Author + information
- Xiao Liu,
- Yang Yang,
- Xianghui Ma,
- Yuchen Qian and
- Xiaoying Wang
Doxorubicin (Dox) is anti-tumor drug which is widely used in clinic. It has a wide range of biological and chemical effects for human body. However, Dox also could produce some serious adverse reactions, such as cardiac toxicity, and violent cytotoxic function. The aim of this study was to explore the mechanism of cardiac toxicity induced by Dox.
Sixteen wistar rats (250 ± 10g) were randomly divided into 2 groups, control group: intraperitoneal injection of saline; Dox group: intraperitoneal injection of Dox (3mg/kg), once every two days. Medicine was taken 4 times totally, and accumulative dosage of Dox was 12mg/kg. Then, the spleens were isolated from rats. By the application of Agilent Rat Gene Expression, we identify the differentially expressed genes. After that, we imported the differentially expressed genes into Ingenuity Pathways Analyses (IPA) to screen the pathways (P-value ＜＝ 0.05) and genes related to cardiac toxicity reduced by Dox.
In summary of IPA, we predicted Dox could induce cardiotoxicity, such as cardiac infarction, heart failure, cardiac hypertrophy, cardiac congestive cardiac failure and congenital heart anomay. In the part of diseases and function, it was also predicted that Dox could lead to some cardiovascular diseases, for instance, arteriosclerosis, acute coronary syndrome and infarction. From the analysis of canonical pathways, atherosclerosis signaling pathway was related to Dox cardiac injury and there were 16 genes regulated this pathway, which mainly included CCR3, ALOX15, IL1A, CXCL12.
Our study indicated that Dox could induce cardiac toxicity mainly by atherosclerosis signaling pathway during treatment, and the genes of CCR3, ALOX15, IL1A, CXCL12 involved in Dox cardiac injuy.