Effect of Long-Term Treatment with Fluoxetine, Clomipramine and St. John's Wort Extract on Bone Turnover in Female Irradiated Rats

Aim: The study aimed at evaluating the bone turnover rate in irradiated female rats treated daily with fluoxetine, clomipramine or St. John’s wort extract for 8 weeks. Material and Methods: 40 rats were randomly classified into 5 experimental groups: normal, irradiated control, irradiated fluoxetine, irradiated clomipramine and irradiated St. John’s wort extract treated groups. The irradiated animals were exposed to a total dose of 15 Gy, fractionated over 5 weeks to small doses each of 1 Gy (day after day). Bone turnover rate biomarkers [serum osteocalcin (OC), urinary hydroxyproline/ creatinine ratio (Hpr/ Cr), urinary calcium/creatinine ratio (Ca/Cr)], hypothalamic pituitary adrenal [serum corticosterone], thyroid activities [serum thyroxin (T4) and thyrotrophin (TSH)], antioxidant [serum total antioxidant capacity (TAC) and malondialdehyde (MDA)] and pro-inflammatory biomarkers [serum tumor necrosis factor-alpha (TNF-α)] were done after 8 weeks from the 1st exposure to radiation. Histopathological investigations were also performed. Results: The present results revealed that irradiation induced a significant decrease in serum OC by 43.6%, and a significant increase of Hpr/ Cr and Ca/Cr by 186.4% and 192.4%, respectively. Irradiated rats showed also a significant increase in serum corticosterone, TNF-α and MDA as well as a significant decrease in serum T4, TSH levels and TAC. Treatment of irradiated rats with St. John’s wort extract, fluoxetine or clomipramine ameliorated most of the changes caused by bone-irradiation. The latter findings were confirmed by histological examination of bone tissue. Conclusions: St. John’s wort extract offers a therapeutic potential on bone comparable to traditional antidepressants like fluoxetine or clomipramine in irradiated female rats