title: The effect of melatonin on procarbazine induced testicular toxicity on rats.
abstract: Procarbazine (P) is an effective chemotherapeutic drug especially used in lymphoma treatment; however testicular toxicity is a limiting factor. Various ways of treatment were tried to preserve testicular function including hormonal treatment, antioxidant treatment, and sperm cryopreservation but resulted with low rates of satisfaction. Procarbazine is a well known agent causing sterility even in the first doses of chemotherapy. Antioxidants such as N acetylcysteine and ascorbate have been used for protective purposes and were very successful. Melatonin (M) is another powerful antioxidant and we aimed to use M for the protection of P induced testicular toxicity in this study. Procarbazine was given peroral by gavage once a week at a dose of 62.5 mg/kg/week for 4 weeks (total dose: 250 mg/kg) (P group) and in procarbazine + melatonin (PM) group, 10 mg/kg melatonin was intraperitoneally administered daily for five days a week for 4 weeks (total 20 days). The experiment ended at day 90. In the P and PM groups the testicle width, length, and weight, sperm A and sperm AB properties (Sperm A: sperms straight line progressive, Sperm B: sperms straight slow progressive, Sperm AB: Sperm A + Sperm B), spermatogonia, Sertoli cells, seminiferous tubule, and germinative layer thickness were lowered as compared with the control group. However, there were no significant differences between the P and PM groups in regard to these parameters. Melatonin preserved Sertoli cell and spermatogonia function. The testosterone and follicle-stimulating hormone (FSH) levels were also preserved. Melatonin significantly decreased malondialdehyde (MDA) levels and preserved the antioxidant enzyme levels such as glutathione peroxidase (GPx) and nitrite nitrate (NO2-/NO3-). Melatonin may protect testicular functions in P treated patients and is open to consideration during chemotherapy since it appears to be without any side effects.
authors.affiliation: Department of Urology .
authors.forename: Bilal Fırat
authors.initials: BF
authors.lastname: Alp
authors.forename: Vural
authors.initials: V
authors.lastname: Kesik
authors.forename: Ercan
authors.initials: E
authors.lastname: Malkoç
authors.forename: Nuri
authors.initials: N
authors.lastname: Yiğit
authors.forename: Mehmet
authors.initials: M
authors.lastname: Saldır
authors.forename: Oğuzhan
authors.initials: O
authors.lastname: Babacan
authors.forename: Emin Özgür
authors.initials: EÖ
authors.lastname: Akgül
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Poyrazoglu
authors.forename: Nadir
authors.initials: N
authors.lastname: Korkmazer
authors.forename: Mustafa
authors.initials: M
authors.lastname: Gulgun
authors.forename: Onur
authors.initials: O
authors.lastname: Erdem
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D000975:Antioxidants / Q000494:pharmacology*; D019610:Cytoprotection; D004195:Disease Models, Animal; D005640:Follicle Stimulating Hormone / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008550:Melatonin / Q000494:pharmacology*; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D011344:Procarbazine; D017208:Rats, Wistar; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000473:pathology; D013733:Testicular Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D009566:Nitrates; D009573:Nitrites; D011344:Procarbazine; D013739:Testosterone; D008315:Malondialdehyde; D005640:Follicle Stimulating Hormone; D005979:Glutathione Peroxidase; D008550:Melatonin
keywords: Antioxidant; melatonin; procarbazine; sterility; testicular toxicity