Effect of methimazole treatment on doxorubicin-induced cardiotoxicity in mice.
The major limiting factor in long-term administration of doxorubicin is the development of cumulative dose-dependent cardiomyopathy and congestive heart failure that limit the use of this drug. The present study was undertaken to find out the chemo protective role of methimazole against doxorubicin-induced cardiotoxicity in experimental animals. In the present study, doxorubicin treatment in a dose of 3mg/kg, i.p., every other day for six doses showed a significant 2.6-, 3- and 10.5-fold increase in the cardiac enzyme activities CK-MB and LDH and troponin-I, respectively, in the serum of the animals. Histopathological investigation of heart tissues showed swollen muscle fibers with interstitial edema and inflammatory exudate. Pretreatment of the animals with methimazole at a dose level of 40 mg/kg, i.p., 30 min before doxorubicin, returned the cardiac enzyme levels to nearly normal value with partial reversal of the inflammatory lesions and the swollen muscle fibers induced by doxorubicin. Moreover, methimazole pretreatment, decreased the doxorubicin level in the heart tissues with a significant increase in plasma level and non significant effect on doxorubicin level in tumor cells. At the same time, methimazole pretreatment did not significantly interfere with the antitumor activity of doxorubicin.
Osman
Abdel-Moneim M
AM
College of Medicine, Pharmacology Dept, King Abdel-Aziz University, Jeddah, Saudi Arabia. moneimosman@hotmail.com
Nemnem
Marwa M
MM
Abou-Bakr
Amany A
AA
Nassier
Omimah A
OA
Khayyal
Mohamed T
MT
D000818:Animals; D021461:Animals, Outbred Strains; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000633:toxicity*; D013956:Antithyroid Agents / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000473:pathology; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D052279:Creatine Kinase, MB Form / Q000097:blood; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000633:toxicity*; D004354:Drug Screening Assays, Antitumor; D004359:Drug Therapy, Combination; D005260:Female; D006321:Heart / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008713:Methimazole / Q000494:pharmacology*; D051379:Mice; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009368:Neoplasm Transplantation; D013963:Thyroid Hormones / Q000097:blood; D019210:Troponin I / Q000097:blood
D000903:Antibiotics, Antineoplastic; D013956:Antithyroid Agents; D013963:Thyroid Hormones; D019210:Troponin I; D008713:Methimazole; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D052279:Creatine Kinase, MB Form