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Diazepam potentiates the protective effect of simvastatin against psychological stress- enhancement of doxorubicin cardiomyopathy

Author(s): Nayira A. Abdel Baky | Azza A. Ali

Journal: International Journal of Academic Research
ISSN 2075-4124

Volume: 1;
Issue: 1;
Start page: 59;
Date: 2009;
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Keywords: Doxorubicin | Psychological Stress | Simvastatin | Diazepam | Cardiomyopathy

Critically ill patients as cancer patients usually suffer from stress, which is known to be implicated in the deterioration of their condition and the progression of other various disorders. Doxorubicin (DOX) is a highly effective antitumor, however its usefulness is limited due to the risk of developing cardiomyopathy. The present study was undertaken to investigate the role of psychological stress in enhancement of DOX cardiotoxicity, and the possible cardioprotective effect of simvastatin (SIM) and diazepam (DIZ) against such toxicity. DOX was administered to rats in 6 equal injections over a period of 2 weeks (cumulative dose, 15 mg/kg). Rats were exposed to stress-induced box paradigm 3 times during the period of DOX treatment (cumulative 30 volts for 3 h). Protection from stress-enhancement of DOX oxidative cardiac injury was assessed by administration of either (1)SIM(cumulative dose, 60 mg /kg) in 12 equal oral doses over a period of 4 weeks (2 weeks before and 2 weeks concurrent with DOX);or (2)SIM+ DIZ (0.1 mg /kg, i.p.) prior to each stress exposure. DOX treatment altered most of electrocardiograph parameters, and reduced body and heart weights. It also increased myocardial lipid peroxides and mortality%, and reduced myocardial glutathione (GSH), glutathione-S-transferase (GST), and DT-diaphorase activities. Psychological stress enhanced myocardial damage induced by DOX. Pretreatment with SIM or SIM+DIZ ameliorated cardiomyopathic changes-induced from stress-enhancement of DOX cardiotoxicity. These results demonstrate the role of psychological stress in enhancement of DOX cardiomyopathy and the qualitative differences in the protection provided by simvastatin and its combination with diazepam.

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