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PMID: 1464156 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Prevention of doxorubicin-induced myocardial and haematological toxicities in rats by the iron chelator desferrioxamine.

Cancer chemotherapy and pharmacology ·Vol. 31 ·No. 3 ·1992-00-00 ·Pages 200-4

al-Harbi MM, al-Gharably NM, al-Shabanah OA, al-Bekairi AM, Osman AM, Tawfik HN

Abstract

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.

MeSH Terms
Animals Aspartate Aminotransferases/blood,drug effects Blood/drug effects Blood Cell Count/drug effects Creatine Kinase/blood,drug effects Deferoxamine/therapeutic use Doxorubicin/toxicity Drug Evaluation, Preclinical Heart/drug effects Hemoglobins/drug effects Isoenzymes L-Lactate Dehydrogenase/blood,drug effects Myocardium/enzymology,pathology Rats Rats, Wistar Time Factors
Chemicals
Hemoglobins Isoenzymes Doxorubicin L-Lactate Dehydrogenase Aspartate Aminotransferases Creatine Kinase Deferoxamine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
al-Harbi M M
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
al-Gharably N M
al-Shabanah O A
al-Bekairi A M
Osman A M
Tawfik H N
References (21)
21 references, click to expand
  1. Effects of ICRF-187 on the cardiac and renal toxicity of epirubicin in spontaneously hypertensive rats.
    Cancer Chemother Pharmacol. 1989;23(5):269-75 PMID: 2495862
  2. Adriamycin (NSC-123,127): a new antibiotic with antitumor activity.
    Cancer Chemother Rep. 1969 Feb;53(1):33-7 PMID: 5772652
  3. Effect of aspartate and glutamate on experimental myocardial infarction in rats.
    Indian J Exp Biol. 1989 Jul;27(7):621-4 PMID: 2632387
  4. Reduction in the diabetogenic effect of alloxan in mice by treatment with the antineoplastic agent ICRF-187.
    Res Commun Chem Pathol Pharmacol. 1981 Sep;33(3):509-23 PMID: 7036302
  5. Adriamycin-induced cardiotoxicity (cardiomyopathy and congestive heart failure) in rats.
    Cancer Res. 1977 Aug;37(8 Pt 1):2705-13 PMID: 872096
  6. Effect of diethyldithiocarbamate on toxicity of doxorubicin, cyclophosphamide and cis-diamminedichloroplatinum (II) on mice haemopoietic progenitor cells.
    Br J Cancer. 1989 Mar;59(3):371-4 PMID: 2539178
  7. Prevention of doxorubicin myocardial toxicity in mice by reduced glutathione.
    Cancer Res. 1986 May;46(5):2551-6 PMID: 3697994
  8. Mechanism of the protective activity of ICRF-187 against alloxan-induced diabetes in mice.
    Res Commun Chem Pathol Pharmacol. 1986 Jun;52(3):341-60 PMID: 3090662
  9. A general mechanism for microsomal activation of quinone anticancer agents to free radicals.
    Cancer Res. 1978 Jun;38(6):1745-50 PMID: 25710
  10. Model systems for cardiotoxic effects of anthracyclines.
    Antibiot Chemother (1971). 1978;23:255-70 PMID: 348084
  11. The role of iron in oxygen radical mediated lipid peroxidation.
    Chem Biol Interact. 1989;71(1):1-19 PMID: 2550151
  12. Adriamycin-induced cardiac damage in the mouse: a small-animal model of cardiotoxicity.
    J Natl Cancer Inst. 1975 Jul;55(1):191-4 PMID: 1159813
  13. Clinical evaluation of adriamycin, a new antitumour antibiotic.
    Br Med J. 1969 Aug 30;3(5669):503-6 PMID: 5257148
  14. Oxidative destruction of erythrocyte ghost membranes catalyzed by the doxorubicin-iron complex.
    Biochemistry. 1982 Apr 13;21(8):1707-12 PMID: 6805506
  15. Protective effect of ICRF-187 on doxorubicin-induced cardiac and renal toxicity in spontaneously hypertensive (SHR) and normotensive (WKY) rats.
    Toxicol Appl Pharmacol. 1988 Jan;92(1):42-53 PMID: 3124293
  16. Myocardial damage induced by doxorubicins: hydroperoxide-initiated chemiluminescence and morphology.
    Free Radic Biol Med. 1990;8(3):259-64 PMID: 2341055
  17. Inhibition of creatine kinase activity by Ca2+ and reversing effect of ethylenediaminetetraacetate.
    Clin Chem. 1978 Jan;24(1):177-8 PMID: 412618
  18. Effect of desferrioxamine on reperfusion damage of rat heart mitochondria.
    S Afr Med J. 1990 Sep 1;78(5):263-5 PMID: 2392723
  19. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases.
    Am J Clin Pathol. 1957 Jul;28(1):56-63 PMID: 13458125
  20. Adriamycin affects glomerular renal function: evidence for the involvement of oxygen radicals.
    Free Radic Res Commun. 1989;7(3-6):195-203 PMID: 2531111
  21. Adriamycin. A new anticancer drug with significant clinical activity.
    Ann Intern Med. 1974 Feb;80(2):249-59 PMID: 4590654
Article Info
Journal
Cancer chemotherapy and pharmacology
Abbr.
Cancer Chemother Pharmacol
ISSN
0344-5704
Published
1992-00-00
Pages
200-4
Language
English
Region
Germany
NLM ID
7806519
Subset
IM
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