Protective Effect of Fisetin on Subacute and Chronic Arsenic and Fluoride Co-Exposure Induced Hepatic, Renal and Cardiac Toxicities in Mice

Abstract

Arsenic and fluoride are potent toxicants frequently present in drinking water and food, posing severe health risks through toxic impacts on key organs, primarily by inducing oxidative stress. Combined exposure to these elements exacerbates oxidative damage, yet effective strategies for preventing and managing their toxicities remain elusive. Fisetin, a bioflavonoid known for its antioxidant and anti-inflammatory properties, has demonstrated protective effects in multiple toxicity studies. However, its effect on arsenic- and fluoride-induced toxicity in vital organs (particularly the liver, kidneys, and heart) remains unexplored. This study investigates the protective potential of fisetin against subacute and chronic co-exposure to arsenic and fluoride-induced organ toxicity in a murine model. Male mice were administered arsenic and fluoride through drinking water, while fisetin (5, 10, and 20 mg/kg/day, orally) was co-administered simultaneously. Animals were sacrificed at 4 weeks (subacute) and 24 weeks (chronic) for liver, kidney, and heart tissue analysis, assessing biochemical markers and arsenic accumulation. Spectrophotometry study revealed some degree of arsenic chelation with fisetin. The results of In Vivo studies showed that both subacute and chronic exposure led to significant increases in pro-oxidant levels (ROS, TBARS, and nitrite) and arsenic accumulation, along with reduced GSH content in these organs compared to control. Fisetin treatment dose-dependently reduced oxidative stress and arsenic content in vital organs of exposed animals. The findings highlight fisetin's antioxidant activity and its capacity to reduce arsenic burden as potential protective mechanisms. These results support fisetin or fisetin-rich fruit consumption as a therapeutic strategy to mitigate organ toxicity from arsenic and fluoride co-exposure.