MELATONIN ATTENUATES TESTICULAR DYSFUNCTION AND SPERM DAMAGE INDUCED BY CHEMOTHERAPY REGIMEN BASED ON BLEOMYCIN, ETOPOSIDE, AND CISPLATIN (BEP): AN EXPERIMENTAL STUDY

نویسندگان

چکیده

To determine the protective effects of exogenous melatonin following exposure to Bleomycin, Etoposide, and Cisplatin (BEP) chemotherapy on sperm parameters DNA integrity, testes nitro-oxidative status, as well histopathological, inflammatory, apoptotic alternations in rats testes. Adult male Wistar were randomly segregated into six groups (n=10/group). Groups 1, 3, 4 intraperitoneally injected with vehicle, 10 20 mg/kg melatonin, respectively. Other received one cycle 21 days 0.5 therapeutically relevant dose levels BEP (0.75 7.5 Etoposide 1.5 Cisplatin) or without melatonin. Sperm parameters, including count, motility, viability, morphology, chromatin integrity using aniline blue (AB), toluidine blue(TB), Chromomycin A3 (CMA3) analyzed. Besides, testosterone level, histopathology stereology testes, malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC) testes; expression apoptosis-related genes such Bcl2, Bax, Caspase-3, p53, TNF-α (Real-time PCR Immunohistochemistry) assessed. According our results, quantitative analysis testes' stereological procedures, QRT-PCR examination, immunohistochemical (IHC) staining revealed that reversed BEP-induced compromised spermatogenesis (P<.05). In this regard, rectified disturbance morphology. Additionally, co-administration could restore alteration methylation fragmentation compared group. Moreover, enhanced status testis by elevating TAC ameliorating MDA NO levels. More interestingly, therapy prevented apoptosis attenuating apoptosis-associated Bcl-2, p53. (P<.01). continuum, regimen decreased significantly population p53 positive cells while augmented Bcl-2 protein spermatogenic line comparison Together, adversely affects testicular functions leading compromise integrity. Although not completely, contributes preserving from BEP-evoked damages via preventing stress, inflammation, apoptosis. Since experimental design mostly resembles protocol used humans, these findings may have widespread clinical implications for minimizing chemotherapy-related sub/infertility shortening fertility recovery time patients receiving regimen.

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ژورنال

عنوان ژورنال: Fertility and Sterility

سال: 2021

ISSN: ['0015-0282', '1556-5653']

DOI: https://doi.org/10.1016/j.fertnstert.2021.07.916