Excessive fluoride induces renal cell apoptosis and subsequent renal dysfunction

This study investigated the mechanisms of renal injury and dysfunction induced by chronic excessive fluoride exposure. Sixty female Sprague-Dawley rats were administered sodium fluoride (NaF) at 0, 50, 100, or 150 mg/L in drinking water for 2, 4, or 6 months. NaF exposure was confirmed by elevated urinary fluoride levels. Renal function was assessed by the increase in serum creatinine, and structural damage was evaluated by histopathology. The expression of key apoptosis-related markers (Bax, Bcl-2, Caspase-3) was analyzed using qRT-PCR, immunohistochemistry, and Western blotting. Fluoride exposure caused a dose- and time-dependent increase in serum creatinine, indicating impaired glomerular filtration. Histopathological analysis confirmed significant tubular degeneration. Notably, functional impairment occurred despite no pathological change in kidney yet, suggesting that functional deficits preceded overt morphological alterations. Mechanistically, fluoride exposure induced a clear pro-apoptotic molecular shift with increased Bax and decreased Bcl-2 expression, culminating in the activation of Caspase-3. The histopathological findings were consistent with a mixed pattern of cell death. However, the integrated molecular evidence demonstrated that the activation of the intrinsic (mitochondrial) apoptotic pathway was a key mechanism contributing to the excessive fluoride-induced nephrotoxicity. In summary, a central molecular pathway involved in fluoride-induced renal injury was demonstrated, providing a foundation for assessing excessive fluoride toxicological impact.