The urine samples have been analyzed using the ion selective electrode method for fluoride. For the histopathological examination, the animals were killed by cervical dislocation; the kidneys were collected in a 10% formalin solution. The preparation of samples for optical microscopy was realized with Hematoxylin-Eosin staining. The results indicate that the elimination of fluoride was similar (at the second evaluation, at 7-week-old of the first generation) for the both generations of mice. Histopathological observation of the kidney has revealed granular dystrophy of the renal tubules, necrosis of the endothelial cells and of the mesangial cells of renal glomerulus. The study indicates that different sodium fluoride treatments produce some pathological aspects of the kidneys and influence the urinary elimination of fluoride in two consecutive generations of mice. For the higher doses, the pathological changes of the kidney are more important, and the urinary elimination of fluoride is higher, especially for the allopathic doses.