الفهرس 
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Abstract
Doxorubicin (Dox) is a potent antineoplastic agent extensively used in the treatment of several malignancies. Nevertheless, its clinical application carries the risk of serious non-target tissues toxicities, in particular cardiomyopathy, which manifests as life-threatening congestive heart failure. Consequently, there is a much great interest to search for natural compounds with cardioprotective properties to decrease this cardiotoxic effect.
The main objective of this study was: 1- To evaluate the antihyperlipidemic and anti-atherogenic effect of date palm fruit extract against alterations in lipid metabolism induced by Dox. 2- To assess antioxidative activity of date palm fruit extract on Dox associated with oxidative stress. 3- To elucidate role of date palm fruit extract in the prevention of alteration in biomarkers of myocardial damage (creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH) and troponin-I) induced by Dox. 4- To monitor the ability of date palm fruit extract to ameliorate the changes in ECG patterns of Dox intoxicated rats.5- To examine the putative preventive effect achieved by date palm fruit extract on histopathological abnormalities induced by Dox.
Forty rats weighting (120-140 g) were equally divided into equal four groups:
group I (control group): Healthy rats received a vehicle.
group II (date group): Healthy rats received date palm fruit extract (4ml/kg b.w. / day orally) for thirty days (Vayalil, 2002).
group III (Dox group): Healthy rats received a vehicle for thirty days and then received a single dose of Dox (15 mg/kg b.w., i.p.) (Chabner et al., 2001).
group IV (protected group): Healthy rats received date palm fruit extract (4ml/kg b.w. / day orally) for thirty days and then received a single dose of Dox (15 mg/kg b.w., i.p.).
At the end of the experimental period and after 24 hours of Dox injection, animals were kept in metabolic individual cages for collection of 24 hours urine samples for estimation of urinary 8-OHdG. Forty eight hours after Dox injection, rats were anesthetized using diethyl ether by inhalation and ECG was recorded for 1 min before blood sampling.
After blood sampling, rats were decapitated and heart tissues were divided into two parts; the first part was prepared for histopathological examination by routine light microscopic methods; and the second part was prepared for biochemical analysis.
The following parameters were estimated:
1- Serum lipid profile (serum total cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C)).
2- Atherogenic indices (atherogenic coefficient (AC), cardiac risk ratio (CRR) and atherogenic index (AI)).
3- Oxidant and antioxidant profile (cardiac glutathione peroxidase, cardiac superoxide dismutase, cardiac malondialdehyde and urinary 8-OHdG).
4- Cardiac profile (CK-MB, LDH and troponin-I).
5- ECG pattern (heart rate, PR duration, corrected QT interval (QTc), and ST height).
Histopathological examinations were done for heart tissue of all studied groups.
The results obtained were summarized as follow:
The mean values of total cholesterol ,triglycerides ,LDL , AC, CRR , AI ,CK-MB ,LDH , troponin-I , urinary 8-OHdG , PR duration and ST height in Dox group were significantly increased compared to control group . In contrast, the mean values of HDL-C, cardiac SOD, heart rate and QTc in Dox group were significantly decreased compared to control group while cardiac MDA and GPx were insignificantly changed. These results were confirmed with histopathological results.
In protected group, the mean values of total cholesterol, LDL-C, AC, CRR, urinary 8-OHdG, CK-MB, LDH, troponin-I, PR duration and ST height were significantly decreased compared to Dox group. While those of cardiac SOD and heart rate were significantly increased. In contrast, the mean values of serum triglycerides, HDL-C, AI, cardiac MDA, cardiac GPx and QTc were insignificantly changed in protected group as compared to Dox group. These results were confirmed with histopathological results.