Dietary Calcium Alleviates Fluorine-Induced Liver Injury in Rats by Mitochondrial Apoptosis Pathway

Excessive fluoride (F) exposure can lead to liver damage; moreover, recent studies found that the addition of appropriate calcium (Ca) can alleviate the symptom of skeletal fluorosis. However, whether Ca can relieve F-induced liver damage through the mitochondrial apoptosis pathway has not been reported yet. Therefore, we assessed the liver morphology, serum transaminase content, liver oxidative stress-related enzymes, and apoptosis-related gene and protein expression in Sprague Dawley (SD) rats treated with 150 mg/L sodium fluoride (NaF) and different concentrations of calcium carbonate (CaCO₃) for 120 days. Our results showed that NaF brought out pathological changes in liver morphology, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels increased, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) content decreased, and malondialdehyde (MDA) content increased, suggesting that NaF caused hepatotoxicity and oxidative stress. In addition, the results of quantitative real-time PCR (qRT-PCR) and immunohistochemistry showed that NaF exposure upregulated the expression of Bcl-2-associated x protein (Bax), rho-related coiled-coil kinase 1 (ROCK1), cytochrome C (Cyto-C) mRNA and protein (P < 0.01), and downregulated B cell lymphoma 2 (Bcl-2) protein and mRNA (P < 0.01), indicating that excessive F exposure activated mitochondrial-mediated apoptosis in the liver. However, the addition of 1% CaCO₃ to the diet significantly increased the expression of anti-apoptotic gene Bcl-2 (P < 0.01), inhibited the activation of the mitochondrial apoptosis pathway, and reduced mitochondrial damage. In summary, supplementing 1% CaCO₃ in the diet can alleviate the NaF-induced liver cell damage through the mitochondrial apoptosis pathway.