Effect of MitoQ on mitochondrial function and expression of genes regulating mitochondrial biogenesis in rats with doxorubicin-induced cardiotoxicity

Abstract

Doxorubicin (DOX) is an effective chemotherapeutic agent; however, its application is limited due to its cardiotoxic effects. This study aimed to investigate the effect of MitoQ antioxidants on DOX-induced cardiotoxicity, mitochondrial function, and the expression of genes involved in mitochondrial biogenesis. Materials and methods: In this study, 24 male rats were be divided into four groups (6 rats in each group): healthy control group (Control), the group receiving DOX (DOX), the group receiving MitoQ (MitoQ) and the group receiving doxorubicin and MitoQ (DOX+MitoQ). DOX was administrated in 6 doses (2 mg/kg/48hr) intraperitoneally during 12 days (cumulative dose: 12 mg/kg) and MitoQ (10 mg/kg/day) was injected intraperitoneally for four weeks before doxorubicin injection. One week after the injection of the last dose of doxorubicin, blood was taken from the portal vein, and the hearts of the rats were removed for experiments. Serum LDH levels, mitochondrial membrane potentials, and mitochondrial reactive oxygen species (ROS) production were measured. The expression level of genes involved in mitochondrial biogenesis (SIRT-1, PGC-1α, NRF2) was determined using the real-time PCR method. Results: MitoQ pretreatment led to a significant decrease in serum LDH levels of DOX-treated mice. MitoQ also increased the mitochondrial membrane potential and decreased the production of ROS in the left ventricular tissue of DOX-treated rats. Downregulation of NRF2, PGC-1α and SIRT-1 genes, which are involved in mitochondrial biogenesis, was also observed in the MitoQ + DOX group. No significant changes were observed in the mentioned parameters in the MitoQ group compared to the control group.