---

Background & aim: The effect of drugs on different receptors causes the effect as well as side effects of the drug. For example, dopamine drugs, in addition to their anti-Parkinsonian effects, block the upper parts of the hypothalamic-pituitary-gonad axis and cause infertility. Therefore, the aim of this study was to determine the effect of fluvoxamine on sex hormone levels and ovarian histology in guar gum after injection of bromocriptine.
 
Methods: In the present basic study conducted at Islamic Azad University in 2020, 90 fish with an average weight of 1.3 g were prepared from the female fish breeding center located in Damavand. The fish were divided into 6 groups of 15 including three intact control groups: solvent (70% ethanol) and bromocriptine and 3 treatments of bromocriptine and fluvoxamine at doses of 1, 5 and 10 mg / kg body weight of fish. The injection was given intramuscularly and intramuscularly and under the dorsal fin, so that the day after injection of 5 mg / kg bromocriptine, fluvoxamine was injected in specific doses and this process continued. 20 days after injection, their ovaries were dissected and isolated for biometrics and light microscopy. Tissue hormones 17-beta-estradiol, testosterone and progesterone were measured using a special kit using tissue fluids. The collected data were analyzed using SPSS software (version 23) and one-way ANOVA and Duncan tests. Excel 2016 software was used to draw the charts.
 
Results: The results of Estradiol and Progesterone and Gonadal index revealed that the groups receiving Fluvoxamine and Bromocriptine had a significant difference with the control group (P≤0.05), and this difference was dose dependent. The results turned out that the levels of these hormones decreased in Bromocriptine control group and increased in Fluvoxamine-receiving treatments. Light microscopy images showed that the ovarian development stage in intact control and solvent control is commonly Cortical stage, but these cells remain in the primary and secondary prenuclear stage in the control group of Bromocriptine. Also in highest dose of fluvoxamine (10mg/kg.Bw) Oocytes are in the vitellogenesis stage and the gonadal index was at its highest. It can be concluded that Bromocriptine blocks the HPG axis while Fluvoxamine restimulates it, therefore there was a possibility of the presence of Serotonin receptors on the gonadal surface.
 
Conclusion: It can be concluded that bromocriptine causes blockade of HPG axis and fluvoxamine re-stimulates the GnRH pathway, so that the ovary in the treatment receiving the highest dose of fluvoxamine was predominantly in the vitellogenesis index and more it was its value, so it is possible for the serotonin receptor to be present on the gonadal surface.
 
 

---

Background: Cellular senescence is an irreversible process in cells that is affected by various factors such as oxidative stress and inflammation, and the importance of this issue increases in its effect on neural stem cells. Fluvoxamine at appropriate concentrations provides proliferation and differentiation of neural stem cells into glial and neurons and modulates inflammatory factors. Therefore, considering the mechanism of the aging process on neural stem cells, this study investigates the effects of fluvoxamine in culture.
Materials and methods: In this experimental study, neural stem cells were first isolated from the subventricular zone of the adult male mouse brain. Neutrosphere cell colonies were formed in the presence of epidermal growth factor and fibroblast growth factor. The survival of neurospheres in fifteen groups including a control group, treatment group with 20 μM D-galactose concentration, and fluvoxamine treatment groups with different concentrations and combined D-galactose with fluvoxamine groups was measured by the MTT method. Also, the number of neurospheres, the number of cells resulting from each neutrosphere cell, and the number of senescent cells were counted. The collected data were analyzed using GraphPad software and a one-way ANOVA test.
Results:  The average data from the survival of neural stem cells in the 25 and 50 nM fluvoxamine groups significantly increased compared to the control group and decreased significantly with increasing doses (p<0.001). Also, the survival of cells in the D-galactose group significantly decreased compared to the control group (p<0.01), which showed a significant increase in the treatment with low-dose fluvoxamine compared to the D-galactose group (p<0.001) and a significant decrease in the high-dose groups. The number of neurospheres in the D-galactose group was significantly decreased compared to the control group (p<0.001). Also, the number of neurospheres in the D-galactose group with 50 nM fluvoxamine compared to the D-galactose group was significantly increased (p<0.01). The number of BrdU-positive cells in the fluvoxamine 100 group showed a statistically significant increase compared to the control group (p<0.001). The number of BrdU-positive cells in the di-galactose group also showed a statistically significant decrease compared to the control group (p<0.01). The combination treatment of di-galactose with fluvoxamine at low doses increased the number of BrdU-positive cells compared to the di-galactose group. The average number of neural stem cells in the di-galactose groups decreased significantly compared to the control group, and the combination of di-galactose with fluvoxamine at doses of 50 showed a statistical increase compared to the di-galactose group (p<0.001). The average number of senescent cells increased significantly with increasing fluvoxamine doses compared to the control group. Also, treatment with di-galactose increased the number of senescent cells compared to the control group, and treatment with di-galactose and fluvoxamine at concentrations of 25 and 50 nM showed a statistically significant decrease in the number of senescent cells compared to the di-galactose group (p<0.0001).
Conclusion: The results of this study indicate that fluvoxamine, prescribed for the treatment of major depression and obsessive-compulsive disorders, while increasing the survival and viability of cells at low doses, exhibits significant toxicity at higher doses in a dose-dependent manner. Furthermore, it elevates aging-related factors and induces aging in neural stem cells under ex vivo conditions. In other words, it reduces the survival of neural stem cells, the number of neurospheres, and the number of cells derived from each neurosphere, while simultaneously increasing the number of aged cells. These findings necessitate further investigations in both in vivo and in vitro environments.