الفهرس 
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Abstract
Duloxetine is the most recent dual reutake inhibitor of serotonin and norepinephrine that can produce dry mouth when used in the treatment of major depressive disorder. To investigate the effect Duloxetine(Cymbalta) on submandibular salivary glands of the rats, fifty adult male albino rats weighing 200-225 gram body weight were used in this investigation.The animals were divided as follows:-Group1 animals consisted of 20 rats and served as controls.-group 2animals consisted of 30 animals, they were subjected to daily oral dose of Duloxetine in a dose of 10mg/kg body weight dissolved in distilled water using curved metallic oropharyngeal tube for 3 months.At the end of the experiment half of the animals of both groups (gr.1.1,2.1) were sacrificed by cervical dislocation,their submandibular salivary glands were dissected out.those of right side were fixed in 10%neutral buffered formalin,processed ,embedded in paraffin,sectioned and stained with:1-Hematoxylin and eosin for histological examination.2-Immunoperoxidase technique for immunohistochemical localization of cytokeratin 5,6 &18 using anticytokeratin monoclonal antibodies.The submandibular salivary glands of the left side were prepared for electron microscopic examination :• Small sized (13 mm) samples were taken from submandibular salivary glands of the left side of the animals of the different groups and prepared for transmission electron microscope examination.• Semithin sections (1-2 microns thick) were cut and stained wiyhtoludine blue to be examined with the light microscope for orientation and localization of the site to be examined by electron microscope.• Ultrathin sections (0.06 microns )were cut, mounted on copper grids and stained with saturated uranyl acetate followed with lead citrate to be examined with transmission electron microscope.• The rest of the animals of both groups (gr.1.2,2.2) were allowed a recovery period of 30 days. After which they were sacrificed and their submandibular salivary gland were excised and treated in the same way as groups 1.1&2.1.Results:A )Microscopic and submicroscopic results:• The histological examination of the submandibular salivary gland of group 2.1 showed variable degrees of degenerative changes. The secretory portion and ducts appeared atrophic, shrunken with apparent reduction in their number and size which was manifested as presence of empty spaces around them. The serous acinar cells were atrophic and showed variable degrees of cytoplasmic vacuolization ranging from moderate to extensive vacuolization which exerted pressure against the nuclei , which became pyknotic ,sometimes pushed against the plasma membrane of the cells. Most of mucous acinar cells appeared edematous and swollen.The striated ducts presented degenerative changes manifested as cytoplasmic vacuolization,apparent decrease in their size with marked shrinkage and sometimes massive destruction. Shortening of basal infolding of plasma membrane striated ducts. Dilated rough endoplasmic reticulum with presence of degenerated and ruptured mitochondria. The granular covulated tubules showed apparent decrease in their size , marked decrease in their eosinophilia and granular contents together with intracytoplasmic vacuolization. The excretory ducts showed thinning and atrophy of their epithelial lining with extremely wide lumen filled with stagnant secretions. The nuclei appeared shrunken with irregular nuclear membrane .The connective tissue septa were extremely widened and degenerated with a lot of markedly dilated blood vessels.The histological examination of submandibular salivary gland of animals with recovery period of 30 days (group 2.2) showed variable degrees of improvements in their histological structures. The secretory portions and ducts began to restore their structure but still vacuolization in the striated ducts was evident. The serous and mucous acinar cells showed little vacuolization. The granular convulated tubules still showed large vacuolization but they regain their granularity. The excretory ducts showed recovery of the atrophic lining . there was minimal regeneration of the connective tissue septa with moderate dilatation of blood vessels.At the ultrastructural level the secretory cells showed partial regeneration of their mitochondria. The nuclei showed relative pyknosis and irregularity . Rough endoplasmic reticulum was dilated in some areas and adundant in others. Large Golgi complex and secretory granules of normal electron densities in cells of serous acini were observed.The intercalated ducts showed degenerated mitochondria minimal vacuolization and slightly dilated rough endoplasmic reticulum.