Thymoquinone Ameliorates Doxorubicin-Induced Cardiotoxicity in Swiss Albino Mice by Modulating Oxidative Damage and Cellular Inflammation

Abstract

Thymoquinone is the active constituent of Nigella sativa, having antioxidant and anti-inflammatory actions. In present study, we have analyzed the effects of thymoquinone on doxorubicin (DOX) induced cardiotoxicity in mice. In this experiment, thirty mice (25–35 gm) were divided into five groups (Groups A, B, C, D, and E) each containing six animals. Normal saline was given to a control group (Group A) for 14 days. Cardiotoxicity was induced by DOX (15 mg/kg, i.p.) in Group B, once on the 13th day of the study, and Groups C and D also received DOX (15 mg/kg, i.p.) and were then treated with thymoquinone (10 and 20 mg/kg, b/w, p.o.), respectively, for 14 days. Group E was given only thymoquione (20 mg/kg b/w, p.o.). A blood serum marker (AST, ALT, CK-MB, and LDH) and oxidative stress marker (LPO, GSH, CAT, SOD, GPx, GR, and GST) were evaluated. Results revealed that serum enzyme marker like aspartate aminotransferase (AST), creatinine kinase-MB (CKMB), and lactate dehydrogenase (LDH) were significantly elevated in Group B as compare to Group A. Similarly, the oxidative stress marker lipid peroxidation (LPO) was also elevated in Group B while the antioxidant enzyme catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase (CAT, SOD, GPx, GR, and GST) were also decreased in Group B. The treatment with thymoquinone 10 and 20 mg/kg resulted in a significant decrease in the serum marker and increase in the antioxidant enzymes. In this study, we have found that thymoquinone prevented DOX-induced cardiotoxicity by accelerating heart antioxidant defense mechanisms and down regulating the LPO levels towards normalcy in Groups C and D. The effect of doxorubicin increases the inflammatory cytokine (IL2) in Group B as compared to Group A, and it overcomes by the thymoquinone in Groups C and D. Thus, thymoquinone may have utility as a potential drug for cardiomyopathy.

Cardioprotective Potential of Murraya koenigii (L.) Spreng. Leaf Extract against Doxorubicin‐Induced Cardiotoxicity in Rats

“…However, the treatment with aqueous Murraya leaf extract increases SOD and catalase level suggesting its antioxidant and ROS-scavenging nature. Not only the present study but also many previous studies on the protective effect against doxorubicin-induced cardiotoxicity based on the antioxidant property have shown a similar effect on SOD and the catalase activity [47,48,51,52,54]. Total antioxidant status of the doxorubicin-treated animals was greatly reduced in the present study suggesting that doxorubicin treatment causes depletion of antioxidants in the body.…”

“…leaf extract significantly reduced the lipid peroxidation suggesting the antioxidant potential of the plant. Many previous studies on natural products or other compounds with high amount of antioxidants have shown a reduction of lipid peroxidation in doxorubicin-induced cardiotoxicity [27,51,52,54,55].…”

“…A study done by Chen et al has shown that diosgenin, a steroidal saponin of Dioscorea opposita, also has the ability to increase the GSH and GPx level decreased by doxorubicin treatment in Balb/c mice [48]. ymoquinone, an active constituent of Nigella sativa, having antioxidant and anti-inflammatory actions was also shown to protect against doxorubicin-induced cardiotoxicity in mice with increased value of antioxidant markers including GSH, GPx, and GR activities [52]. SOD, catalase, and GPx are three key enzymes considered as the first line defense antioxidant enzymes which dismutate superoxide radical and breakdown hydrogen peroxides and hydroperoxide to harmless molecules such as H 2 O 2 /alcohol and O 2 [53].…”

“…Inside the cardiomyocytes, doxorubicin undergoes redox cycling and produces semiquinone radical which is oxidized back to its original form by reducing molecular oxygen to form superoxide radicals [4]. SOD is a metaloenzyme which catalyzes the conversion reaction of superoxide radicals to hydrogen peroxide [52].…”

Nrf2‑dependent antioxidant response mediated the protective effect of tanshinone IIA on doxorubicin‑induced cardiotoxicity

“…1 ). Serum myocardial enzymes (AST, LDH, CK and CK-MB) are the important indexes that reflect the extent of myocardial injury ( 18 ). As presented in Table III , DOX significantly increased the activity of all enzymes compared with controls, indicating cardiotoxicity.…”