The Effect of Irisin on Thyroid Hormone Levels in Chronic Paroxetine-Treated Rats.

It is known that serotonin reuptake inhibitors (SSRIs), which are widely used in mood disorders, affect the hypothalamic-pituitary-thyroid axis activity. In this study, we investigated the effect of paroxetine, an SSRI, on thyroid hormone levels in rats. We also examined the role of irisin, a newly discovered potential regulatory hormone for metabolism, on paroxetine-induced changes. A total of 64 Sprague-Dawley female and male rats were randomly divided into four subgroups for each gender and treated as follows: sham-operated control (vehicle), paroxetine (treated with 20 mg/kg paroxetine by oral gavage), irisin (100 ng/kg/day for 28 days with mini-osmotic pumps), and paroxetine + irisin group (n = 8). Serum fasting free triiodothyronine (fT3) and free thyroxine (fT4) levels were measured by automated chemiluminescence method. Serum thyroid-stimulating hormone (TSH) level was determined with enzyme-linked immunosorbent analysis (ELISA). Compared to the sham control group (p < 0.05), the significantly reduced fT4 and TSH serum levels in paroxetine-treated male animals were markedly increased by subcutaneous irisin perfusion. fT3 levels significantly increased in both irisin (4.35 ± 0.17 pq/mL) and paroxetine + irisin groups (4.51 ± 0.19 pq/mL) compared to sham control (3.60 ± 0.23 pq/mL) and paroxetine groups (3.57 ± 0.12 pq/mL) (p < 0.05). It was observed that serum fT3, fT4, and TSH levels decreased in female animals receiving paroxetine compared to the sham control group. Subcutaneous administration of irisin increased these hormone levels. However, these changes were not statistically significant. These results suggested that irisin may play a role in the mechanism underlying the beneficial effects of exercise in preventing SSRI-related side effects by increasing thyroid hormone levels, which were decreased by paroxetine.

Beneficial effects of irisin in experimental paroxetine-induced hyperprolactinemia.

OBJECTIVE: It is known that selective serotonin reuptake inhibitors (SSRIs), represent an important and effective treatment of depression and other psychological disorders, these medications can increase prolactin levels mainly through activation of the serotonergic pathway. In this study, we aimed to determine the beneficial effects of irisin on paroxetine, a SSRI, induced hyperprolectinemia and in some other reproductive hormonal changes associated with hyperprolactinemia. METHODS: Thirty two male Spraque-Dawley rats were used and divided into four groups including sham-operated control (vehicle), irisin (100 ng/kg/day for 28 days with mini-osmotic pumps), paroxetine (treated with 20 mg/kg paroxetine by oral gavage), irisin and paroxetine+irisin groups (n = 8). Serum prolactin (PRL), kisspeptin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and 5-alpha reductase levels were determined with enzyme-linked immunosorbent analysis (ELISA). RESULTS: In animals treated with paroxetine, PRL level increased and testosterone level decreased significantly (p < 0.05). Serum LH level was significantly increased in the group, but no significant changes were observed in the FSH, kisspeptin and 5-alpha reductase levels. Serum prolactin levels was significantly decreased in the group treated with irisin. While no significant difference was observed in kisspeptin, FSH and 5-alpha reductase levels, an increase in serum LH and testosterone levels with irisin administration (p < 0.05). CONCLUSION: In conclusion, chronic irisin exposure may reverse paroxetine-induced hyperprolactinemia. These results indicate that irisin may have the potential to be used as a therapeutic agent by primarily affecting paroxetine-induced increased prolactin and decreased testosterone levels.