Abstract

Acute fluoride (F) exposure adversely impairs cardiac functions. We previously reported that acute F toxicity causes modulation in oxidant and antioxidant systems, heat shock proteins, cytoskeletal proteins and AMPK signaling proteins in the myocardium of rats. With these findings, we hypothesized that acute F intoxication may trigger an acute myocardial inflammatory response through the activation of NF-kB signaling and reduction of redox signaling regulatory system. To test this hypothesis, we treated male Wistar rats with single oral doses of 45 and 90 mg/kg of F for 24 h. The myocardium of F treated rats showed increased expression of pNF-k/B , pIkKa/B eventually leading to the increased expression of downstream target TNFa-a major proinflammatory cytokine secreted in the inflammatory process. F intoxication decreased the mRNA expression of redox genes-Sirt1, Sirt3, Prdx2, Glrx1, Trx1, and Trx2. In addition, we observed decreased protein expression of Nrf2, GCLC, and NQO1 in the cardiac tissues of F treated rats. This study reveals that F toxicity triggers myocardial inflammatory response and depletes redox signaling molecules in the myocardium of rats. We conclude that NF-kB activation with decreased redox gene expression might be associated with the pathophysiology of F induced cardiac dysfunction in rats. This finding provides new insights into the cardiovascular pathophysiology in acute F toxicity.