A study on the attenuation of ATO cardiotoxicity by SOG though Nrf2/ARE pathway

Arsenic trioxide (ATO, Trisenox) is an ancient Chinese medicine which have good clinical effects for acute promyelocytic leukemia (APL). However, ATO has serious cardiotoxicity which has restricted its widely applied in clinic. Saposhnikovia divaricata (Trucz.) Schischk was an antidote to ATO in Chinese medical book. Sec-O-Glucosylhamaudol (SOG) is one of its four main active ingredients. So we explore if SOG can detoxify the ATO’s cardiotoxicity through the Nuclear factor erythroid 2-related factor 2(Nrf2) signal pathway and apoptosis pathway. We added 10 μM ATO and 10, 50, 100 μM SOG in Rat cardiac myocyte-like H9c2 cells. The results indicate SOG can active Nrf2 signal pathway, improve Nrf2 phosphorylation levels, promote the expression of Nrf2, HO-1, NQO1 gene and protein, increase the contents of antioxidant enzyme SOD, CAT and GSH-PX, reduce the ROS levels, increase cell activity. By testing the apoptosis-related protein Bax, Bcl-2 and caspase-3, also proved that 10 μM SOG can improve ATO-induced cell apoptosis. So SOG can plays a role in detoxifying ATO cardiac toxicity.