scholarly journals Local anti-inflammatory effect of vitamin D in acute and chronic gouty arthritis

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Blazenka Miskic ◽  
Ines Rajkovaca ◽  
Vesna Cosic
Keyword(s):  
Vitamin D ◽  
Gouty Arthritis ◽  
Anti Inflammatory ◽  
Inflammatory Effect

scholarly journals TRAF3 Modulation: Novel Mechanism for the Anti-inflammatory Effects of the Vitamin D Receptor Agonist Paricalcitol in Renal Disease

2020 ◽  
Vol 31 (9) ◽  
pp. 2026-2042 ◽  
Author(s):  
Sandra Rayego-Mateos ◽  
Jose Luis Morgado-Pascual ◽  
José Manuel Valdivielso ◽  
Ana Belén Sanz ◽  
Enrique Bosch-Panadero ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Cultured Cells ◽  
Kidney Injury ◽  
Preclinical Model ◽  
Protein Levels ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Injury Models ◽  
Inflammatory Effect

BackgroundCKD leads to vitamin D deficiency. Treatment with vitamin D receptor agonists (VDRAs) may have nephroprotective and anti-inflammatory actions, but their mechanisms of action are poorly understood.MethodsModulation of the noncanonical NF-κB2 pathway and its component TNF receptor–associated factor 3 (TRAF3) by the VDRA paricalcitol was studied in PBMCs from patients with ESKD, cytokine-stimulated cells, and preclinical kidney injury models.ResultsIn PBMCs isolated from patients with ESKD, TRAF3 protein levels were lower than in healthy controls. This finding was associated with evidence of noncanonical NF-κB2 activation and a proinflammatory state. However, PBMCs from patients with ESKD treated with paricalcitol did not exhibit these features. Experiments in cultured cells confirmed the link between TRAF3 and NF-κB2/inflammation. Decreased TRAF3 ubiquitination in K48-linked chains and cIAP1-TRAF3 interaction mediated the mechanisms of paricalcitol action.TRAF3 overexpression by CRISPR/Cas9 technology mimicked VDRA’s effects. In a preclinical model of kidney injury, paricalcitol inhibited renal NF-κB2 activation and decreased renal inflammation. In VDR knockout mice with renal injury, paricalcitol prevented TRAF3 downregulation and NF-κB2–dependent gene upregulation, suggesting a VDR-independent anti-inflammatory effect of paricalcitol.ConclusionsThese data suggest the anti-inflammatory actions of paricalcitol depend on TRAF3 modulation and subsequent inhibition of the noncanonical NF-κB2 pathway, identifying a novel mechanism for VDRA’s effects. Circulating TRAF3 levels could be a biomarker of renal damage associated with the inflammatory state.

Anti-inflammatory effect of Sustained release granules of Aceclofenac in Gouty Arthritis Rat

2021 ◽  
pp. 5729-5732
Author(s):  
Rajiv Kumar ◽  
Parminder Nain ◽  
Jaspreet Kaur ◽  
Ravi Kumar Dhawan
Keyword(s):  
Sustained Release ◽  
Therapeutic Effect ◽  
Slow Release ◽  
Standard Dose ◽  
Gouty Arthritis ◽  
Control Group ◽  
Monosodium Urate ◽  
Sustained Release Formulation ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Gout is most common painful clinical syndrome occurs due to hyperuricaemia (high serum uric acid level) and deposition of monosodium urate crystals in joints. In the current experimental study, the anti-inflammatory effect of sustained release granules of aceclofenac, was investigated on monosodium urate crystal-induced inflammation in rat. Monosodium urate is injected appropriately at a dose of 3 mg/kg body weight of a rat on right ankle to induce inflammation in joint like gouty arthritis. The percentage of joint swelling in positive control group was increased significantly (p<0.5) when compared with normal group after 1 hr, 12 hr and 24 hr with a single injection of MSU. Therapeutic effect of sustained released granules (OD) is similar to conventional released granules (BD) and possesses an anti-inflammatory effect, which could provide relief in gouty arthritis after administration of sustained release formulation of aceclofenac once in a day only. The current study clearly indicated that slow release granules of aceclofenac exerted a strong anti-inflammatory effect against gouty arthritis at standard dose once daily. It concluded that, when aceclofenac tablet is formulated with slow release granules it decreases the dosing frequency with same therapeutic effect.

scholarly journals CLINICAL EVALUATION OF POTENTIAL ANTI-INFLAMMATORY EFFECT OF VITAMIN D3 ADJUVANT THERAPY FOR CHRONIC ASTHMA IN IRAQI PATIENTS

2016 ◽  
Vol 9 (1) ◽  
pp. 139 ◽  
Author(s):  
Rasha Saadi Abbas ◽  
Manal Khalid Abdulridha ◽  
Mostafa Abdalfatah Shafek
Keyword(s):  
Vitamin D ◽  
Treatment Level ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Pre Treatment ◽  
Group 2 ◽  
To Receive ◽  
Necrosis Factor ◽  
Group 1 ◽  
Inflammatory Effect

