|Nascimento, Maria Carolina|
|Ferreira, Ana Lucia|
Submitted to: Human and Experimental Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/11/2011
Publication Date: 10/20/2011
Citation: Nascimento, M., Matsubara, B.B., Matsubara, L.S., Correa, C.R., Pereira, E.J., Moreira, P.L., Carvalho, F.A., Burini, C.H., Padovani, C.R., Yeum, K., Ferreira, A.A. 2011. Pharmacological dose of alpha-tocopherol induces cardiotoxicity in Wistar rats determined by echocardiography and histology. Human and Experimental Toxicology. 30(10):1540-1548. Interpretive Summary: The effect of a supraphysiological dose (greater than normally present in the body) of vitamin E on heart health was studied in Wistar rats. Animals were randomly assigned to either the control or the vitamin E group. Animals received corn oil or vitamin E dissolved in corn oil for a 7-week period. Rats then underwent an exam using a type of ultrasound test (i.e. echocardiogram) to compare heart muscle tissue anatomy at the end of the study period. Vitamin E levels were also assessed. As compared to the control group, the vitamin E-supplemented group showed substantially lower body weight and total heart weight; heart muscle tissue anatomy displayed functional disabilities. The vitamin E uptake in target tissue was confirmed by determination of vitamin E concentrations in heart tissue. The current study indicates that supplementation with supraphysiological levels of vitamin E can induce toxicity in the heart of healthy rats.
Technical Abstract: The effect of pharmacological dose of alpha-tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (alpha-tocopherol, n = 11) group. Animals received corn oil (C) or alpha-tocopherol dissolved in corn oil (250 mg alpha-tocopherol/[kg body wt/day]) (E) by gavage for a 7-week period. Rats underwent echocardiogram and were analyzed for cardiomyocyte histology and cardiac alpha-tocopherol absorption at the end of the study period. As compared to the C group, alpha-tocopherol-supplemented group showed significantly (p < 0.05) lower body weight (E, 412.8 g vs C, 480.3 g) and total cardiac weight (E, 0.94 g vs C, 1.08 g); cardiomyocyte histological impairment; smaller left ventricle (LV) (LV end-diastolic diameter (E, 7.22 mm vs C, 7.37 mm), lower LV systolic [left ventricle fractional shortening (E, 47.6% vs C, 53.6%) and ejection fraction ratio (E, 85.4 vs C, 89.9)] and diastolic [early peak velocities of diastolic transmitral flow (E, 64.6 cm/sec vs C, 75.1 cm/sec)] function. The alpha-tocopherol uptake in target tissue was confirmed by determination of alpha-tocopherol concentration medians in cardiac tissue (E, 109.91 nmol/kg vs C, 52.09 nmol/kg). The current study indicates that pharmacological dose of alpha-tocopherol supplementation can induce cardiotoxicity in healthy rats.