Toxicity of sodium fluoride to the postnatally developing rat kidney
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Sodium fluoride (NaF) shows minimal kidney toxicity in young rats, but postweaning rats exhibit significant renal damage and impaired function after NaF exposure. Kidney sensitivity to fluoride increases sharply after weaning.
Area of Science:
- Toxicology
- Developmental Biology
- Nephrology
Background:
- The adult rat kidney is susceptible to sodium fluoride (NaF) toxicity.
- The impact of fluoride on the developing kidney remains largely unknown.
Purpose of the Study:
- To investigate renal function and potential toxicity following NaF exposure during early development (first 4 weeks) in Sprague-Dawley rats.
- To determine the age-dependent sensitivity of the rat kidney to NaF toxicity.
Main Methods:
- Rats received single intraperitoneal injections of NaF (0, 30, or 48 mg/kg) on postnatal days 1, 8, 15, or 29.
- Renal function was assessed 24, 48, and 120 hours post-exposure, including urine volume, osmolality, concentration ability, pH, and chloride content.
- Kidney histology and morphology were examined using light microscopy.
Main Results:
- Younger rats (Days 1, 8, 15) showed only minor, transient renal alterations (e.g., decreased body weight, altered urinary pH, changes in chloride excretion) at the tested NaF doses.
- Rats treated on Day 29 (postweaning) exhibited significant renal toxicity, including increased kidney weight, profound diuresis, reduced urine concentrating ability, glucosuria, and hematuria.
- Histological examination revealed lesions in the proximal tubules of Day 29 rats exposed to NaF.
Conclusions:
- The developing kidney of suckling rats is remarkably resistant to NaF-induced toxicity.
- Renal sensitivity to NaF toxicity increases abruptly after weaning, with postweaning rats showing marked susceptibility.
- These findings highlight a critical developmental window for fluoride nephrotoxicity in rats.
Abstract:
The adult rat kidney is an important target organ for sodium fluoride; however, the toxicity of fluoride to the developing kidney is unknown. This study examined renal function following NaF exposure during the first 4 weeks after birth. Sprague-Dawley rats received a single ip injection of 0, 30, or 48 mg/kg NaF on postnatal Day 1, 8, 15, or 29. Alterations in renal function, histology, and morphology were determined 24, 48, and 120 hr after exposure. Measurements of renal function included urine volume, osmolality, the ability to concentrate urine during water deprivation, urinary pH, and chloride content. Rats were then sacrificed and their kidneys processed for observation by light microscopy. Some minor alterations in renal function were observed in the three youngest age groups after NaF exposure. These changes included decreased body weight after treatment with 30 or 48 mg/kg NaF but increased kidney-body weight ratio in the 48 mg/kg group on Day 1; decreased urinary pH in both dose groups after treatment on Day 1 or 8; increased urinary volume 120 hr after treatment on Day 8; and decreased chloride excretion in the 48 mg/kg group 24 hr after injection on Day 1. None of these effects was severe. In contrast to these results, marked renal toxicity was observed in postweaning rats treated on Day 29. The NaF exposure resulted in increased kidney weight and kidney/body weight ratio, profound diuresis, decreased urinary osmolality, and decreased ability to concentrate urine during water deprivation. Urinary chloride excretion was decreased for the first 2 days after NaF exposure, then increased in water-deprived rats 120 hr after treatment. Glucosuria and hematuria were present for 2 days after treatment with 48 mg/kg. Histological lesions were apparent in the proximal tubules of the treated Day 29 rats. Thus, the kidney of the suckling rat is largely unresponsive to NaF toxicity. Renal sensitivity increases abruptly after weaning in the Day 29 rat.