Ozone protects from myocardial ischemia-reperfusion injury via inhibition of the NLRP3 inflammasome

Ischemic heart disease (IHD) is a leading cause of morbidity and mortality worldwide. Myocardial ischemia/reperfusion injury (MIRI) is the primary cause of myocardial injury triggered by post-myocardial infarction reperfusion therapy. Its pathogenesis involves Ca²⁺ overload, the production of large amounts of oxygen-free radicals, inflammation, and cell necrosis. Growing evidence suggests that the NLRP3 inflammasome significantly contributes to the sterile inflammatory response and pyroptosis in MIRI, linking damage sensing to the initiation and amplification of the inflammatory response. Reportedly, ozone exerts anti-inflammatory and anti-infection effects by activating the antioxidant system. Additional evidence suggests that ozone inhibits NLRP3 inflammasome expression to relieve ischemic injury. In this study, we aimed to explore whether pretreating the myocardium with ozone protects it from MIRI by inhibiting the NLRP3 inflammasome. Rats were subjected to rectal infusion of ozone for 5 consecutive days, followed by ligation of the left anterior descending coronary artery for 30 min and reperfusion for 120 min to induce MIRI. Experimental results were obtained using echocardiography, triphenyltetrazolium chloride and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assay. The results showed that ozone significantly improved the diastolic function of the heart, reduced the area of myocardial infarction, and decreased the expression levels of NLRP3, pro-caspase-1, ASC, and the secretion of caspase-1, interleukin (IL)-1β, and IL-18. In summary, these findings reveal that ozone pretreatment can alleviate the damage that occurs during MIRI by inhibiting the NLRP3 Inflammasome.