Modulation of doxorubicin-induced cardiotoxicity by averrhoa bilimbi extract

Abstract

Introduction: Severe cardiotoxicity limits the use of doxorubicin in cancer treatment. Doxorubicin toxicity involves the generation of reactive oxygen species (ROS) and hence several antioxidants and plant products have been tried to minimise the cardiotoxicity. The Averrhoa bilimbi fruits (Family: oxalidaceae) extract had good in vitro free radical scavenging activity in preliminary tests, further, it is to screened for its protective activity against doxorubicin induced cardiotoxicity. Methods: Methanolic extract of A. bilimbi (BM) was tested for cardioprotective activity in cell lines and in BALB/c mice. BM-extract was tested on Vero-cells and H9c2(2-1)-cardiomyoblasts for its protection from doxorubicin induced toxicities. Extract-BM was examined in doxorubicin-induced acute cardiotoxicity in BALB/c mice. The cardioprotective efficacy was tested in Swiss mice with Ehrlich Ascites Carcinoma (EAC). Results: BM-extract significantly protected the doxorubicin toxicities on Vero-cells and H9c2(2-1)-cardiomyoblasts. The extract-BM pretreatment controlled doxorubicin induced toxicities in terms of reduced serum CK-MB, LDH, cardiac tissue-TBARS and elevation of other enzymatic and nonenzymatic antioxidants. Extract-BM protected the body-weight loss and DNA-fragmentation in heart tissue. Further, cardioprotection was established by histopathological examination. The combination of doxorubicin with BM-extract significantly increased the mean survival time (MST) in EAC-mice. BM-extract treatment modulated the antioxidants both in heart and liver tissues of EAC-mice. For mechanistic approach, BM-extract showed in vitro antioxidant activity (measured by DPPH and FRAP assay) and inhibited intracellular generation of ROS and nitrite in RAW264.7 cells. Conclusion: The protection from doxorubicin-induced cardiotoxicity by BM-extract was attributed to its antioxidant activity and inhibition of intracellular free radical generation.