Icariin exhibits protective effects on cisplatin-induced cardiotoxicity via ROS-mediated oxidative stress injury in vivo and in vitro.

ABSTRACT

BACKGROUND: Cisplatin-induced cardiotoxicity severely limits its clinical application as an antitumor drug and increases the risk of cardiovascular disease. Icariin (ICA), the main flavonoid isolated from Epimedii Folium, has been demonstrated to have various beneficial effects on cardiovascular disease. However, the protective effect of ICA against cisplatin-induced cardiotoxicity remains unclear. PURPOSE: In present study, we explored the protective action of ICA against cisplatin-induced cardiotoxicity and its possible molecular mechanisms in vitro and in vivo. METHODS: Mice were intraperitoneally injected with cisplatin 4 mg/kg every other day for 7 times to establish myocardial injury model. ICA (15, 30 mg/kg) was administered to mice by gavage for 21 days. H9c2 cells were treated with ICA (3, 6, 12 µM) in the presence or absence of cisplatin (40 µM), and then cell viability, oxidative stress, apoptosis, and mitochondrial function were evaluated. RESULTS: Biochemical index detection and histopathological staining analysis showed that ICA had a good protective effect on cisplatin-induced cardiotoxicity. Cellular experiments showed that ICA inhibited cisplatin-induced oxidative stress in a dose-dependent manner by regulating the levels of glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA). ICA could inhibit the expression of NF-κB and the secretion of inflammatory factors, thereby alleviating the inflammatory injury caused by cisplatin. In addition, ICA could alleviate cisplatin-induced myocardial injury by activating SIRT1 and PI3K/Akt signaling pathways and inhibiting MAPKs signaling pathway. CONCLUSION: These results suggest that ICA could attenuate cisplatin-induced cardiac injury by inhibiting oxidative stress, inflammation and apoptosis, laying a foundation for ICA to reduce chemotherapy-induced cardiotoxicity in clinical practice.