| Abstract: |
The present work was undertaken to: 1) examine the cardiotoxic effect of doxorubicin either individually or in combination with TNFα inducer (LPS); 2) elucidate the protective effect of an antioxidant or a TNF inhibitor on experimentally DOX-induced cardiomyopathy. Such approaches may prove that this type of induced cardiomyopathy may be due to TNF induction in addition to the oxidative stress.The effect of doxorubicin, TNF inducer (LPS), antioxidant (taurine) and TNF inhibitor (rolipram) were studied on some biochemical parameters including:1- In serum : heart enzymes (CK-MB and LDH), TNF , free fatty acids and albumin.2- In plasma : NO, lipogram pattern (TC, TG, HDL-C) and susceptibility of non HDL-C to oxidation.3- In left ventricular tissue: oxidative stress markers (superoxide anion, lipid peroxides, SOD, CAT and total and nonprotein bound thiol) and calcium.Representative samples of rat left ventricle were processed for histopathological examination using electron microscope to configurate intracellular organelles changes and apoptosis and explore their possible correlations with the biochemical parameters.Experimental design:Adult male albino rats were randomly allocated into a control group and six treated groups, each of them was subdivided into 3 subgroups. They were treated with the following drugs for 2,4 and 6 weeks, respectively:Control group: Rats received 0.5 ml saline intraperitoneally.Group I: Rats treated with doxorubicin (2mg/kg/week, IP)Group II: Rats treated with doxorubicin and taurine (1gm/ kg/day, only 10 days pretreatment and during treatment period)Group III: Rats treated with doxorubicin and rolipram (3 mg/kg, IP. pretreatment and every 2 weeks during treatment).Group IV: Rats treated with doxorubicin and lipopolysaccharide (1mg/kg, IP.18 hrs before sampling).Group V: Rats treated with doxorubicin, lipopolysaccharide and taurine (using the previously mentioned doses and routes of administration).Group VI: Rats treated with doxorubicin, lipopolysaccharide and rolipram (using the dose regimens as mentioned before).<
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