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.