Prevention of doxorubicin-induced myocardial and haematological toxicities in rats by the iron chelator desferrioxamine.
Biochemical and histopathological evaluations of the protective effects of the iron-chelator desferrioxamine against the cardiac and haematological toxicities of doxorubicin in normal rats were carried out. A single dose of doxorubicin (15 mg/kg, i.v.) caused myocardial damage that manifested biochemically as an elevation of serum cardiac enzyme [glutamic oxaloacetic transaminase (GOT), lactic dehydrogenase (LDH) and creatine phosphokinase (CPK)] and cardiac isoenzyme levels and histopathologically as a swelling and separation of cardiac muscle fibers. Doxorubicin caused severe leucopenia and decreases in red blood cell counts and haemoglobin concentrations at 72 h after its administration. Desferrioxamine treatment (250 mg/kg, i.p.) carried out 30 min before doxorubicin administration protected the heart and blood elements from the toxic effects of doxorubicin as indicated by the recovery of levels of cardiac enzymes and isoenzymes and of red blood cell counts to normal values and by the absence of significant myocardial lesions. The findings of this study suggest that desferrioxamine can potentially be used clinically to prevent doxorubicin-induced cardiac and haematological toxicities.
al-Harbi
M M
MM
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
al-Gharably
N M
NM
al-Shabanah
O A
OA
al-Bekairi
A M
AM
Osman
A M
AM
Tawfik
H N
HN
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D001769:Blood / Q000187:drug effects*; D001772:Blood Cell Count / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood / Q000187:drug effects; D003676:Deferoxamine / Q000627:therapeutic use*; D004317:Doxorubicin / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D006321:Heart / Q000187:drug effects*; D006454:Hemoglobins / Q000187:drug effects; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D006454:Hemoglobins; D007527:Isoenzymes; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase; D003676:Deferoxamine