الفهرس 
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Abstract
Introduction: The great development in nanotechnology has led to the wide use of nanoparticles. Titanium dioxide nanoparticles (TNPs) are among the top nanoparticles used all over the world. With their different shapes, sizes, and crystalline forms, TNPs have been used in many products such as plastic, paper, ink, cosmetics, food additives in candies and sweets, and as a whitening pigment in skimmed milk. In addition, TNPs can also be used in the water purification and toothpaste industries. In the medical field, they can be utilized in dental, orthopedic implantations and bladder stents. Coenzyme Q10 (CoQ10) is a lipid-soluble vitamin, naturally found in many types of food such as fish, meat, broccoli, and orange. It is a natural mitochondrial component as it enhances the synthesis of ATP by acting as electron carrier in mitochondrial electron transport chain. It can inhibit peroxidation, so it plays an important role in cell membrane stabilization and mitochondrial protection. It acts as an antioxidant, scavenging free radicals and also it has anti-apoptotic effects. Aim of the work: This work was performed to study the effect of titanium dioxide nanoparticles on the histological structure of the ventral lobe of the prostate in adult albino rat and to evaluate the protective role of coenzyme Q10 using different histological and immunohistochemical methods. Materials and methods: The current work was carried out on 40 adult male albino rats. They were divided into 4 main groups: 1- group I (Control group): included 10 rats that were further subdivided into 3 subgroups: Subgroup IA: included 4 rats that did not receive any treatment. - Subgroup IB: included 3 rats that received 1ml of 1% gum acacia solution once daily through a gastric tube for 4 weeks. - Subgroup IC: included 3 rats that received 1ml of 5% gum acacia solution once daily through a gastric tube for 4 weeks. 2- group II (CoQ10 group): included 10 rats that were given CoQ10 at a dose of 20 mg/kg dissolved in 1% gum acacia solution through a gastric tube once daily for 4 weeks. 3- group III (TNPs group): included 10 rats that were given TNPs at dose of 600 mg/Kg suspended in 5% gum acacia solution through a gastric tube once daily for 4 weeks. 4- group IV (TNPs/ CoQ10 group): included 10 rats that were given CoQ10 alone for one week, then they received it with TNPs at the same time for 4 weeks. Both drugs were administered with the same doses and the same protocol as groups II and III. At the end of the experimental period and 24 hours after the last dose, the rats of all studied groups were anesthetized with intraperitoneal injection of sodium pentobarbital (50 mg/Kg). The specimens of the ventral prostate were carefully dissected from the prostate-urethra-bladder complex and processed for light and electron microscopic examination. For light microscopic study, paraffin sections were stained with H&E and Mallory’s trichrome stains. Immunohistochemical study was done by using α-SMA antibodies. Ultrathin sections were stained with uranyl acetate and lead citrate for electron microscopic examination. In addition, Image J software was used for image analysis of the mean height of prostatic epithelium and the mean area percentage of collagen fibers stained with Mallory’s trichrome and α-SMA positive immunoreaction. Results: characterization of TNPs with TEM revealed that the individual particles were electron dense, spherical in shape with an average diameter of 25 nm and formed aggregates of different sizes. The results of the current study were recorded and could be summarized as the following: 1- group I (Control group) and group II (CoQ10 group): The H&E-stained sections of both groups showed the normal known structure of the ventral lobe of prostatic gland. The slightly packed prostatic acini had variable sizes and shapes and separated by minimal amount of stroma. Most of the acini lumina contained variable amounts of pale stained acidophilic secretion. The acini were lined by a single layer of cuboidal or columnar epithelial cells with basophilic cytoplasm and basal rounded vesicular nuclei with prominent nucleoli with few number of papillary projections. The acini were surrounded by a single continuous layer of smooth muscle cells. Mallory’s trichrome-stained sections of both groups revealed minimal amount of collagen fibers in the stroma between the prostatic acini. In addition, immunohistochemical examination revealed a thin layer of positive α-SMA cytoplasmic immunoreaction in smooth muscle cells around the prostatic acini. Electron microscopic examination of these groups confirmed the light microscopic results. The acini were lined by tall columnar cells with indistinct boundaries and rest on basement membrane. They were surrounded by a few layers of spindle-shaped smooth muscle cells and fibroblasts. The columnar acinar cells showed basal and oval euchromatic nuclei with prominent nucleoli, slightly dilated parallel RER cisternae, dispersed mitochondria in between them and apical membrane-bound secretory granules. Apical cell membranes showed regularly organized microvilli. Basal cells were flattened, laying parallel to and in contact with the basement membrane; their apical borders did not reach the lumen. They contained oval nuclei occupying most of the cytoplasm. 