Baicalin reduces sunitinib-induced cardiotoxicity in renal carcinoma PDX model by inhibiting myocardial injury, apoptosis and fibrosis.

Sunitinib (SU), a multi-targeted tyrosine kinase inhibitor, has anticancer function but its clinical use is often limited by cardiovascular complications. Baicalin (BA) has demonstrated various pharmacological activities including antioxidant, anti-inflammatory and antiviral properties, but its potential roles in SU-induced cardiotoxicity have not been reported. In this study, we aimed to investigate the effect of BA in SU-induced cardiotoxicity by using renal carcinoma patient-derived xenograft (PDX) model. Female Nod Scid mice with renal carcinoma PDX were treated with vehicle, SU (50 mg/kg/d), BA (100 mg/kg/d), or BA combined with SU for 6 weeks. The tumor volume and weight of tumor-bearing mice were measured, and cardiovascular functions were evaluated by testing the Heart index and blood biochemical indicators, and by hematoxylin and eosin (H&E), Masson and Tunel staining. The results showed that SU therapy and combination therapy effectively inhibited the growth of renal tumors. Combination therapy inhibited SU-induced increase of creatine kinase (CK) and lactate dehydrogenase (LDH), and ameliorated the heart parameters. Moreover, BA effectively protected SU-induced cardiac dysfunction by decreasing injury, apoptosis, and fibrosis. Collectively, our results demonstrate that BA can be as a potential cardioprotective approach for cardiovascular complications during SU regimen.