Sodium butyrate attenuates sodium fluoride-induced cardiac injury in rats via modulating oxidative stress, inflammation, and apoptosis.

As a well-recognized double-edged element in health and disease, low concentrations of fluoride are beneficial for preventing dental caries, but chronic exposure to excessive fluoride induces multi-system toxicity, including cardiotoxicity, for which no specific therapeutic agents are currently available. This study explored whether sodium butyrate (NaB), a natural derivative of short-chain fatty acids, attenuates sodium fluoride (NaF)-induced cardiac injury in rats by regulating oxidative stress, inflammation, and apoptosis. Forty-eight Sprague-Dawley rats were randomized into Control, NaB, NaF, and NaF + NaB groups. After 17 weeks of NaF exposure (NaB co-administered in the last 4 weeks), cardiac injury was assessed via histopathology, myocardial biomarkers, and molecular assays for oxidative stress, inflammation, and apoptosis. NaF exposure reduced the heart-to-brain weight ratio by 17.8%, dysregulated biomarkers (cTnI ↓19.3%, LDH ↑20.5%), induced histopathological damage, and disrupted oxidative stress (MDA ↑21.5%, SOD ↓19.2%, CAT ↓26.1%), inflammation (TNF-α ↑40.1%, IL-6 ↑27.9%, IL-10 ↓21.9%), and apoptosis (cleaved Caspase-3/pro-Caspase-3 ratio ↑51.1%, Bcl-2/Bax ratio ↓53.5%). NaB reversed these changes, restoring myocardial structure and molecular homeostasis. These findings indicate that NaB alleviates NaF-induced cardiac injury through antioxidant, anti-inflammatory, and anti-apoptotic effects, suggesting it may serve as a potential natural therapeutic agent for fluoride-associated cardiac injury.