The effect of coenzyme Q10 on mitochondrial function and biogenesis in rats with doxorubicin-induced cardiotoxicity

Abstract

Doxorubicin (DOX) is a widely used chemotherapy drug that is highly effective in the treatment of many types of cancer. However, its use is limited due to its cardiotoxicity, which can lead to heart failure, arrhythmia, and even death. The mechanisms of DOX-induced cardiotoxicity are not fully understood, but production of reactive oxygen species (ROS), DNA damage, and mitochondrial dysfunction play key roles. Coenzyme Q10 (CoQ10) is an antioxidant that has important cardioprotective effects. This study aimed to investigate the effects of CoQ10 on cardiac histopathological changes and mitochondrial function and biogenesis in rats suffering from doxorubicin-induced cardiotoxicity. Methods: Forty adult male Wistar rats (250-300 grams) were used in this study. Rats were randomly divided into four groups: 1. Control group: received only normal saline with a volume of 2 mg/kg , every other day for 12 days through intraperitoneal injection.; 2. DOX group: received doxorubicin (2 mg/kg) through intraperitoneal injection ,every other day for 12 days; 3. Q10 group: received coenzyme Q10 (10 mg/kg) through intraperitoneal injection for 21 days; 4. Q10 + DOX group: received coenzyme Q10 (10 mg/kg) through intraperitoneal injection for 21 days in a row, on the ninth day of receiving Q10,in addition to receiving Q10, received doxorubicin (2 mg/kg) through intraperitoneal injection ,every other day for 12 days. One day after the last injection, all the animals were anesthetized and first blood samples were taken and then hearts were dissected and left ventricular tissue was prepared for histopathological examination, biochemical and molecular analysis.

Results: The results of this study showed that DOX caused significant structural damage to heart tissue and increased the release of LDH compared to the control group. Also, in the DOX group compared to the control group, the amount of mitochondrial ROS production in the heart tissue increased and the mitochondrial membrane potential and expression of genes SIRT3, PGC-1α and NRF2 decreased. Despite this, pretreatment with coenzyme Q10 was able to significantly reduce the tissue damage caused by DOX and significantly improved the indices of mitochondrial function and the expression of genes involved in mitochondrial biogenesis compared to the DOX group.