Effect of troxerutin on oxidative stress and expression of genes regulating mitochondrial biogenesis in doxorubicin-induced myocardial injury in rats

Because of limitation of doxorubicin (DOX) clinical application in chemotherapy due to its cardiotoxicity, finding new strategies to reduce DOX challenge and improve patients’ outcomes is crucial. Due to positive cardiovascular impacts of troxerutin (TXR), here we have investigated the effect of TXR on DOX-induced cardiotoxicity by evaluating the myocardial oxidative stress and expression of genes regulating mitochondrial biogenesis. Male Wistar rats (250–300 g) were randomly allocated into four groups: control, TXR, DOX, and TXR + DOX. Troxerutin (150 mg/kg) was orally administrated once a day through a gavage tube for 4 weeks before DOX challenge. The TXR-treated and time-matched control rats received intraperitoneal injection of DOX (20 mg/kg). Three days after DOX challenge, the left ventricular samples were obtained to determine the expression of genes regulating mitochondrial biogenesis via real-time PCR. Myocardial creatine kinase (CK-mB), oxidative stress markers, and mitochondrial function (generation of reactive oxygen species or ROS and ATP levels) were also evaluated using commercial kits and spectrophotometric and fluorometric methods. DOX administration significantly increased the levels of CK-mB, malondialdehyde (MDA), and mitochondrial ROS levels, while reduced the cellular ATP production and expression levels of SIRT-1, PGC-1α, and NRF-2 as well as superoxide dismutase, glutathione peroxidase, and catalase activity in comparison to control group ( P