Spiraeoside prevents copper oxide nanoparticles-induced myocardial impairments via regulating Wnt/β-catenin, oxidative stress, and inflammation: An echocardiographic and histopathological investigation.

Copper oxide nanoparticles (CuONPs) are widely employed in industrial and biomedical applications; however, their long-term exposure induces severe cardiac impairments. Spiraeoside (SPD) is a naturally occurring flavonoid with diverse biological properties. The current study was designed to investigate the cardioprotective effects of SPD against CuONPs-induced cardiotoxicity. Thirty-two rats were randomly allocated into four groups: control, CuONPs (100 mg/ kg), CuONPs (100 mg/kg) + SPD (200 mg/ kg), and SPD (200 mg/kg) alone treated group. Our findings showed that CuONPs exposure substantially reduced the expression of ATP2A2, RYR2, CACNA1C, and GSK3B while upregulating CAMK2D, AXIN2, WNT3A, and CTNNB1. Moreover, CuONPs intoxication induced severe oxidative imbalance as evidenced by high levels of ROS and MDA while reducing the activities of GST, GSR, CAT, HO-1, SOD and GPx. Besides, CuONPs administration increased the levels of Troponin-I, LDH, Troponin-T, CRP, BNP, NT-proBNP, CPK, and CK-MB. Severe echocardiographic alterations were found after CuONPs exposure as indicated by significant reduction in heart rate, high EDV and ESV, as well as ventricular dilation. Similarly, CuONPs induced marked upregulation of pro-inflammatory markers including COX-2, IL-6, IL-1β and TNF-α. A significant upregulation of Bax, Caspase-3, and Caspase-9 while a marked reduction in the levels of Bcl-2 was found following the exposure of CuONPs. Histopathological analysis showed severe structural myocardial damage in response to CuONPs intoxication. Nonetheless, SPD notably protected cardiac tissues via regulating calcium-dependent signaling pathways, inflammatory and apoptotic responses, echocardiographic parameters, oxidative stress, and histopathological alterations. Collectively, these findings suggest that SPD is a promising natural bioactive molecule against cardiac injury caused by nanoparticles. All preclinical studies, such as pharmacokinetic, toxicological, and dose optimization investigation, are still needed to assess the potential clinical applicability.