Aucubin relieving doxorubicin-induced myocardial damage through Nrf2-mediated oxidative stress

Yang Jingjing; Ke Haixia; Zhang Haizhu; Li Lufei

doi:10.3969/j.issn.1674-4055.2024.02.10

Abstract：Objective To study the protective effect and relative molecular mechanism of Aucubin(AU)on myocardial damage induced by doxorubicin(DOX)in mice.Methods Male ICR mice(n=40)were randomly divided into control group,DOX group,DOX+AU group and DOX+AU+ML385 group.The model of myocardial damage was established by intraperitoneal injection of DOX,then was intragastrically given AU for treatment and intraperitoneal injection of ML385 for inhibiting Nrf2 activation in mice.After treatment for 4 weeks,body weight,cardiac mass,cardiac index(CI),serum myocardial enzymes,serum oxidative stress indexes,myocardial pathological changes and expressions of key proteins in pathway of nuclear factor erythropoietin 2 related factor 2(Nrf2)/heme oxygenase 1(HO-1)were compared among 4 groups.Results The comparison in above-mentioned indexes had significant statistical differences among 4 groups(P<0.05).The body weight,cardiac mass,CI,superoxide dismutase(SOD)and glutathione(GSH)were significantly lower(P<0.05),and lactic dehydrogenase(LDH),creatine kinase(CK),aspertate aminotransferase(AST),malondialdehyde(MDA)and expressions of Nrf2,Keap1 and HO-1 were significantly higher(P<0.05)in DOX group than those in control group.The body weight,cardiac mass,CI,SOD,GSH and expressions of Nrf2,Keap1 and HO-1 were significantly higher(P<0.05),and LDH,CK,AST and MDA were significantly lower(P<0.05)in DOX+AU group than those in DOX group.The body weight,cardiac mass,CI,SOD,GSH and expressions of Nrf2,Keap1 and HO-1 were significantly lower(P<0.05),and LDH,CK,AST and MDA were significantly higher(P<0.05)in DOX+AU+ML385 group than those in DOX+AU group.Conclusion AU has a protective effect of myocardial damage induced by DOX in mice,and the mechanism may be related to than AU can activate Nrf2/HO-1 pathway and reduce oxidative stress damage.