Insights into the causal role of diesel exhaust particles in ventricular arrhythmogenesis : protective effects of antioxidant cerium oxide nanoparticles

Epidemiological studies suggest an association between air pollution and ventricular arrhythmias, with reactive oxygen species (ROS) playing a crucial role. However, the causal relationship and long-term effects remain uncertain, and the effectiveness of interventions aimed at reducing ROS requires further investigation. Here we aimed to evaluate the effects of a 3-weeks exposure to diesel exhaust particles (DEPs) on ventricular arrhythmogenesis, explore the underlying mechanisms, and assess the potential of cerium oxide nanoparticles (CeONP) as a ROS-detoxifying intervention. Sprague-Dawley rats underwent intratracheal instillation of saline without or with DEPs (7.5 g/Kg for 1-3 weeks). Ventricular arrhythmia inducibility was then assessed in isolated hearts using a protocol of programmed electrical stimulation. Cardiac hypertrophy, collagen content, inflammation and oxidative stress were analyzed using histology, Western blot, RT-qPCR, and measurement of malondialdehyde content. The potential protective effects of CeONP (0.5 mg/Kg/week, i.p.) were also tested. DEP exposure for 3 weeks increased the incidence and duration of sustained ventricular tachyarrhythmias (VTs), a finding that correlated with a moderate increase in interstitial collagen (from 3.11 ± 0.12% in controls to 4.80 ± 0.21% in DEP-exposed rats, p. < 0.001), and an early upregulation in the expression of collagen and other fibrotic and inflammatory markers. These effects associated with prolonged QRS complex and enhanced malondialdehyde content (356.7 ± 21.2 vs. 455.3 ± 17.2 μmol/g tissue, p = 0.0066) after 3 weeks. CeO2NP treatment reduced oxidative stress and myocardial fibrosis, reversed electrocardiographic changes and attenuated DEP-induced pro-arrhythmic effects. Conclusions: DEP exposure increases the incidence and duration of sustained VTs, collagen deposition and oxidative stress in rats. Treatment with CeO2NP attenuate these effects, arising as a potential novel strategy to mitigate the deleterious effects of air pollution.