Hesperidin alleviates doxorubicin-induced cardiotoxicity in rats.
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.


OBJECTIVE
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.


CONCLUSIONS
Hesperidin may have a protective effect against DOX-induced cardiotoxicity.
The Department of Pharmacology & Toxicology, Al-Azhar University, Assiut, Egypt. IlhabPharma@yahoo.com
Ihab T
IT
Abdel-Raheem
Ahmed A
AA
Abdel-Ghany
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D003402:Creatine Kinase / Q000097:blood; D004317:Doxorubicin / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced / Q000188:drug therapy*; D006569:Hesperidin / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D008054:Lipid Peroxides; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D004317:Doxorubicin; D006569:Hesperidin; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D003402:Creatine Kinase; D005978:Glutathione