Effects of cyclophosphamide on the metabolism of primary hepatocytes in mice

Cyclophosphamide (CTX) is widely used as a chemotherapeutic agent in various cancers and in the mobilization and conditioning regimens for blood and marrow transplantation. However, hepatotoxicity resulting from CTX could contribute to prominent morbidity, with the underlying mechanism obscure. Since the liver is the central organ for metabolism, we thereby aimed to investigate the exact effect of CTX on the primary mouse hepatocytes and whether the metabolic pathways and metabolites are involved. The primary mouse hepatocytes were divided in the CTX group and the control group. CCK8, Annexin V and ELISA assays were employed. Our results indicated that CTX inhibited the vitality, impaired the morphology, reduced the numbers and accelerated the early apoptotic rate of the primary mouse hepatocytes. Moreover, CTX could lead to the change of key metabolic enzymes and metabolites involved in the three metabolisms pathways the in primary hepatocytes, which eventually caused the inhibition of anabolism in primary hepatocytes and promoted their catabolism. In conclusion, CTX exerted toxic effects on the primary mouse hepatocytes and affected the key metabolic enzymes and metabolites involved in the three metabolisms pathways in the mouse liver.