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The present work-study the decreasing fluoride ions toxicity on the rat heart via loading them on the chitosan nanoparticles (Cs NPs) surface to form the biologically compatible composite (Cs@NaF). The obtained nanocomposite was characterized by different techniques such as field emission scanning electron microscopy (FEG-SEM), zeta potential, and x-ray diffraction (XRD). The biochemical parameters in the albino rats perform, where twenty-eight male adult Sprague Dawley rats (average body weight of 150 ± 10 g) were obtained from the Faculty of Agriculture, Alexandria University, then acclimatized for two weeks before the experiment and divided into four groups in galvanized wire cages at room temperature (22-25 °C) with a 12-h photoperiod and fed a well-balanced commercial diet. The blood samples were obtained from the vena cava of the rat heart via estimation of the troponin T, Lactate dehydrogenase, and creatine phosphokinase. Also, immunoglobulins (IgA, IgM, and IgG) and hematological measurements have been performed on the rat heart. To express all of the data, the mean and standard error of the mean are utilized by (ANOVA), followed by Tukey's multiple comparison test. The modified chitosan with fluoride decreases the toxicity of fluoride via improving the rat heart function due to the presence of Cs NPs helped to mitigate some of the negative effects of fluoride therapy., (Copyright © 2022 Elsevier B.V. All rights reserved.)