Protective Effect Of Ocotillol Against Doxorubicin-induced Acute And Chronic Cardiac Injury

Objective:We want to investigate the protective effect of pseudoginsenoside ocotillol against doxorubicin (Dox)-induced cytotoxicity and its possible mechanism.Methods:1. In the acute injury model, male mice were given one dose of Dox dissolved in0.9%NaCl intraperitoneally (i.p.) at20mg/kg. The survival curve was presented and the difference was compared between co-treated group and Dox group.2. In the chronic animal model, male mice were given total6doses of Dox dissolved in0.9%NaCl i. p. at3mg/kg (accumulative dose18mg/kg) every other day. There were the control group, the Dox group, the octillol group, and the co-treated with ocotillol group. We will measure the counts of white blood cell (WBC), red blood cell (RBC) and platelet (PLT), the level of the creatine kinase (CK) and creatine kinase MB fraction (CK-MB) in plasma and the content of glutathione (GSH) and malondialdehyde (MDA) in heart tissue. The two pathologists with blind investigation and the representative pictures also presented.Results:1. In the acute injury model, co-treated with ocotillol group did prolong the survival rate (p=0.087, compared with Dox group).2. In the chronic animal model, compared with Dox group, co-treated with ocotillol group had markedly alleviated WBC counts (p<0.05), and Dox in presence or absence of ocotillol had no obvious effects on RBC and PLT counts. Compared with Dox group, co-treated group can significantly decrease the counts of CK/CK-MB (P<0.05) and the content of MDA. While, it can significantly alleviate the reduction of the GSH (P<0.05).ECG Examination shows that Dox elevated heart rates and pre-treated with different dosage of ocotillol, less histopathological changes were observed.Conclusion:These results indicated that ocotillol could attenuate cardiotoxicity induced by Dox, and its possible mechanism may be by increasing the endogenous antioxidant capacity and reducing peroxide damage.