Recurrent exposure to ferric oxide nanoparticles alters myocardial oxidative stress, apoptosis and necrotic markers in male mice

- Ferric oxide nanoparticles induces oxidative stress in mice myocardial tissue.
- Induced oxidative stress damages the biomolecules.
- Recurrent exposure to Ferric oxide nanoparticles triggers necrosis and apoptosis and alters cardiac functional markers.

The cardiotoxicity of iron oxide nanoparticles (Fe2O3-NPs) in mice was investigated. The mice were intraperitoneally administered with Fe2O3-NPs at the dose of 25 and 50 mg/kg bw for 30 days at seven days interval. In vivo MRI analysis reveals the Fe2O3-NPs accumulation in the cardiac system. Also, serum iron estimation and Prussian blue staining confirms the iron deposition in circulatory system. Cardiac dysfunction was assessed by ECG analysis and further validated by evaluating the functional markers such as cardiac Troponin-1 (cTnI) expression, AChE activity and levels of LDH and CK-MB in cardiac tissue. Fe2O3-NPs exposure disturbs the balance between the oxidants and antioxidants resulting in oxidative myocardial damages. In consequence, damaged mitochondria, diminished ATP level and NOX4 over expression were observed in the intoxicated groups indicating the role of Fe2O3-NPs in oxidative stress. A dose dependant increase in oxidative stress mediates apoptosis through upregulation of Bax, cytochrome c and cleaved caspase 3 in the 25 mg/kg treated group. Sustained oxidative stress suggest the occurrence of necrosis in addition to apoptosis in 50 mg/kg treated group evidenced by altered expression pattern of cleaved PARP, cytochrome c, Bax and cleaved caspase 3. In addition, triphenyl tetrazolium chloride (TTC) staining confirms cardiac necrosis in 50 mg/kg Fe2O3-NPs treated group.