cholecalciferol and Iron-Overload

Patients with transfusion-dependent thalassemia (TDT) show disorders in calcium metabolism. The α-Klotho protein is predominantly expressed in tissues that are involved in calcium homeostasis, and lowered levels are associated with bone disease. The aim of the study is to examine the associations between low α-Klotho status and calcium metabolism in relation to iron status in children with TDT.. Calcium, α-Klotho, parathyroid hormone (PTH), calcyphosin, vitamin D3, phosphorous, fibroblast growth factor receptor 2 (FGFR2), as well as iron and erythron biomarkers were measured in 60 children with TDT and 30 healthy control children.. A meaningful part of TDT patients showed lowered α-Klotho levels, and those children also showed low serum total and ionized calcium concentrations. TDT patients showed increased PTH, FGFR2, and calcyphosin and lowered vitamin D3 as compared with healthy children. The α-Klotho levels were significantly correlated with total and ionized calcium (positively) and with iron overload and transfusions biomarkers (inversely). Partial Least Squares path analysis showed that 40.1% of the variance in serum total calcium could be explained by the regression on α-Klotho, vitamin D3 (both positively), and calcyphosin (inversely) and that the effects of the latter are mediated by iron overload and the number of blood transfusions.. In conclusion, the iron overload in TDT and its consequences may induce lowered levels of α-Klotho which in turn may lead to lower calcium thereby explaining at least in part the effects of TDT on bone metabolism including spontaneous pathological fractures, osteoporosis, osteopenia, and skeletal deformities.

Topics: Biomarkers; Calcium; Child; Cholecalciferol; Humans; Iron; Iron Overload; Parathyroid Hormone; Thalassemia

Chronic iron overload could induce nephropathy via oxidative stress and inflammation, and chelating therapy has limited efficacy in removing excess intracellular iron. Although vitamin D (VD) has shown potent antioxidant and anti-inflammatory effects, as well contribute to iron homeostasis, none of the previous studies measured its potential remedial effects against chronic iron toxicity.. To measure the alleviating effects of deferasirox (DFX) and/or vitamin D (VD) single and combined therapies against nephrotoxicity induced by chronic iron overload.. iron-induced nephrotoxicity was associated with dysregulations in renal VD-system together with renal oxidative stress, inflammation, and apoptosis. While DFX reduced systemic iron, VD monotherapy showed better attenuation of renal iron concentrations and tissue damage. Nonetheless, the co-therapy approach exhibited the maximal remedial effects, possibly by enhanced modulation of renal iron-homeostatic molecules alongside reducing systemic iron levels.. All data generated or analysed during this study are included in this published article [and its Supplementary information files].

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Caspase 3; Cholecalciferol; Deferasirox; Ferritins; Hepcidins; Hydrogen Peroxide; Inflammation; Interleukin-10; Interleukin-6; Iron; Iron Overload; Kidney; Low Density Lipoprotein Receptor-Related Protein-2; Male; Oxidative Stress; Rats; Receptors, Transferrin; Superoxide Dismutase-1; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D3 24-Hydroxylase