Electrocardiographic and biochemical evidence for the cardioprotective effect of vitamin E in doxorubicin-induced acute cardiotoxicity in rats.
OBJECTIVE
Cardiotoxicity is a major side effect limiting the use of doxorubicin, a potent chemotherapeutic agent, in the treatment of pediatric neoplastic diseases. The effect of vitamin E in doxorubicin-induced cardiotoxicity in rats has been studied.


METHODS
Eighteen Wistar male rats (age 60 - 100 days, weighing 175 - 260 g) were divided into three groups of six: group A (controls); group B (doxorubicin-treated rats); and group C (pretreatment with a high dose of vitamin E followed by doxorubicin treatment). The weights of the rats were measured daily. The rats were sacrificed seven days after the last dose of doxorubicin injection by an overdose of ether. Electrocardiogram (ECG) tracings were recorded before sacrificing the rats. The ECG tracings were then evaluated for rate and rhythm disorders by assessing the PR, ST, and QT intervals. In group B rats ECG tracings were taken three days after the completion of doxorubicin treatment, while in group C rats they were taken at the end of 2 weeks of vitamin E pretreatment and again 3 days after the completion of doxorubicin treatment. Serum levels of creatine phosphokinase (CPK-MB), lactic dehydrogenase (LDH), and serum glutamic oxaloacetic transaminase (SGOT) were assessed from an intracardiac blood sample taken at the time of sacrificing the rat.


RESULTS
Mean weight ranged from 205 - 226 g. Mean total dose of doxorubicin in groups B and C ranged from 36 - 38 mg. The PR intervals in the three groups were recorded as 0.006, 0.070, 0.057 s for groups A, B, and C, respectively (p = 0.0024) and the QT interval as 0.023, 0.120, 0.088 s in groups A, B, and C, respectively (p = 0.00089). The ST elevation due to doxorubicin toxicity was significantly reversed by vitamin E treatment. The difference in the levels of CPK-MB and LDH between the three groups was found to be statistically significant. Serum SGOT levels also varied between the three groups but were not statistically significant.


CONCLUSIONS
Vitamin E pretreatment prevented the PR, QT, and ST segment changes caused by doxorubicin. Vitamin E treatment helped to decrease the levels of CPK-MB and LDH that were increased due to myocardial damage caused by the doxorubicin. There is sufficient evidence to believe that vitamin E protects the rat myocardium from doxorubicin-induced damage.
Puri
A
A
The Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India.
Maulik
S K
SK
Ray
R
R
Bhatnagar
V
V
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology*; D004317:Doxorubicin / Q000009:adverse effects*; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014810:Vitamin E / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D014810:Vitamin E; D004317:Doxorubicin