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: Bilal Fırat Alp, Vural Kesik, Ercan Malkoç, Nuri Yiğit, Mehmet Saldır, Oğuzhan Babacan, Emin Özgür Akgül, Yavuz Poyrazoglu, Nadir Korkmazer, Mustafa Gulgun, Onur Erdem
• Journal: Systems biology in reproductive medicine (Syst Biol Reprod Med) Vol. 60 Issue 6 Pg. 323-8 (Dec 2014) ISSN: 1939-6376 [Electronic] England
• PMID: 25140409 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Antioxidants
• Nitrates
• Nitrites
• Procarbazine
• Testosterone
• Malondialdehyde
• Follicle Stimulating Hormone
• Glutathione Peroxidase
• Melatonin

Topics

• Animals
• Antineoplastic Agents
• Antioxidants (pharmacology)
• Cytoprotection
• Disease Models, Animal
• Follicle Stimulating Hormone (blood)
• Glutathione Peroxidase (blood)
• Male
• Malondialdehyde (blood)
• Melatonin (pharmacology)
• Nitrates (blood)
• Nitrites (blood)
• Procarbazine
• Rats, Wistar
• Sertoli Cells (drug effects, metabolism, pathology)
• Sperm Motility (drug effects)
• Spermatozoa (drug effects, pathology)
• Testicular Diseases (blood, chemically induced, pathology, prevention & control)
• Testis (drug effects, metabolism, pathology)
• Testosterone (blood)