effect of stem cell therapy versus melatonin on the changes induced by busulfan in the testes of adult rat: histological and immunohistochemicaI studies

ABSTRACT

Chemotherapy is associated with significant gonadal damage. Melatonin has been found to be a potent free radical scavenger and antioxidant. Stem cells have the capacity to generate multiple distinct cell lineages. The present study aimed to compare the effect of stem cell therapy and melatonin in the amelioration of harmful changes induced by busulfan in rat testes. Forty-three adult male rats were used in the present work. Animals were divided into the following groups group I was the control group, the rats in group II received a single dose of intraperitoneal busulfan [20 mg/kg], the rats in group III rats received 0.5 ml stem cells upon an initial dose of busulfan, the animals in group IV received a single dose of intraperitoneal melatonin [10 mg/kg] for 5 days, and the rats in group V received melatonin for 5 days upon an initial dose of busulfan. The testes were stained with Hand E, prussian blue, and immunohistochemical stains for the detection of caspase-3-positive and proliferating cell nuclear antigen [PCNA]-positive cells. Digital image analysis was used to determine the mean number of active caspase-3- positive and PCNA-positive cells. The results were compared statistically. Busulfan-treated animals showed atrophy and irregularity of the tubules. Marked depletion of germ cells was supported by an increase in the mean number of caspase-3-positive cells in the semineferous tubules. In addition, decreased proliferative capacity was observed in the present study and confirmed by a decrease in the mean number of PCNA-positive cells. Sections of the stem cell-treated group [group III] showed incomplete or partial regeneration of germ cells with an absence of elongated and rounded spermatids. Sections of the melatonin-treated group [group V] showed almost complete regeneration of germ cells with the appearance of rounded and elongated spermatids. It could be concluded that melatonin was more effective than stem cells in ameliorating busulfan-induced testicular damage