Andrographolide protects against doxorubicin-and arsenic trioxide-induced toxicity in cardiomyocytes.

ABSTRACT

BACKGROUND: Andrographolide (AG) is a lactone diterpene with valuable biological activities. This in vitro study evaluated whether AG can protect cardiomyocytes under toxicities triggered with anti-cancer chemotherapeutic agents, doxorubicin (DOX) and arsenic trioxide (ATO). METHODS AND RESULTS: H9C2 cells were pretreated with AG (0.5-10 µM) for 24 h and then exposed to DOX (1 µM) or ATO (35 µM) for another 24 h period. For determination of cell viability or cytotoxicity, MTT and lactate dehydrogenase (LDH) assay were used. Total oxidant and antioxidant capacities were estimated by determining hydroperoxides and ferric reducing antioxidant power (FRAP) levels. Real time-polymerase chain reaction was also used for quantitative evaluation of TLR4 gene expression. AG inhibited cardiomyocytes proliferation at the concentrations of more than 20 µM. However, it considerably enhanced cell viability and decreased cytotoxicity of DOX and ATO at the concentration range of 2.5-10 µM in MTT and LDH assays. AG significantly declined hydroperoxides concentration in ATO-treated cardiomyocytes and raised FRAP value in DOX- and ATO-treated cells. Furthermore, AG notably lessened TLR4 expression in H9C2 cells after exposure to DOX- and ATO. CONCLUSION: In conclusion, these data presented that AG was able to reverse DOX- and ATO-induced cardiotoxicity in vitro. The cardiomyocyte protective activities of AG may be due to the decrease in TLR4 expression and total oxidant capacity and increase in total antioxidant capacity.