Unraveling the Role of Melatonin/Quercetin in Attenuating the Metabolic and Bone Turnover Alternations in Iron Treated-Ovariectomized Female Rats

Abstract
Background: Iron accumulation is involved in many of postmenopausal associated disorders, like osteoporosis.
Aim of Study: This study was designed to evaluate the possible role of iron accumulation in deteriorating the ova-riectomy-induced metabolic and bone remodeling alterations with the possible protective effect of melatonin and quercetin in this respect.
Material and Methods: 40 female albino rats were divided into 5 equal groups, 8 rats each; Group 1: Control sham operated group, received intraperitoneal injections of normal saline, 3 times/week after sham operations, Group 2: Ovariec-tomized (OVX) group, received the same saline treatments after bilateral ovariectomy, Group 3: Iron treated-OVX group (F-OVX), received intraperitoneal injections of 0.04g/kg ferric ammonium citrate 3 times a week after bilateral ovariectomy, Group 4: Melatonin + iron treated-OVX group (MF-OVX), received subcutaneous melatonin injections (10mg/kg) daily after bilateral ovariectomy, Group 5: Quercetin + iron treated-OVX group (QF-OVX), received intraperitoneal quercetin injection of 10mg/kg/day after bilateral ovariectomy.
At the end of the experimental regimen (4 weeks), blood samples were collected and centrifuged, the obtaining serum was used for determination of iron, ferritin, Malondialdehyde (MDA), Total Antioxidant Capacity (TAC) glucose, insulin and insulin resistance (using HOMA-IR equation). Moreover, the serum Total Cholesterol (TC), High Density Lipoprotein-Cholesterol (HDL-C), Low Density Lipoprotein-Cholesterol (LDL-C) and Triglycerides (TG) were assayed along with bone turnover markers including; serum Osteocalcin (OC), Bone Specific Alkaline Phosphatase (BALP) Cross-linked Carboxy-terminal telopeptide of type I collagen (CTX-I) and tartrate-resistant acid phosphatase 5b (TRACP5b). Further-more, livers were removed for determination of liver iron, MDA and TAC levels.
Results: Iron treatment in OVX rats further exacerbated the ovariectomy induced alterations in oxidative status, indi-cated by increased MDA and decreased TAC in both serum and liver tissue, metabolic status, indicated by significantly elevated serum TC, LDL-C, TG, glucose and HOMA-IR levels, and bone turnover status, indicated by significant decrease in serum markers of bone formation (OC, BALP) and increase in those of bone resorption (CTX-I, TRACP5b), in F-OVX group compared to OVX group. On the other hand, treatment of F-OVX rats with either melatonin or quercetin significantly mitigated all these alterations, which was in concomitance with improvement of the iron status indicated by significant decrease in serum and liver iron along with serum ferritin levels, in MF-OVX and QF-OVX groups com-pared to F-OVX group.
Conclusion: Melatonin and quercetin improved the met-abolic and bone turnover alternations, induced by iron accu-mulation in treated F-OVX rats, possibly via their iron chelat-ing, antioxidant, insulin sensitizing, hypolipidemic and anti-osteoporotic effects, as recorded in this rat model.