الفهرس 
The heartOnly 14 pages are availabe for public view
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Abstract
Adrimycin is an anthracycline anti-neoplastic drug used in the treatment of a variety of human neoplasms. However, its toxicity on different organs especially the heart compromises its clinical effectiveness and is a major limiting factor for its clinical use in cancer chemotherapy (Saad et a/., 2000). The current study was designed to investigate the histological and histochemical changes that can be induced by ADR on the heart, liver and kidneys of the adult male albino rats using light microscopy and evaluate the presumed protective effect of captopril against ADR toxicity as well as the possible role of dose fractionation on reducing ADR- toxicity. Thirty six adult male albino rats were used in the present study. They were classified into 6 groups. Every group comprised 6 rats, 2 of them were used as control rats, and the remaining 4 were used as experimental rats. group (1) received a single dose of ADR, 15 mgkg while group (3) and group (5) received 3 mglkg of ADR weekly for 2 and 5 weeks respectively. Groups (2), (4) and (6) received the same dose of ADR as in groups (I), (3) and (5) respectively in addition to daily captopril, 10 mglkg. Each group was sacrified at the exact time; their organs were immediately extracted, washed by normal saline and fixed in 10% form01 saline. Sections were prepared for staining with Hematoxylin & Eosin, Massons’s trichrome and Periodic acid Schiff s stains. The stained sections were examined under the light microscopy to demonstrate the general histological structure, the connective tissue element, and the PAS+ve materials. In the present work, on giving a single dose of ADR (15mg/kg), significant histological and histochemical changes were observed in the myocardial, renal and hepatic tissues of group (1). The myocardial changes included focal myocardial necrosis, wide separation and thinning-out of the myocardial fibers with depletion of their glycogen stores, cellular infiltration, interstitial hemorrhage as well as congestion and dilation of the myocardial blood vessels. The ADR-induced hepatic changes included loss of the normal hepatic architecture, focal areas of necrosis, cytoplasmic vacuolation, pyknotic nuclei, congested, dilated portal and central veins, interstitial hemorrhage, cellular infiltration and depleted glycogen stores of the hepatocytes. Similarly, the ADR-induced renal changes involved glomerular congestion and sclerosis, partial obliteration of the capsular spaces, distortion of the parietal layer of the Bowman’s capsule, tubular dilatation, luminal casts, damaged endothelial lining, focal areas of tubular necrosis, loss of the apical brush borders of PCTs, interstitial cellular infiltration and depletion of the of the renal glycogen stores. In the current study, it was observed that fractionation of the total dose of ADR to be 3mg/kg, weekly for 5 weeks minimized its toxic effects on the heart, kidney and liver. This signifies a partial beneficial effect for dose fractionation in reducing ADR toxicity. Moreover, further improvement was noticed in group (5) which received fractionated small dose of ADR (3mg/kg, weekly for 2 weeks) emphasizing that ADR toxicity is dose-dependant. The myocardial fibers appeared less separated with little interstitial hemorrhage, mild interstitial cellular infiltration, mild increase in the interstitial and perivascular connective tissue together with improvement in the myocardial glycogen stores. Hepatic sections of this group showed preserved hepatic architecture, apparently normal central and portal veins, less cellular infiltration, many normal hepatocytes with improved glycogen stores. However, some hepatocytes in the peripheral zone appeared degenerated with mild increase in the perivascular connective tissue. Similarly, the renal sections of these rats showed less congested glomeruli with preserved capsular spaces, the PCTs appeared less dilated with preserved endothelial lining. There was also an improvement in the glomerular and tubular glycogen stores. On the other hand, the concomitant administration of captopril was found to attenuate the ADR-induced histological and histochemical changes in groups (2). More favouable results were seen in group (4) which received fractionated dose of ADR with captopril. The most promising results were seen in group (6), which received the smallest fractionated dose of ADR in addition to captopril. The myocardial sections of this group revealed apparently normal and adjacent myocardial fibers with normal vascular walls. The hepatic sections showed preserved hepatic architecture, apparently normal hepatocytes and central veins with re-establishment of the normal glycogen stores. The renal sections showed apparently intact renal glomeruli, intact endothelial lining of the renal tubules with preserved brush borders of many PCTs, scanty connective tissue and establishment of the renal glycogen stores. These fmdings suggest a possible partial protective role for captopril against ADR-induced toxicities.