Thymoquinone Prevents Doxorubicin-induced Hepatic-injury by Mitigating the Impairment of Mitochondrial Respiration and Electron Transport

Abstract

Doxorubicin (DXR) is an anthracycline antibiotic that is commonly used in cancer treatment. The purpose of this study was to see if Thymoquinone (THY) could reduce the hepatotoxic effects of doxorubicin. All animals were divided into four groups: control (Phosphate buffer i.p. 0.5mlkg -1 /day), THY (10mgkg -1 /i.p/daily), doxorubicin (20mgkg -1 /i.p/single dose), THY (10mgkg -1 /i.p/daily) + DOX(20mgkg -1 /i.p/single dose on Day 7). Changes in hepatic enzymes in serum ALT, AST, and GGT, as well as tests for free radical metabolism enzymes such as Cu, Zn-SOD, CAT, and MDA were carried out in all animals that received treatments. In addition, the inflammatory markers IL-6, Nf-kB, and TNF-alpha were measured in liver tissue homogenate. Caspase, an apoptosis marker, was also measured. The liver enzymes were significantly elevated in DOX treated rats as compared to all treated groups. Thymoquinone pretreatment significantly reduced the level of hepatic enzymes as compared to DOX. Comparison of the DOX-treated group to the control group showed that SOD and catalase activities rose significantly. In the DOX-treated group, malondialdehyde levels were higher than in the control and all-treatment groups, respectively (P<0.05). The THY + DOX group had lower levels of malondialdehyde, SOD, and catalase activity than the DOX-group (P<0.05). Anti-inflammatory markers , as well as Caspase 3 (p<0.0001), reduced in THY-treated rats, were found to be significantly lower in THY-treated rats (P<0.0001). Biochemical findings were supported by histopathological studies. We conclude that by modulating ROS, inflammation, and apoptosis, thymoquinone significantly reduces DOX-induced hepatotoxicity in rats.