الفهرس 
DEDICATION
AnatomyOnly 14 pages are availabe for public view
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Abstract
Cisplatin (CP) is a widely used DNA-alkylating antineoplastic drug. It is a very effective treatment either alone or as a member of multidrug regimens for many prevalent malignancies. Despite of the effectiveness of the treatment, patients suffer from prolonged and sometimes permanent problems from its toxicity. The present aim of all multi-agent chemotherapeutic protocols is to achieve a balance between highest care results and the least side effects. Different natural compounds have been recently investigated as potential protective agents against Cisplatin induced toxicity. Diosmin is a well-known flavonoid having a broad spectrum of biological activities, including antioxidant, modulator of capillary permeability and anti-carcinogeni widely used in medicine. Diosmin formulations are used for the treatment of chronic venous insufficiency, hemorrhoids, venous ulcers and the prevention of postoperative thromboembolism. Up to our knowledge, our work is the first work investigate the effect of Cisplatin in the structure and function of normal prostate and seminal vesicle. Accordingly, we aim in our study, to protect accessory sexual glands from any cytotoxic effect of Cisplatin that cause damage to these glands and alter their function by the use of Diosmin. Forty adult male albino rats were used in this study. They were divided into four equal groups. group I: Control , group II: Cisplatin treated group, rats were injected i.p. with a dose of 7.5 mg/kg Cisplatin at 5th and 12th day, group III: Diosmin (DS) administrated group, rats were given DS once daily at a dose of 100 mg/kg and group IV: Diosmin co-administered group, rats were treated orally with Diosmin at a dose of 100 mg/kg daily for 15 days during which they were injected with Cisplatin i.p at the same protocol of administration. After the period of experiment, Blood samples were collected for assessment of biochemical markers: Total antioxidant capacity (TAC), Malondialdehyde level (MDA),Prostate-Specific Antigen (PSA) and male hormonal assay. Then the animals were sacrificed and prostate and seminal vesicles were dissected out and processed for light, electron microscopic examination and immunohistochemical study. Testis and associated appendages were homogenized for obtaining seminal plasma for the measurement Zinc, Fructos, TAC and MDA. The epididymis from both testes were extracted for semen analysis. The results of this study revealed that Cisplatin induced toxic changes in both glands in the form of extensive thinning of the lining epithelium, destruction of epithelial cells and their desquamation in the lumen were observed, discontinuous basement membrane, collagen fibers deposition and fibrosis. Also caused cellular involution, in the form of reduction of rough endoplasmic reticulum, disappearance of secretory granules and abnormal mitochondria. Increase expression of Caspase-3 due to marked apoptosis, decrease Ki-67 and Cd44 expression. TAC, tissue homogenate fructose and zinc was reduced while MDA increased significally, tissue homogenate fructose and zinc All semen parameters were reduced. Administration of Diosmin resulted in great improvement of the glands’ structure and function being comparable to the control group.