cholecalciferol and Pulmonary-Fibrosis

For many years vitamin D3 was known only as a regulator of the calcium-phosphate and water-electrolyte balances. Recent studies have paid special attention to other biological effects of calcitriol (the bioactive form of vitamin D3) with particular emphasis on its influence on immune function. Thus, any alterations, especially deficiencies, in the physiological level of calcitriol have serious health consequences. The aim of the study was to summarise the current state of knowledge concerning the role of vitamin D3 in selected pulmonary diseases.. The review was based on data obtained from articles published in PubMed between 2000-2022. Papers were reviewed for scientific merit and relevance.. In the reviewed literature, much attention was paid to clinical studies focused on the role of vitamin D3 in the pathogenesis of selected respiratory diseases. As revealed in research over the last two decades, vitamin D3 deficiency increases the risk and worsens the course of asthma, cystic fibrosis, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, as well as COVID-19. Surprisingly, vitamin D supplementation has not always proved to be an effective therapeutic strategy. The review also presents the unique concept of the possibility of using vitamin D3 in the prevention and treatment of pulmonary fibrosis in the course of hypersensitivity pneumonitis.. Due to the multiplicity and variety of factors that affect the metabolism of vitamin D3, effective counteracting, and even more eliminating the negative consequences of disorders in the level and activity of calcitriol in the respiratory tract, seems to be a breakneck action. On the other hand, only a deep understanding of the role of calcitriol in the pathogenesis of lung diseases provides the chance to develop an effective therapy.

Topics: Calcitriol; Cholecalciferol; COVID-19; Humans; Pulmonary Fibrosis; Vitamin D; Vitamin D Deficiency

We aimed to evaluate whether pulmonary fibrosis occurs in type 2 diabetes rat models and whether VD3 can prevent it by inhibiting pyroptosis.. Sprague-Dawley rats were assigned to normal control (NC), diabetic model control (MC), low-dose VD3 (LVD), medium-dose VD3 (MVD), high-dose VD3 (HVD) and metformin positive control (PC) groups. Type 2 diabetes model was induced by a high-sugar, high-fat diet combined with STZ injection, and subsequently intervened with VD3 or metformin for 10 weeks. Blood glucose, body weight, food intake, water intake, urine volume, morphology, lung hydroxyproline level, immunohistochemistry, TUNEL staining, inflammatory cytokines secretion and related protein expression were analyzed.. Diabetic rats exhibited significant impairments in fasting blood glucose, insulin resistance, body weight, food intake, water intake, and urine volume. While morphological parameters, diabetic rats exhibited severe lung fibrosis. Intriguingly, VD3 intervention reversed, at least in part, the diabetes-induced alterations. The expression of pyroptosis-related proteins was up-regulated in diabetic lungs whereas the changes were reversed by VD3. In the meanwhile, SIRT3 expression was down-regulated in diabetic lungs while VD3 up-regulated it.. Fibrotic changes were observed in diabetic rat lung tissue and our study indicates that VD3 may effectively ameliorate diabetic pulmonary fibrosis via SIRT3-mediated suppression of pyroptosis.

Topics: Animals; Apoptosis; Blood Glucose; Body Weight; Cholecalciferol; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Metformin; Pulmonary Fibrosis; Pyroptosis; Rats; Rats, Sprague-Dawley; Sirtuin 3

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrotic lung disease. However, there are insufficient drugs available for IPF treatment, and the currently used drugs are accompanied by many adverse reactions. Deficiency of vitamin D3 (VD3) in the development of IPF and the potential role of VD3 in the treatment of IPF have attracted increasing attention. In vivo experimental results showed that VD3 could increase the survival rate in bleomycin (BLM)-induced models, relieve lung inflammation, reduce hydroxyproline content, and inhibit collagen deposition and cell apoptosis. We further performed proteomics analysis and screened 251 target proteins that reflect VD3 intervention in BLM-induced animal models. These target proteins were involved in acute inflammation, oxidative stress, antioxidant activity and extracellular matrix binding. Combined with the comprehensive analysis of clinical samples, PSAT1 was screened out as a candidate target related to IPF disease and VD3 treatment. Through further computational analysis, the MAPK signaling pathway was considered to be the most probable candidate pathway for VD3 function targeting IPF. In in vivo experiments, VD3 inhibited BLM-induced expression of PSAT1 and phosphorylation of p38 and ERK1/2 in mouse lung tissue. The experiments of cell proliferation and western blot confirmed that VD3 inhibited the expression of PSAT1 and the activation of the mitogen-activated protein kinase (MAPK) pathway in human pulmonary fibroblasts (HPF). Furthermore, experiments with transfection plasmids overexpressing PSAT1 proved that VD3 could attenuate the proliferation and differentiation of HPF by suppressing the effect of PSAT1 on the MAPK signaling pathway. Finally, we confirmed that vitamin D receptor (VDR) could occupy the PSAT1 promoter to reveal the transcriptional regulation effect of VD3 on PSAT1. In conclusion, VD3 exerted a therapeutic effect on IPF by down-regulating the MAPK signaling pathway via targeting the expression of PSAT1.

Topics: Animals; Antibiotics, Antineoplastic; Bleomycin; Calcium-Regulating Hormones and Agents; Cell Line; Cell Survival; Cholecalciferol; Fibroblasts; Humans; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Pulmonary Fibrosis; Random Allocation

Hypovitaminosis D is a risk factor for transplant-related osteoporosis. Its contribution to severe hypocalcemia in transplant recipients is less well recognized. We present 2 cases to illustrate how risk factors specific to transplant recipients significantly increase the risk of development of severe hypocalcemia, on a background of unrecognized vitamin D deficiency. Regular surveillance of calcium homeostasis should be incorporated into routine clinical care of transplant recipients.

Topics: Calcitriol; Calcium; Cholecalciferol; Cystic Fibrosis; Humans; Hypocalcemia; Immunosuppressive Agents; Lung Transplantation; Magnesium; Male; Middle Aged; Pulmonary Fibrosis; Reference Values; Treatment Outcome; Vitamin D; Vitamin D Deficiency

Bleomycin (BLM) is a chemotherapeutic agent against different carcinomas, one dose of which causes dependent pulmonary fibrosis. The present study was taken up in order to measure the retinyl ester, alpha-tocopherol and cholecalciferol (vitamin D(3)) level in lung tissue in the rats following BLM-induced fibrosis. Fourteen rats were randomly divided into two groups as a control and a BLM group. On the day of the experiment, the BLM group rats were instilled with BLM (7.5 mg/kg) and the control group with sterile saline intratracheally. Fourteen days after instillation, rats in each group were sacrificed and the lungs were prepared for histopathological examination and determination of the vitamin levels with a HPLC system. The levels of retinyl ester, alpha-tocopherol and vitamin D(3) in the lungs of the BLM group were determined to be lower than in the controls. There was statistically significant difference for the alpha-tocopherol and vitamin D(3) concentrations compared to the control group (p<0.01, p<0.001), respectively. According to these results in pulmonary fibrosis, vitamins were consumed by the lung tissue and their levels decreased.

Topics: Acute Lung Injury; alpha-Tocopherol; Animals; Antibiotics, Antineoplastic; Bleomycin; Cholecalciferol; Lung; Male; Pulmonary Fibrosis; Random Allocation; Rats; Rats, Wistar; Vitamin A