Terminalia arjuna Bark Nanosuspension Attenuates Fluoride-Induced Cardiotoxicity in Rats by Modulating Oxidative Stress, Inflammation and ACE Expression.

Fluoride exposure through drinking water is an independent risk factor for cardiovascular disease. Terminalia arjuna is well known for its cardioprotective properties, including positive inotropic effects, hypolipidemic activity and coronary vasodilation. This study aimed to evaluate the effect of T. arjuna bark nanosuspension on fluoride-induced cardiotoxicity in rats. The nanosuspension was prepared using polysorbate-80 as an aqueous stabilizer and exhibited uniform particles with a mean size of 118.0 nm. Forty rats were divided into five groups: Group I served as the control, while the other four groups were exposed to sodium fluoride (100 ppm) daily through drinking water for 28 days. Group III received 200 mg/kg T. arjuna bark extract, while Groups IV and V were administered T. arjuna bark nanosuspension at doses of 100 mg/kg and 50 mg/kg, respectively. Fluoride administration caused significant increases in blood pressure and serum biochemical markers, along with decreased cardiac antioxidant defenses, in rats compared with the control group. Fluoride exposure also increased angiotensin-converting enzyme (ACE), nuclear factor kappa B (NF-κB), and tumor necrosis factor alpha (TNF-α) levels, as well as altered the histology and immunohistochemical expression (Bcl-2 and caspase-9) of cardiac tissue. Treatment with T. arjuna bark nanosuspension significantly attenuated these fluoride-mediated cardiotoxic effects and preserved the normal histological architecture of the cardiac tissue. However, the magnitude of these effects indicates that T. arjuna bark nanosuspension at a dose of 100 mg/kg has greater ameliorative potential.