The effect of glutathione and buserelin on the stereological parameters of the hypothalamus in the cyclophosphamide-treated mice

•Cyclophosphamide decreased the hypothalamus volume, its neuron number and increased cell death.•Glutathione and buserelin almost preserved the hypothalamus structure in its normal condition.•Buserelin is more effective than glutathione to decrease the side effects of this drug on the hypothalamus. New anticancer drugs have increased the survival and fertility rates in young patients. These drugs (i.e., cyclophosphamide; Cyc) have some side effects on the hypothalamus and fertility. One possible chemical for reducing these side effects is thiol or GnRH agonist. This study aimed to evaluate the capability of these agents for reducing the cyclophosphamide effects on the hypothalamus. Sixty-three female mice were randomly assigned into seven groups. All groups including the control group had free access to water and mouse chow ad libitum. The sham group received normal saline. The Glu and Bus groups received glutathione (Glu) and buserelin (Bus) daily for 16 days, while the Cyc group received only cyclophosphamide as a single dose; the Cyc + Glu and Cyc + Bus groups, in addition to cyclophosphamide, received glutathione and buserelin, respectively. The volume of the hypothalamus, its neuron number, and dead neurons were evaluated using stereological methods. There was no significant difference in the evaluated stereological parameters between the control and sham groups. However, the animals which received Cyc showed a decrease in the volume of the hypothalamus and its neuron number and density and an increase in cell death as compared with the control group. The treatment of the mice that received Cyc with Glu or Bus prevented these changes. This study showed that both GnRH agonist and thiol preserved or improved structural changes in the hypothalamus caused by cyclophosphamide in mice, suggesting that using thiol and especially GnRH agonist along with chemotherapy drugs may have protective effects on fertility.