title: Anti-osteoporotic effects of an antidepressant tianeptine on ovariectomized rats.
abstract: In the current investigation, the potential alleviating effects of tianeptine against bone loss induced in ovariectomized (OVX) rats was determined. Two weeks following a bilateral ovariectomy operation, tianeptine treatment (12.5 and 25mg/kg/twice/d) was initiated and continued for twenty-eight consecutive days. Changes in serum and urinary bone turnover biomarkers and osteoclastogenesis-inducing factors were estimated. The femoral bone mineral content was estimated using inductively-coupled-plasma mass spectrometry. Morphometric alterations of distal femoral bones were observed in the cortical and trabecular structures using micro-CT. Finally, femur bones were assessed for histopathological changes. The lack of estrogen significantly increased the levels of bone turnover biomarkers and inflammatory mediators. Mineral concentrations in the femoral bones were reduced in the OVX group. Furthermore, the femoral bone micro-architecture determined using micro-CT and histopathology were significantly altered by estrogen deficiency. Tianeptine, particularly the higher dose, corrected the elevated levels of bone metabolic products and pro-inflammatory cytokines. Tianeptine also improved mineral concentrations in femoral bones and the disturbed morphometric and histopathological features in OVX rats. In conclusion, tianeptine alleviated the osteoporotic changes in OVX animals, which may be via inhibition of the hypothalamic-pituitary-adrenal axis stress and osteoclastogenesis-provoking factors, suggesting attenuation of bone matrix degradation and osteoclast stimulation.
authors.affiliation: Department of Pharmacology, College of Medicine, Al Imam Mohammad Ibn Saud Islamic University (IMSIU), P.O. Box 11623, Riyadh, 11544, Saudi Arabia.
authors.forename: Osama A
authors.initials: OA
authors.lastname: Alkhamees
authors.affiliation: Department of Dermatology and Venerology, College of Medicine, Al Imam Mohammad Ibn Saud Islamic University (IMSIU), P.O. Box 11623, Riyadh, 11544, Saudi Arabia. Electronic address: abdulazizr73@gmail.com.
authors.forename: Abdulaziz S
authors.initials: AS
authors.lastname: Al-Roujayee
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, 11544, Saudi Arabia; Department of Biomedical Dental Sciences, College of Dentistry, University of Dammam, Dammam, 31441, Saudi Arabia.
authors.forename: Hatem M
authors.initials: HM
authors.lastname: Abuohashish
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, 11544, Saudi Arabia.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D010052:Ovariectomy / Q000379:methods; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013841:Thiazepines / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D016207:Cytokines; D004967:Estrogens; D013841:Thiazepines; C050504:tianeptine
keywords: Depression; Osteoclastogenesis; Osteoporosis; Ovariectomy; Tianeptine