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.