Activity of d,l-alpha-tocopherol (vitamin E) against cardiotoxicity induced by doxorubicin and doxorubicin with cyclophosphamide in mice.
The aim of this study was to investigate the cardioprotective activity of vitamin E against doxorubicin alone and doxorubicin in combination with cyclophosphamide in mice. Female BalbC/NIH mice were treated with vitamin E (100 IU/kg, orally) 24 hr before single bolus doses of doxorubicin (10 mg/kg, intravenously), or doxorubicin and cyclophosphamide (150 mg/kg, intraperitoneally). Non-treated animals served as negative controls, while positive control groups received doxorubicin or doxorubicin and cyclophosphamide. For evaluation, serum enzyme activity of aspartate aminotransferase (AST), lactate dehidrogenase (LDH), alpha-hydroxybutirate dehydrogenase (alpha-HBDH), and creatine kinase (CK) at 48 hr and histopathology examination of the heart tissue (Billigham rules) at 1.5 and 3 months followed to treatments were used. In sera of mice treated with vitamin E prior to doxorubicin, the creatine kinase and % alpha-HBDH activity were significantly reduced, compared to positive control. Histopathology changes (scored as 1.5 at 1.5 and 3 months respectively) were not significant compared to negative control at both time points of examination. In animals which received vitamin E before doxorubicin and cyclophosphamide, none of the serum enzymes was significantly reduced compared to positive control, but non-significant increase in AST and creatine kinase activity was detected (3% and 16.57% respectively). The degree of myocardial damage was significantly higher compared to non-treated group (2.0 and 2.5 at 1.5 and 3 months respectively). Current results show that vitamin E in single oral dose failed to inhibit acute cardiotoxic activity of doxorubicin, but suspended further progression of the heart muscle damage over the time. On the contrary, vitamin E did not attain any cardioprotection against doxorubicin and cyclophosphamide in combination.
Bjelogrlic
Snezana K
SK
Department of Experimental Oncology, National Cancer Research Center, Belgrade, Serbia & Montenegro. zanab@bitsyu.net
Radic
Jelena
J
Jovic
Viktor
V
Radulovic
Sinisa
S
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004798:Enzymes / Q000097:blood; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D014810:Vitamin E / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000975:Antioxidants; D004798:Enzymes; D014810:Vitamin E; D004317:Doxorubicin; D003520:Cyclophosphamide