Effect of high-dose cyclophosphamide gene expression profiles in cardiomyocytes of C57BL/6J mice

To clarify the mechanisms of cyclophosphamide (CY)-induced myocardial damage, we have analyzed the genome-wide expression profiles of C57BL/6J mice received CY, one of CY metabolites acrolein, and CY with N-acetyl cysteine (NAC). The microarray analysis revealed that the gene expression of L-type calcium channel (DHPR), ryanodine receptor 2 (RyR2), and Troponin C (TnC) were suppressed by CY administration. DHPR, RyR2 and TnC are responsible for control of intracellular calcium ion concentration and important for myocardial contraction. On the other side, the gene expression profiles after administration of acrolein differed from CY administration. Furthermore, the gene expression profiles after administration of NAC and CY, NAC did not inhibit the DHPR, RyR2 and TnC gene expression suppression. Six-week-old female mice were intraperitoneally injected with cyclophosphamide (CY, 400 mg/kg), acrolein (5 mg/kg), or N-acetyl cysteine (200 mg/kg) + CY once a daily for two days. Normal saline-treated mice were used as controls. Gene expression changes were measured 3 hours after the second dose. 3 independent studies were performed.