Cerium Oxide Nanoparticles Inhibits Oxidative Stress and Nuclear Factor-kappa B Activation in H9c2 Cardiomyocytes Exposed to Cigarette Smoke Extract

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Abstract

Cigarette smoke contains and generates a large amount of reactive oxygen species (ROS) that affect normal cellular function and have pathogenic consequences in the cardiovascular system. Increased oxidative stress and inflammation are considered to be an important mechanism of cardiovascular injury induced by cigarette smoke. Antioxidants may serve as effective therapeutic agents against smoke-related cardiovascular disease. Because of the presence of oxygen vacancies on its surface and self-regenerative cycle of its dual oxidation states, Ce(3+) and Ce(4+), cerium oxide (CeO(2)) nanoparticles offer a potential to quench ROS in biological systems. In this study, we determined the ability of CeO(2) nanoparticles to protect against cigarette smoke extract (CSE)-induced oxidative stress and inflammation in cultured rat H9c2 cardiomyocytes. CeO(2) nanoparticles pretreatment of H9c2 cells resulted in significant inhibition of CSE-induced ROS production and cell death. Pretreatment of H9c2 cells with CeO(2) nanoparticles suppressed CSE-induced phosphorylation of I kappa B alpha, nuclear translocation of p65 subunit of nuclear factor-kappa B (NF-kappa B), and NF-kappa B reporter activity in H9c2 cells. CeO(2) nanoparticles pretreatment also resulted in a significant down-regulation of NF-kappa B-regulated inflammatory genes tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, and inducible nitric-oxide synthase and further inhibited CSE-induced depletion of antioxidant enzymes, such as copper zinc superoxide dismutase, manganese superoxide dismutase, and intracellular glutathione content. These results indicate that CeO(2) nanoparticles can inhibit CSE-induced cell damage via inhibition of ROS generation, NF-kappa B activation, inflammatory gene expression, and antioxidant depletion and may have a great potential for treatment of smoking-related diseases.