BACKGROUND: Doxorubicin (DOX) is a potent chemotherapeutic agent used in the 
treatment of several tumors but its cardiac toxicity prevents its use at a 
maximum dose, representing an important problem. Increased reactive oxygen 
species (ROS) and imbalance in nitric oxide (NO) production have been implicated 
in the cardiotoxicity of doxorubicin. Hesperidin is a citrus bioflavonoid that 
possesses a potent antioxidant and NO modulating activities.
OBJECTIVES: Therefore, the aim of this study was to investigate the possible 
protective role of hesperidin against doxorubicin-induced cardiac toxicity.
METHODS: Four groups of animals were used in this study. First group served as a 
control and injected with the vehicle. Second group was given 200 mg/kg of 
hesperidin orally for seven consecutive days. The third group was injected with 
a single dose (20 mg/kg) of doxorubicin intraperitoneally and was sacrificed 
after 48 h. The fourth group was treated with hesperidin for seven days but on 
day five, 1-hour after hesperidin treatment, rats were injected with the single 
dose of doxorubicin. On day seven, the rats were scarified by decapitation. 
Blood was collected and processed for determination of serum lactate 
dehydrogenase (LDH), creatine kinase (CK) and NO. The hearts were removed and 
processed for both histopathological examination and determination of oxidative 
stress parameters like reduced glutathione (GSH), lipid peroxide (TBARS) levels 
and superoxide dismutase (SOD) activity.
RESULTS: Our results showed that doxorubicin produced severe cardiotoxicity as 
indicated from increase in serum LDH, CK activities and NO level. 
Histopathological examination of DOX-treated rats revealed degenerative changes 
in heart tissues. The significant decrease in GSH levels, SOD activity and 
increase in TBARS levels, indicated that DOX-induced cardiotoxicity was mediated 
through ROS generation. On the other hand, pretreatment of rats with hesperidin 
protected cardiac tissues against the cardiotoxic effects of doxorubicin as 
evidenced from amelioration of histopathological changes and normalization of 
cardiac biochemical parameters.
CONCLUSION: Hesperidin may have a protective effect against DOX-induced 
cardiotoxicity.