الفهرس 
CyelosporineOnly 14 pages are availabe for public view
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Abstract
This work was done aiming firstly to study the changes which may occur in some organs ”liver, kidney, spleen and bone marrow” in the adult albino rats after administration of two immunosuppressive drugs ”cyclosporine A and azathioprine” and the reversible effects after stoppage of the drugs. Secondly, to study the teratogenic effects of these drugs on the off spring of albino rats and the changes in some of their organs ”liver, kidney and spleen”. Two hundred and thirty adult albino rats and off spring of both sexes were used in this study. Fifty adult albino rats and off spring were used as a control group and were divided into twenty adult control albino rats, ten pregnant female to give off spring and only twenty of their off spring were taken. In the experimental study, one hundred and eighty adult albino rats and off spring of both sexes were used and divided into two major groups. Group(1): Ninety adult albino rats and off spring of both sexes were used to study the effects of cyclosporine A at different periods, after 4 weeks, 6 weeks and after 3 weeks withdrawal of the drug and its teratogeinc effects. group (2): Ninety adult albino rats and off spring of both sexes were used to study the effects of azathioprine at different periods, after 4 weeks, 6 weeks and after 3 weeks withdrawal of the drug and its teratogenic effects. The specimens from ”liver” kidney, spleen and bone marrow” were taken. Each of them was divided into two parts, one part was fixed and subjected to light microscopic study using different stains: 1- Haematoxylin and eosin stain for routine histological examination. 2- Mallory’s trichrome stain for detection of the connective tissue. 3- Mc Donald’s modification of Lascano’s technique: to demonstrate Golgi apparatus. The other part of the specimens was fixed and prepared for transmission electron microscopic examination to study detailed cytological structures. Bone marrow specimens were prepared as semithin sections and stained with toluidine blue stain. The results of this work were summarized as follows: The liver: After administration of cyclosporine A for 4 weeks, sections in the liver showed dilated congested central vein with cytoplasmic vacuolation, degenerated mitochondria, dilated sER and indented nucleus with clumped chromatin. After 6 weeks, there were marked dilated congested central vein, loss of hepatic architecture, marked increased connective tissue, large 2ry lysosomes and fibrin strands. After 3 weeks withdrawal of the drug, regressive changes were seen as regain of hepatic architecture, absence of cytoplasmic vacuolation, the nucleus began to have normal shape but some degenerated mitochondria were found. Afier administration of azathioprine for 4 weeks, sections in the liver showed loss of hepatic architecture, increased connective tissue and loss of cell boundaries of hepatocytes. After 6 weeks, progressive changes were seen as degenerative nuclear changes, increased connective tissue, degenerated mitochondria, rough endoplasmic reticulum and Golgi apparatus. After 3 weeks withdrawal of the drug, regressive changes were found as regained of the cell boundaries and hepatic architecture could be seen. The nucleus in some hepatocytes regain their normal shape and also some mitochondria appeared with normal shape. The kidney: After administration of cyclosporine A for 4 weeks, sections in the kidney showed shrunken glomeruli, widening of Bowman’s space, degenerated mitochondria in the tubules and sub-endothelial deposits with loss of foot processes arrangement. After 6 weeks, marked glomerular and tubular degeneration, thickened glomerular basement membrane and indented nuclei with clumped chromatin were found. After 3 weeks withdrawal of the drug, regressive changes were found as the glomeruli and some tubules regain their shape, apparently normal shaped nuclei of the tubules but thick glomerular basement membrane and disturbed foot processes arrangement were still present. After administration of azathioprine for 4 weeks, sections in the kidney showed partial loss of the epithelial lining of its parietal layer of Bowman’s capsule, dilated tubules, long slender foot processes and swollen mitochondria. After 6 weeks, mild widening of the capsular space with peri-glomerular hemorrhage, marked increased connective tissue, loss of arrangement of foot processes were observed. After 3 weeks withdrawal of the drug, widening of the capsular space, degeneration of the epithelial lining of the tubules, mild increased connective tissue, indented nucleus of the tubules and subendothelial deposits were found. The spleen: After administration of cyclosporine A for 4 weeks, sections in the spleen showed apparent reduction in the size of the lymphoid follicles size, dilated congested splenic sinusoids, scanty cytoplasm and indented nucleus of the lymphocyte. After 6 weeks, faint coloration of lymphoid follicle, clumped chromatin of the lymphocytes. After 3 weeks withdrawal of the drugs regressive changes were noticed as the lymphoid follicles apparently regain their shape. A lymphocyte with clumped chromatin could be seen . After administration of azathioprine for 4 weeks, sections in the spleen showed reduction in the size of lymphoid follicle and degenerative changes in the lymphocytes. After 6 weeks, progressive changes were found as increased depletion of the lymphocytes, fragmented Golgi granules and indented nucleus with clumped chromatin of the lymphocyte. After 3 weeks witlzdrawal of the drug, regressive changes were noticed as the lymphoid follicles began to have their shape and coloration and indented nuclei but with normal amount of cytoplasm. The bone marrow: After administration of cyclosporine A for 4 weeks, sections in the bone marrow showed apparently normal cellular density was seen. After 6 weeks, apparently mild decreased cellular density. After 3 weeks withdrawal of the drug, apparent slight decrease in the cellular density could be observed. No cytological changes could be noticed and many hemopoietic stages were found. After administration of azathioprine for 4 weeks, sections in the bone marrow showed mild decrease in the cellular density. After 6 weeks, progressive decrease in the cellular density could be seen. After 3 weeks withdrawal of the drug, regressive changes were seen but apparently mild decrease in the cellular density was present. No cytological changes could be seen and many hemopoietic cells were found. Terutogenic effects of cyclosporine A: A significant decrease in length and weight of the full term rat with no external gross malformation were found. The liver showed dilated and congested hepatic sinusoids with disturbed hepatic architecture. The kidney showed widening of Bowman’s capsule with loss of epithelial lining of the tubules. The spleen showed dilated splenic sinusoids with ill- differentiated between red and white pulp. Terutogenic effects of azuth ioprine: Marked significant decreases in length and weight of the full term rat with no external gross malformation. The liver showed marked dilated congested central vein and hepatic sinusoids with loss of hepatic architecture and degenerative nuclear changes. The kidney showed small cortex with apparently less glomeruli. The spleen showed ill- defined capsule, red and white pulp. So, teratogenic effects of cyclosporine A and azathioprine were found to be more or less mild.