الفهرس 
ContentsOnly 14 pages are availabe for public view
 |  | from | 164 |  |  |
| | | from | 164 | | |
Abstract
Testicular damage is one of the most hazardous effects of chemotherapy as it’s associated with oligozoospermia or azoospermia. Busulfan (BU) is an alkane sulfonate and is currently used as an anticancer drug. It causes several adverse effects including reproductive toxicity in humans. Antioxidants may protect the cells in testis against the toxic effects of the chemotherapeutic drugs. Melatonin (Mel) and Zinc oxide nanoparticles (ZnO NPs) are well-known antioxidants and have anti-apoptotic properties against toxicity of chemotherapeutic drugs. This study evaluated the potential effects of Mel or ZnO NPs in the treatment of azoospermia induced by BU in a mouse model. In this study thirty male albino mice were divided into 6 groups of 5 animals each: Control (oral 0.9% saline daily for 75 days); Mel (20 mg/kg/day orally for 30 days); ZnO NPs (5 mg/kg/day i.p. for 30 days); BU (single i.p. injection of 40 mg/kg and then left for 45 days); BU + Mel (single 40 mg/kg dose of BU and left for 45 days followed by 20 mg/kg/day Mel for 30 days); BU + ZnO NPs (single dose of 40 mg/kg of BU and left for 45 days, then 5 mg/kg/day ZnO NPs for 30 days). At the end of the experiment, both testes were weighed and prepared for histopathology, Masson trichrome staining, semithin sections were stained with toluidine blue , ultrastructural investigations immunohistochemistry, RT-PCR, and Western blot. Semen was obtained for hormonal and antioxidant analysis. Blood samples were collected to measure Testosterone (T), Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), glutathione peroxidase (GSH), malondialdehyde (MDA), and hydrogen peroxide (H2O2). Mel or ZnO NPs administered to BU-treated mice resulted in significant increases in sperm motility, sperm count, serum antioxidant enzymes activities, and serum T and FSH levels, and there was significant decrease in sperm abnormalities compared to the BU-treated mice. Also, Mel or ZnO NPs increased anti-apoptotic marker Bcl2, decreased apoptotic markers caspase-3 and Bax, and improved the histopathological alterations in testes. Ultrastructural observations showed that BU caused apoptotic chromatin condensation, abnormalities of Sertoli cells, spermatogonia, spermatocytes, round and elongated spermatids. Thick and irregular basal lamina, abnormal Leydig cells were also noticed. However, Mel or ZnO NPs supplementation ameliorated testicular alterations caused by BU.