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.

Effects of saturated palmitic acid and omega-3 polyunsaturated fatty acids on Sertoli cell apoptosis

“…The specimens of the testes that were used for histopathological analysis were collected by a method similar to that described by Alp et al (Alp et al 2014). Briefly, the testes were fixed in 4% paraformaldehyde.…”

Evaluations of cytotoxicity of Smilax myosotiflora and its effects on sexual hormone levels and testicular histology in male rats

“…Adverse effects of any deleterious compounds on spermatogenesis are manifested by five mechanisms, including alteration in the level of the reproductive hormones such as FSH, LH and testosterone, increase in capillary permeability of testicular blood vessels which result in generalized edema and testicular disruption [29], toxicity to Sertoli cell resulting in sloughing and reducing spermiogenesis, decreased spermatogenesis in the absence of apparent Sertoli cell toxicity and chromosomal aberrations and unscheduled DNA synthesis, sometimes accompanied by cytotoxicity [30] . In our investigations, there was no evidence of disruption in spermatogenesis and all stages of spermatogenesis were clearly seen.…”

Melatonin Ratlarda Alloxan İle İndüklenen Diyabet Sonrası Oluşan Testiküler Hasarı ve Oksidatif Etkileri Hafifletir

“…The Melatonin Attenuates ... parameters in the DM group rats [10][11][12][13][14] . The protective effects of MLT (used herein as an antioxidant) on the testis tissue are consistent with the previous results in DM models [11,12,44] .…”

“…The MLT is a freeradical scavenger and wide-spectrum antioxidant, and it stimulates the gene expression of antioxidant and prooxidant enzymes. MLT treatment after alloxan-induced b-cell destruction has been reported recently [10][11][12][13][14] . These studies suggest that MLT treatment in DM regulates the antioxidant enzymes and decreases the degenerative changes.…”