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Published on: April 1, 2015
Melatonin and testicular damage in busulfan treated mice
Mehri Mirhoseini1, Ghasem Saki2, Masoud Hemadi3
1Department of Anatomy, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran.
Background:
Advancement in the treatment of various types of cancer has led to greater patient survival. These treatments essentially have toxic effects on different kinds of cells, such as germ cells. Infertility as one of the side effects of cancer treatment has changed the quality of life of young cancer survivors dramatically. Melatonin is an antioxidant with receptors in the reproductive systems.
Objectives:
We supposed that melatonin, as an antioxidant, may protect testis against the toxic effects of the drugs.
Materials And Methods:
In this experimental study, three groups with seven mice each, were allocated. The control group received normal saline for two months, and the busulfan group received a single dose of 40 mg/kg busulfan intra-peritoneally, and the melatonin group received 20 mg/kg melatonin daily for two months, 45 days after a single dose of busulfan. Next, after decapitation and removal of the testis, tissues were fixed in Bouin's solution and stained by H&E and TUNEL. The sections were evaluated, assessing morphology and spermatogenesis.
Results:
In this research, a significant reduction in Johnson's criteria in the busulfan group (Mean rank = 15.50) was found versus the control group (Mean rank = 45.50), P < 0.001 and in the melatonin group (Mean rank = 45.50) compared to the busulfan group (Mean rank = 15.50), P < 0.001. There was a significant difference between the melatonin and control groups, P < 0.05. In addition, a significant decrease in seminiferous tubule diameter was observed in the busulfan group (763.2 ± 104.41) versus the control group (855.4 ± 52.35), P < 0.01 and melatonin group (834.2 ± 87.26), P < 0.05. Testicular epithelium height was significantly decreased in the busulfan group (Mean rank = 14.60) compared to the control group (Mean rank = 26.40), P < 0.01 and in the busulfan group (Mean rank = 14.95) in comparison with the melatonin group (Mean rank = 26.05), P < 0.01. Also melatonin group (Mean rank = 25.42) showed a significant reduction in epithelium height compared to the control group (Mean rank = 35.58), P < 0.05. Spermatogenesis was impaired in the busulfan group. Although melatonin reduced the rate of apoptosis in the busulfan group, yet it could not remove all apoptotic cells.
Conclusions:
This study indicated that melatonin ameliorates the cytotoxic effects of busulfan on germ cells.
Insights
Melatonin, an antioxidant, was investigated for its protective effects on testicular function following chemotherapy. This study found that melatonin can ameliorate the damaging effects of busulfan on germ cells and spermatogenesis.
Area of Science:
- Reproductive Biology
- Toxicology
- Oncology
Background:
- Cancer treatments can cause infertility by damaging germ cells.
- Melatonin is an antioxidant with potential protective effects on reproductive systems.
Purpose of the Study:
- To investigate if melatonin can protect the testis from chemotherapy-induced toxicity.
- To evaluate the antioxidant properties of melatonin in mitigating drug-induced testicular damage.
Main Methods:
- Experimental study involving three groups of mice: control, busulfan-treated, and busulfan + melatonin-treated.
- Busulfan was administered to induce testicular toxicity.
- Melatonin was administered daily to assess its protective effects on testicular morphology and spermatogenesis.
Main Results:
- Busulfan significantly reduced Johnson's criteria, seminiferous tubule diameter, and testicular epithelium height.
- Melatonin administration partially reversed these negative effects, improving spermatogenesis and reducing apoptosis.
- While melatonin showed protective effects, it did not completely eliminate all apoptotic cells.
Conclusions:
- Melatonin demonstrates a protective effect against busulfan-induced testicular toxicity.
- Melatonin ameliorates the cytotoxic impact of chemotherapy drugs on germ cells.
- Further research may explore optimal melatonin dosages for cancer patients experiencing treatment-related infertility.
