Pretreatment with tadalafil attenuates cardiotoxicity induced by combretastatin A4 disodium phosphate in rats

Combretastatin A4 disodium phosphate (CA4DP) is a prodrug of combretastatin (CA4), microtubule-disassembling agent that exhibits antitumor effects by inhibiting tumor cell proliferation and inducing morphological changes apoptosis in vascular endothelial cells tumors. However, cardiotoxicity induced ischemia hypertension severe adverse event. In this study, we focused on the fact phosphodiesterase (PDE) 5 inhibitors dilate heart peripheral blood vessels aimed to investigate whether co-administration tadalafil, PDE5 inhibitor, can attenuate without altering effect CA4DP. To cardiotoxicity, CA4DP and/or tadalafil were administered rats, pressure, echocardiography, histopathology, cGMP concentration myocardium examined. Administration increased systolic decreased cardiac function, lowered levels myocardium, led necrosis myocardial cells. Co-administration attenuated these CA4DP-induced changes. effect, canine mammary carcinoma lines (CHMp-13a) human umbilical vein cultured with CA4 tube disruption CHMp-13a transplanted into nude mice treated tadalafil. CA4-induced inhibition not affected co-treatment xenograft reduced These results revealed damage was while maintaining efficacy.