Abstract
The aim of the present investigation was to study the toxic influences of taxol (TXL) on the testes of rats and the protective impact of melatonin (MLT) against such effects. Rats were classified into control, sham, TXL, MLT, and MLT+TXL-treated groups. Histological and ultrastructural changes were observed in testicular tissues of TXL-intoxicated rats including thickening of tunica albuginea and degenerative alterations in spermatogenic, Sertoli, and Leydig cells. A significant increase (P≤0.05) was found in the thickness of tunica albuginea and numbers of tubules without sperm, apoptotic germinal epithelia, and apoptotic Leydig cells, whereas the diameter of tubules and height of germinal epithelia displayed a significant decrease (P≤0.05) compared with the control, sham, and MLT-treated groups. Immunohistochemically, a marked decrease (P≤0.05) in Bcl-2 immunoreactivity and significant elevation (P≤0.05) in P53 and caspase-3 immunoreactivities were recorded. Co-treatment of MLT and TXL modulated such histological, histomorphometrical, and ultrastructural changes induced by TXL. Also, MLT had a protective effect against testicular apoptosis induced by TXL, as shown by the elevated expression of Bcl-2 and decreased expression of P53 and caspase-3. In conclusion, the current investigation proved that MLT had a protective role against TXL-induced testicular cytotoxicity, which may be a result of inhibition of testicular apoptosis.
Highlights
Cancer is a serious public health problem worldwide and a leading cause of death, claiming the lives of nearly 18.1 million individuals each year [1]
B-cell lymphoma 2 (Bcl-2), P53, and Cas3 immunoreactivities were assessed by estimating the area percentage of the positive immunostained cells in relation to the total number of cells examined at Â200 magnification in 5 selected fields with a standard measuring frame of 11,434.9 mm2 using the computed image analysis system at Department of Oral and Dental Pathology, Faculty of Dental Medicine for Girls, Al-Azhar University
Histological results Testes of control rats (Figure 1A and B) and of sham rats (Figure 1C and D) showed normal histological structure of active mature functioning seminiferous tubules associated with complete spermatogenic series and separated by regular interstitial tissues, having distinct Leydig cells and blood vessels
Summary
Cancer is a serious public health problem worldwide and a leading cause of death, claiming the lives of nearly 18.1 million individuals each year [1]. As an efficient chemotherapeutic agent and mitotic inhibitor, taxol (TXL), the first authorized paclitaxel formulation in 1992, is arguably one of the most effective anti-cancer drugs of all times, some other formulations are available. TXL, a plant alkaloid and an antimicrotubule agent, promotes tubulin polymerization and prevents microtubule depolymerization, which is crucial for cell division. Other mechanisms such as intracellular signaling alteration and organelle transportation have a vital role in the anticancer properties of TXL [5]. TXL does not have a targeted action like other chemotherapeutic drugs, and it causes cell death, leading to severe side effects that reduce its efficiency [6]
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