Effects of fluoride on insulin signaling and bone metabolism in ovariectomized rats

Abstract

Fluoride is an essential trace element for the maintenance of bone health owing to its capacity to stimulate proliferation and osteoblastic activity that can lead to increased bone formation. However, excessive sodium fluoride (NaF) intake can impair carbohydrate metabolism thereby promoting hyperglycemia, insulin resistance, and changes in insulin signaling. Thus, this study aimed to evaluate the effect of chronic treatment with NaF in bone metabolism, insulin signaling, and plasma concentrations of glucose, insulin, tumor necrosis factor-α (TNF-α), osteocalcin (OCN), and fluoride in ovariectomized rats. Thirty-two ovariectomized Wistar rats were randomly distributed into two groups: Control (OVX-C) and those undergoing treatment with NaF (50mg F/L) in drinking water for 42days (OVX-F). Glucose and insulin levels were assessed, followed by homeostasis model assessment of insulin resistance (HOMA-IR). Akt serine phosphorylation was evaluated by western blotting. Plasma concentrations of TNF-α and OCN were evaluated by ELISA. The left and right tibia was collected for immunohistochemical and histomorphometric analysis, respectively. Chronic treatment with NaF promoted insulin resistance, decreased insulin signal, increased plasma concentration of insulin, fluoride, OCN and TNF-α, decreased trabecular bone area of the tibia, and caused changes in bone metabolism markers in ovariectomized rats. These results suggest the need for caution in the use of NaF for the treatment of osteoporosis, especially in postmenopausal woman.

Haematological evaluation of sodium fluoride toxicity in oryctolagus cunniculus

“…Fluoride can be consumed from soil, water, and vegetation. Skeletal and dental Fluorosis, stiffness of the joints and emaciation usually result from chronic fluoride toxicity [3] , [4] , [5] , [6] . Like other Hemotoxic agents fluoride also shows deleterious effects on reproductive capacity of animals and their milk production [7] , [8] , [9] , [10] .…”

Fluoride Exposure Induces Inhibition of Sodium/Iodide Symporter (NIS) Contributing to Impaired Iodine Absorption and Iodine Deficiency: Molecular Mechanisms of Inhibition and Implications for Public Health

“…A significant effect of F on OC expression has been found to occur in adults at serum F levels of 1.0 μM [154] or when urinary F levels exceed 0.62 mg/L in adolescent children [155]. Consistent with this data, several in-vivo studies have reported that chronic F exposure enhances plasma insulin levels and promotes insulin resistance in rodents [211,212,213,214,215]. A similar association has also been found in humans chronically exposed to F [216].…”

Metabolic Syndrome Features: Is There a Modulation Role by Mineral Water Consumption? A Review

“…This might have resulted from the quite distinct fluoride content of the mineral-rich waters (being the main difference between these 2 waters: lower in Pérez-Granados et al [58]) and the low-sodium diet of the Schoppen et al volunteers [61]. Nevertheless, it should pointed out that fluoride modulation of insulin secretion, action and clearance is still not completely clarified [75,146]. In contrast, NaCl restriction has been revealed to deteriorate glucose tolerance and high NaCl intake to regulate glucose homeostasis (the latter through adiponectin production) [147,148,149,150].…”