Agomelatine alleviates steroid-induced osteoporosis by targeting SIRT1/RANKL/FOXO1/OPG signalling in rats

Clin Exp Pharmacol Physiol. 2023 Nov 11. doi: 10.1111/1440-1681.13832. Online ahead of print.ABSTRACTOne of the major contributors to secondary osteoporosis is long-term glucocorticoid usage. Clinically used antidepressant agomelatine also has anti-inflammatory properties. Our research aimed to inspect the probable defensive effect of agomelatine against steroid-promoted osteoporosis. There were four groups of rats; group I had saline as a negative control; rats of group II had dexamethasone (0.6 mg/kg, s.c.), twice weekly for 12 weeks; rats of group III had agomelatine (40 mg/kg/day, orally), as a positive control, daily for 12 weeks; and rats of group IV had dexamethasone + agomelatine in the same previous doses combined for 12 weeks. Finally, biochemical as well as histopathological changes were evaluated and dexamethasone treatment caused osteoporosis, as evidenced by discontinuous thin cancellous bone trabeculae, minor fissures and fractures, irregular eroded endosteal surface with elevated alkaline phosphate, tartarate resistant acid phosphate (TRACP) and osteocalcin levels. Osteoprotegerin (OPG), calcium, and phosphorus levels decreased with disturbed receptor activator of nuclear factor κ B ligand (RANKL), forkhead box O1 (FOXO1), and silent information regulator 1 (SIRT1) protein expression. However, treatment with agomelatine restored the normal levels of biochemical parameters to a great extent, supported by SIRT activation with an improvement in histopathological...
Source: Clinical and Experimental Pharmacology and Physiology - Category: Drugs & Pharmacology Authors: Source Type: research