Fasudil Attenuates Adriamycin-Induced Cardiac Damage by Modifying Oxidative Stress and Apoptosis Mediated Cellular Signaling [post]

Yi Yan, Chengyu Xiang, Dingguo Zhang
2021 unpublished
PURPOSETo explore the protective mechanism of fasudil,a Rho kinase inhibitor, on acute cardiac injury induced by adriamycin(ADR).METHODSIn vitro investigations on H9C2 cell line, as well as an in vivo study in a mouse model of ADR-induced acute cardiomyopathy, were performed. In vitro, H9C2 cells were treated with fasudil for 30mins then incubated with ADR for 24 hours. Cells were collected for immunohistochemistry and western blot study, respectively. In vivo, C57BL6 mice were randomly divided
more » ... into the following four groups: ①ADR group;②low-dose fasudil ( ADR+L);③high-dose fasudil ( ADR+H); and ④control group(CON). Animals were injected i.p 20 mg/kg ADR once in group①~③. And animals were injected i.p fasudil (2 or 10 mg/kg/day ) daily once for six times in group ②and ③,respectively. Blood samples and heart tissues were collected for assays.RESULTSIn vitro, fasudil treatment ameliorated ADR-induced immunofluorescence reaction of 8-OHdG, decreased the expression of TUNEL cells and protein of Bax、Caspase-3 and p53,and increased the expression of protein of Bcl-2 and SIRT 1. In the mouse model, administration of fasudil significantly ameliorated ADR-induced cardiac damage, suppressed cell apoptosis and senescence, ameliorated redox imbalance and DNA damage.CONCLUSIONFasudil has the protective effect on adriamycin induced acute cardiotoxicity, which partially attributed to its antioxidant, anti-senescence, and anti-apoptotic effects of inhibiting the RhoA/Rho kinase signaling pathway.
doi:10.21203/rs.3.rs-323927/v1 fatcat:r2dgpwcp7vbqxhxze4g3lcnrsu