3,3’-Diindolymethane Ameliorates Adriamycin-induced Cardiac Fibrosis Via Activation Of A BRCA1-dependent Anti-oxidant Pathway

Adiramycin(ADR)that is a broad-spectrum chemotherapitic drug is used to treat with various of cancers.However, adriamycin and other anthracycline derivatives is limited due to dose-dependent cardiotoxicity. One of the most recognized toxicities of anthracycline derivatives is their strong promotion of oxidant formation. The oxygen radical that is induced by adriamycin could cause inflammation response which subsequently promotes cardiac fibrosis. Cardiac fibrosis is the main cause of adriamycin-induced toxicity.In our present studies, we observed the histopathologic change using HE staining; measured the disposition of collagen I in cardiac tissue by sirus red staining; assessed the production of BRCA1protein in cardiac tissue and fibroblast using western blotting and immunofluorescence; evaluated the expression level of a-SMAx collagen I、GPX3、GST mRNA using Q-PCR; estimated the content of ROS in fibroblast. The results were shown that DIM could reduce the level of α-SMA、collagen I in cardiac tissue and fibroblast. Additionally, we also proved that the level of BRCA1, GPX3and GST mRNA was markedly increased in mice that treated with adriamycin and DIM compared with that of mice administrated adriamycin alone. ROS that was induced by adriamycin in fibroblast was significantly suppressed by DIM. The above results suggested DIM could reverse adriamycin-induced cardiac fibrosis via a brcal-dependent anti-oxidant pathway.