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Journal of Indian Association of Pediatric Surgeons
     Journal of Indian Association of Pediatric Surgeons
Official journal of the Indian Association of Pediatric Surgeons         
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Year : 2001  |  Volume : 6  |  Issue : 4  |  Page : 112-118

Cardioprotective effect of Vitamin E in doxorubicin induced acute cardiotoxicity in Rats


Departments of Pediatric Surgery, Pharmacology and Pathology, All Institute Of Medical Sciences, New Delhi -110029, India

Correspondence Address:
A Puri
Departments of Pediatric Surgery, Pharmacology and Pathology, All Institute Of Medical Sciences, New Delhi -110029
India
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Source of Support: None, Conflict of Interest: None


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ABSTRACT: Background/aims: Doxorubicin, a potent chemo-therapeutic agent for treatment of pediatric neoplastic diseases, has a major side effect limiting its use-cardiotoxicity. The role of vitamin E in doxorubicin induced cardiotoxicity in rats has been studied. Methods: Eighteen Wistar male rats (age 60-100 days, weighing 175-260g) were divided into 3 groups of 6 each: group A (controls they received neither doxorubicin nor vitamin E); group B (doxo-rubicin treated rats-the experimental model of doxorubicin induced acute cardiotoxicity was created by giving intraperitoneal injection of doxorubicin 4 mg/kg for 7 days); group C (received pre-treatment with high dose vitamin e, 1000 IU/kg for 2 weeks by enteral route, followed by intraperitoneal doxorubicin injection, 4mg/kg, for 7 days. During these 7 days vitamin E supplementation was continued as earlier). The weights of the rats were measured daily. The rats were sacrificed 7 days after the last dose of doxorubicin injection by an overdose of ether. Rat heart tissues were taken for estimation of thiobarbituric acid reactants (TBARS) and for histopathological evaluation. Histological evaluation of rat heart was done by light and transmission electron microscopy. Special stains eg Masson's Trichrome and VanGieson were also done. Results: Mean weight of rats ranged from 205-226g. Mean total dose of doxorubicin in groups B & C: 36-38mg. Mean total dose of vitamin E in group C: 680mg (range 525-780mg). Weight loss was noted 2-3 days after doxorubicin injection in all 6 rats of group B and in 2 rats of group C (p=0.015). TBARS level in ng/g in the 3 groups were 65.07, 235.71 and 98.08 in groups A, B and C respectively (p=0.00511). Light microscopy: Focal and mild myocarditis and fibrosis were seen in 2 rats of group B. Sarcoplasmic vacuolization was not seen in any of the 3 groups. Light microscopy findings were statistically not significant. Electron microscopy showed sarcotubular dilatation and extracellular collagen deposition in 50-60 percent of rats in group B (p=0.04, 0.005). Lipid vacuolization, myofibril loss and mitochondrial disarray and dilatation differences were not statistically significant. Conclusion: Vitamin E pre-treatment prevented the TBARS elevation and the sarcotubular dilatation extracellular collagen deposition caused by doxorubicin induced oxidant damage. There is sufficient evidence to believe that vitamin E protects the rat myocardium from doxorubicin induced damage.






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