Protective effect of Spirulina against doxorubicin-induced cardiotoxicity.
The generation of reactive oxygen species and mitochondrial dysfunction has been implicated in doxorubicin (DOX)-induced cardiotoxicity. The aim of the present study was to determine whether Spirulina, a blue-green algae, could serve as a cardioprotective agent during DOX treatment in a mouse model. Mice were treated with DOX (4 mg/kg bw, intraperitoneally), weekly, for 4 weeks. Spirulina was administered orally for 3 days twice daily, then for 7 weeks along with the four equal injections of DOX. Cardiotoxicity was assessed, at 3 weeks after the end of the DOX-treatment period, by mortality, volume of ascites, liver congestion, oxidative stress and ultrastructural changes of heart tissue. The DOX-treated animals showed higher mortality (53%) and more ascites. Myocardial damage, as assessed by ultrastructural changes, showed loss of myofibrils, cytoplasmic vacuolization and mitochondrial swelling. Myocardial superoxide dismutase and glutathione peroxidase activities were decreased and lipid peroxidation was increased. Pretreatment with Spirulina significantly protected the mice from DOX-induced cardiotoxic effects as evidenced from lower mortality (26%), less ascites, lower levels of lipid peroxidation, normalization of antioxidant enzymes and ultrastructural studies showing minimal damage to the heart. In vitro cytotoxic studies using ovarian cancer cells demonstrated that Spirulina did not compromise the anti-tumor activity of doxorubicin. These results suggest that Spirulina has a protective effect against cardiotoxicity induced by DOX and it may, therefore, improve the therapeutic index of DOX.
Khan
Mahmood
M
Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, India.
Shobha
Jagdish Chandra
JC
Mohan
Iyyapu Krishna
IK
Naidu
Madireddi Umamaheswara Rao
MU
Sundaram
Challa
C
Singh
Shashi
S
Kuppusamy
Periannan
P
Kutala
Vijay Kumar
VK
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000458:Cyanobacteria; D004317:Doxorubicin / Q000009:adverse effects* / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006321:Heart / Q000187:drug effects*; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects; D010798:Phycocyanin / Q000378:metabolism; D053545:Spirulina; D013481:Superoxides / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D001426:Bacterial Proteins; D010798:Phycocyanin; D013481:Superoxides; D004317:Doxorubicin