Oridonin reduces cisplatin-induced cardiac damage: targeting oxidative stress and inflammation in chemotherapy

Cisplatin is a potent chemotherapeutic agent widely used in cancer treatment, known for its efficacy but limited by significant cardiotoxic side effects. Oridonin, a bioactive diterpenoid derived from <i>Rabdosia rubescens</i>, has demonstrated potential to mitigate these adverse effects, though this protective capability against cisplatin-induced cardiotoxicity has not been extensively explored. In this study, mice were administered oridonin orally at doses of 25 or 50 mg/kg/day for seven days. Additionally, they received cisplatin injections at a dosage of 5 mg/kg on days 3 and 6, intraperitoneally. On the eighth day, after anesthesia with sodium pentobarbital (50 mg/kg, i.p.), blood and heart samples were collected for biochemical and molecular analysis. Oridonin significantly mitigated CP-induced cardiac damage, as evidenced by reduced levels of cardiac troponin I (cTnI), creatine kinase (CK), and lactate dehydrogenase (LDH). It also decreased oxidative stress markers such as malondialdehyde (MDA), while enhancing the activity of antioxidants like superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Additionally, oridonin reduced levels of pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), and modulated apoptosis-related proteins by increasing Bcl-2 and decreasing Bax and caspase-3. The protective effects of oridonin were further linked to modulation of the p62/Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, as evidenced by increased protein levels of p62 and Nrf2, and decreased protein Keap1. Oridonin confers significant protection against the cardiac side effects of cisplatin chemotherapy, highlighting its potential as a supplementary therapy in oncological treatments.