2- group III (TNPs group): The H&E-stained sections of this group revealed some focal histological changes compared to the control group. Multiple prostatic acini appeared packed and crowded with different sizes and shapes and some other acini were widely separated with obviously increased deposition of the connective tissue stroma containing multiple congested blood vessels and perivascular cellular infiltration with precipitation of homogenous acidophilic material between the acini. The peri-acinar smooth muscle cell layer thickened and completely encircled the acini. Most of the acini were lined by columnar cells with apparent increase in their height and forming papillary projections that protruded into the lumina of some acini and other focal areas showed stratified disorganized cells. Most of the cells were swollen with vacuolated cytoplasm and some showed normally appeared nuclei, while other sparse cells showed some nuclear changes such as darkly stained nuclei, hollow circular like nuclei, fragmented nuclei or complete nuclear lysis. Statistical results of data displayed a highly significant increase in the mean height of prostatic epithelium when compared with the control group. Mallory’s trichrome-stained sections of this group revealed a highly significant increase of mean area percentage of the collagen fibers in the stroma between the prostatic acini. In addition, the immunohistochemical examination revealed a highly significant increase in the mean area percentage of the positive α-SMA cytoplasmic immunoreaction compared to control group. Electron microscopic examination of this group confirmed the light microscopic results, most of the acini were lined with a single layer of tightly packed, tall columnar cells, and other areas were lined with two to three columnar cell layers. Moreover, the acini were surrounded by multiple layers of smooth muscle cells. Most of the acinar cells had indented nuclei with prominent nucleoli, markedly dilated RER cisternae, focal areas of cytoplasmic rarefaction as well as cytoplasmic vacuoles. Electron-dense particles, which may be TNPs, appeared in the cytoplasm and vacuoles and electron dense heterogeneous secondary lysosomes. Some cells showed few or even depleted apical secretory granules. The overlying apical microvilli appeared disorganized and fragmented. In some acini, very few cells showed loss of the apical microvilli, rupture of the cell membrane and release of cytoplasmic content into the lumen. The cytoplasm appeared rarefied and the nuclei were shrunken and condensed with peripheralization of the chromatin. The basal cells appeared swollen with electron-lucent cytoplasm, no visible organelles and large indented nuclei occupying the majority of the cytoplasm with margination of clumped chromatin. 3- group IV (TNPs/ CoQ10 group): The H&E-stained sections of this group showed few focal changes, few acini were focally lined by more than one cell layer with few papillary projections. Few cells had vacuolated cytoplasm and others had dark nuclei and homogenous acidophilic cytoplasm. However, most sections showed normal histological structure of the ventral lobe of the rat prostate gland more or less similar to those of the control group. Statistical results displayed a highly significant decrease in the mean height of prostatic epithelium when compared with the TNPs group. Mallory’s trichrome-stained sections of this group revealed a highly significant decrease of mean area percentage of the collagen fibers in the stroma between the prostatic acini. In addition, the immunohistochemical examination revealed a highly significant decrease in the mean area percentage of the positive α-SMA cytoplasmic immunoreaction compared to TNPs group. Electron microscopic examination of this group revealed that most of the acini were lined by a single layer of columnar cells with basal euchromatic rounded to oval nuclei with prominent nucleoli, slightly dilated parallel RER cisternae and apical membrane-bound secretory granules and some normal dispersed mitochondria. Microvilli were found in a regular pattern on the apical cell membranes. However, focal changes were observed in a few cells that revealed some cytoplasmic vacuoles contained cellular debris.