Protective effects of silver nanoparticles in isoproterenol-induced myocardial infarction in rats

Background: Silver nanoparticles (AgNPs) are widely used in the medical field, including cardiovascular. However, limited research has investigated the effect of AgNPs on the protection of myocardial infarction (MI). Objectives: Isoproterenol (Iso)-induced MI and the cardiac protection offered by AgNPs were investigated in the present study. Additionally, we characterized the profile of Ag in the form of nanoparticles. Methods: Twenty-four male Wistar rats were randomly divided into four groups as follows: normal, Iso, Iso + AgNO₃, and Iso + AgNP groups. AgNPs and silver ion (AgNO₃) were administered intraperitoneally at 2.5 mg/kg BW for 14 days. Iso induction was performed using two doses of 85 mg/kg BW given subcutaneously on days 13 and 14. Blood and cardiac tissue samples were taken 24 h after the last dose of Iso and checked for Creatine Kinase-MB (CK-MB), lactate dehydrogenase in plasma along with oxidative stress parameters, mitochondria biogenesis markers, and inflammation representative genes in cardiac tissue. Additionally, we analyzed the histopathological features in cardiac tissue. Results: The silver was confirmed in the form of nanoparticles by its size at intervals of 8.72–37.84 nm. Both AgNO₃ and AgNPs showed similar cardioprotective effects, as shown by the decrease in biochemical markers of cardiac toxicity, namely, CK-MB. Additionally, AgNPs group have better efficacy compared with AgNO₃ group in ameliorating Iso-mediated oxidative stress production, as evidenced by the significant decrease in malondialdehyde level and increased superoxide dismutase activity (P < 0.0001 and P < 0.01, respectively) in cardiac tissue compared with the Iso group. Mechanistically, AgNPs, but not AgNO₃, enhanced the expression levels of mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator 1-alpha in post-MI heart and reduced the protein expression of nuclear factor-kappa B (NF-κB) assessed by western blot analysis. Furthermore, these results were confirmed with the histopathological evaluation of cardiac tissue. Nevertheless, pretreatment with either AgNO₃ or AgNPs improved the aspartate aminotransferase level. Conclusion: These results suggested that AgNPs have more superior cardioprotective effect compared with AgNO₃ against Iso-induced MI, at least in part through amelioration of NF-κB expression level induced by oxidative stress overproduction.