role of calcium channel blockers against cyclosporine-induced hepatorenal toxicity

The present work investigated the changes induced by cyclosporine on the liver and kidney and clarified the possible protective role of calcium channel blockers. Cyclosporine caused distortion of the liver parenchyma as well as severe congestion in the central vein. Also there was loss of cellular demarcation with indistinct cell boundaries. By the electron microscope the hepatocytes in the affected areas revealed depleted cytoplasm, and mitochondria with partial loss of their cristae. The rough endoplasmic reticiulum showed slight dilatation and fragmentation. The calcium channel blocker [amlodipine] enhanced the preservation of the control pattern in most hepatocytes apart from few hepatocytes showing areas of depletion, irregular arrangement of endoplasmic reticiulum, few glycogen granules and smaller nuclei. Regarding the kidney, cyclosporine caused different modalities of degeneration in the capillary tuft of the renal corpuscles. Both the proximal and distal tubules showed widening of their lumen, distortion of their cellular pattern As for the cells of the proximal tubules, they showed disrupted brush border, loss of the basal striations with irregular nuclei. Some tubules also contained areas of exudation. Extravasation of red blood corpuscles was evident. The podocytes, by the electron microscope, had vacuolated cytoplasm and irregular nuclei. The mesangial cells had paler matrix than the control group. Peritubular fibrosis was observed. The cytoplasm of the cells of the proximal tubules contained large lysosomes and autophagic vacuoles

Effects of cyclophosphamide administration on the lung of albino rat and protective role of antioxidants

The present work was designed to study the effects of cyclophosphamide on the albino rat lung, and to demonstrate the possible protective role of the antioxidants. The results revealed that administration of cyclophosphamide [20 mg/ kg b.w.] for one week caused thickening of the alveolar wall with partial detachment and degeneration of type II pneumocytes. Signs of congestion and fibrosis were also detected. Administration of cyclophosphamide [20 mg/kg b.w.] for two weeks caused pleomorphic cellular proliferation and obliteration of the alveolar lumen. Degenerative changes were noticed in both type I and type II pneumocytes. Type I pneumocytes manifested altered nuclear chromatin pattern and vacuolated cytoplasm. Type II pneumocytes showed detached microvilli, irregular cell membrane, pyknotic nucleus and multiple interconnected empty lamellar bodies. Signs of congestion and cellular infiltration by plasma cells, mast cells and neutrophils were noticed with accumulation of thick elongated collagen bundles in the alveolar wall. Administration of the antioxidants [0.1 ml of Antox], minimized the toxic effects of cyclophosphamide and even allowed regeneration of the alveolar wall. Regarding the alveolar pneumocytes, binducleated type II pneumocytes were noticed. Furthermore many pneumocytes acquired features intermediate between type I and type II in an attempt to restore the alveolar wall. Fibrosis and congestion were minimized

Effects of surgical castration on the lymphoid tissue of the thymus of old mice compared to the effects of chemical castration induced by flutamide

This study was performed to illustrate and compare the effects of surgical castration and chemical castration induced by the antiandrogen flutamide [0.5 mg/g body weight] on the regeneration of the thymus of old mice. One month following surgical castration, the thymus was reconstituted into cortex and medulla. The cortex contained mainly small lymphocytes and large lymphocytes with few epithelial cells, while in the medulla, the epithelial cells were more prominent. Ultrastructurally, numerous lymphocytes contained mitochondria, dense bodies, ribosomes and membrane bound granules, in addition to protruding swellings adjacent to cell membrane containing whorly material. Few lythphocytes showed cytoplasmic continuity. On comparing the group that received flutamide for one month with tIme group surgically castrated for the same period, it was evident that chemical castration produced significant increase in the cortical samll lymphocytes and epithelial cells. Furthermore, the medulla exhibited significant increase in its lymphocytic content, but still the epithelial cells were the major constituting cells, their cytoplasm contained abundant mitochondria, microtubules, ribosomes and rough endoplasmic reticulum. On comparing the group that received flutamide for two months with the group surgically castrated for the same period, it was evident that chemical castration allowed more pronounced proliferation and lamination of the rough endoplasmic reticulum of the cortical lymphocytes. Furthermore, it resumed the mitotic activity. Regarding the medulla, chemical castration, allowed significant increase in the medullary lymphocytes, more evident proliferation in the rough endoplasmic reticulum and resumed the mitotic activity. The present study further clarified that the extent of regeneration was dependent on the duration of gonadal deprivation. Therefore, prolonged chemical castration is more effective in regeneration of the thymus gland in old mice