Abatement by naringenin of doxorubicin-induced cardiac toxicity in rats.
BACKGROUND
Doxorubicin is one of the most active cytotoxic agents in current use. It has proven efficacy in various malignancies either alone or combined with other cytocidal agents. The clinical usefulness of the anthracycline drug has been precluded by cardiac toxicity. Many therapeutic interventions have been attempted to improve the therapeutic benefits of the drug. Few, however, have been efficacious in this setting.


OBJECTIVE
We have addressed in the current study the possible protective effects of naringenin, a flavonoid known to have anti-oxidant properties, on doxorubicin-induced cardiac toxicity in male Swiss albino rats.


METHODS
Forty male Swiss albino rats were used in this study. Naringenin (25 mg/kg body weight) was administered daily by gavage for 7 consecutive days before a cumulative single dose of doxorubicin (15 mg/kg body weight, ip).


RESULTS
Doxorubicin induced marked biochemical alterations characteristic of cardiac toxicity including, elevated activities of serum total lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), enhanced lipid peroxidation measured as malondialdehyde (MDA). The anthracycline drug has also reduced the cardiac enzymatic activities of superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT). Besides, it reduced significantly the reduced glutathione (GSH) level, but it increased the total NO content in heart tissue. Prior administration of naringenin ahead of doxorubicin challenge ameliorated all these biochemical markers.


CONCLUSIONS
Taken together, one could conclude that naringenin has a protective role in the abatement of doxorubicin-induced cardiac toxicity that resides, at least in part, on its anti-radical effects and regulatory role on NO production.
Arafa
Hossam M
HM
The Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, National Cancer Institute, Cairo University.
Abd-Ellah
Mohamed F
MF
Hafez
Hafez F
HF
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000975:Antioxidants / Q000627:therapeutic use*; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D003402:Creatine Kinase / Q000097:blood / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects*; D044950:Flavanones / Q000627:therapeutic use*; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D006331:Heart Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D044950:Flavanones; D009569:Nitric Oxide; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D003402:Creatine Kinase; C005273:naringenin