<p><strong>Objective</strong>:<strong> </strong>This study was designed to evaluate the potential anti-inflammatory effect of vitamin D<sub>3</sub> supplementation in Iraqi patients with chronic asthma.<strong> </strong></p><p><strong>Methods: </strong>Forty-four candidate patients were diagnosed with asthma during their visit to hospital allocated as 20 patients assigned to receive conventional therapy for asthma and 24 patients assigned to receive conventional therapy for asthma plus<strong> </strong>2000 I. U vitamin D<sub>3</sub> tablet for three months period. Also, 30 apparently healthy subjects were included in the study as a control group. Pulmonary function test, serum 25-OH vitamin D levels, serum Interlukin-10 (IL-10) levels, serum tumor necrosis factor alpha (TNF-α) levels were measured before and after three months therapy.</p><p><strong>Results: </strong>After three months treatment, there was a highly significant improvement in both measured and percentage of predicted value of pulmonary function test (PFT) compared to the pre-treatment value for both group 1 and group 2 patients (<em>p</em>&lt;0.01). Also, a highly significant increase in total endogenous vitamin D level in group 2 when compared to group 1 patients after three months period (<em>p</em>&lt;0.01). Group 2 patients presented with a significant increase in mean IL-10 after three months of treatment when compared to pre-treatment level (<em>p</em>&lt;0.05). The mean TNF-α level was increased non-significantly in both study groups, but the higher level was found in group 1 patients than in group 2 patients when compared to pre-treatment level (<em>p</em>&gt;0.05).</p><p><strong>Conclusion: </strong>There was a significant increase in the level of anti-inflammatory biomarker interleukin-10 (IL-10), though no clear effect on tumor necrosis factor-α (TNF-α) was noticed after three months treatment with vitamin D<sub>3</sub> supplementation.</p>

scholarly journals Study of Effect of Vitamin D Supplementation on Selected Hepatic and Renal Parameters in T2DM with Vitamin D Deficiency

2021 ◽  
Vol 14 (4) ◽  
pp. 1975-1982
Author(s):  
Deepali S Jankar ◽  
Kanchan C Wingkar ◽  
Ajit V Sontakke ◽  
Chintamani D Bodhe
Keyword(s):  
Vitamin D ◽  
Calcium Phosphate ◽  
Liver Enzymes ◽  
Vitamin D Supplementation ◽  
Significant Rise ◽  
Blood Levels ◽  
Significant Fall ◽  
Hepatic Cells ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Introduction:- Vitamin D has been studied as modifiable risk factor in DM. Apart from its role in glucose homeostasis, the anti-inflammatory effect of vitamin D is claimed to have important effect on beta cell survival and on hepatic cells. Vitamin D is said to have anti-inflammatory, anti-proliferative and anti-fibrotic actions in liver. VDD is more prevalent in T2DM, obese and NAFLD even when these conditions occur separately. Literature states the protective effective of vitamin D on kidney. Association of VDD with albuminuria and chronic kidney disease in diabetics has also been reported. Material and Methods:- This is a type of comparative and interventional study. 63 T2DM patients aged 30 – 60 years with VDD were included. Baseline investigations determined blood levels of vitamin D, calcium, phosphate, liver enzymes (AST, ALT, ALP) and serum creatitine. Patients received vitamin D intervention orally in the dose of 2000 IU daily for 12 weeks. After 12 weeks blood levels of vitamin D, calcium, phosphate, liver enzymes (AST, ALT, ALP) and serum creatitine were determined. Results:- There was no correlation of vitamin D with urea, creatinine, calcium, phosphate, AST, ALT and ALP. There was extremely significant rise in vitamin D, significant fall in phosphate level, non-significant fall in creatinine, AST, ALT, ALP and non-significant rise in calcium, urea after 12 weeks of vitamin D supplementation. Conclusion:- There was no correlation of vitamin D with hepatic and renal parameters. Also 12 weeks of vitamin D supplementation had no significant improvement in these parameters in T2DM.

scholarly journals P0087TRAF3 MODULATION: A NOVEL MECHANISM OF THE ANTI-INFLAMMATORY EFFECTS OF VITAMIN D RECEPTOR AGONIST PARICALCITOL IN RENAL DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sandra Rayego-Mateos ◽  
Jose Luis Morgado Pascual ◽  
José M Valdivielso ◽  
Ana Sanz ◽  
Enrique Bosch panadero ◽  
...  
Keyword(s):  
Vitamin D ◽  
Renal Disease ◽  
Vitamin D Receptor ◽  
Renal Damage ◽  
Preclinical Models ◽  
Renal Inflammation ◽  
Protein Levels ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Abstract Background and Aims Tumor necrosis factor receptor-associated factors (TRAFs) are critical signaling adaptors downstream of pro-inflammatory receptors, involved in canonical and non-canonical nuclear factor-κB (NF-κB) activation. Vitamin D receptor agonists (VDRAs) exert beneficial effects in renal disease and possess anti-inflammatory properties, but the underlying mechanism remains unknown. Our aim was to investigate TRAF3 involvement on renal disease and its potential modulation by VDRAs. Method Studies were done in isolated peripheral blood mononuclear cells (PBMCs) from end-stage renal disease (ESRD) on haemodialysis (treated or not with VDRAs) patients, healthy donors or cultured renal cells. Preclinical models of renal damage were: unilateral ureteral obstruction (UUO), acute renal damage induced by Folic acid (FA) administration and TWEAK-induced renal inflammation. The effect of VDRA (paricalcitol) was tested in vitro and in vivo. Results In PBMCs isolated from ESRD, TRAF3 protein levels were downregulated compared to healthy controls, associated to activation of non-canonical NF-κB2 (downregulation of RelB or p52/NF-κB2 protein levels) and altered pro-inflammatory cytokine profile. Interestingly, treatment of those patients with the VDRA paricalcitol restored all the described features. In vitro experiments in PBMCs and tubular epithelial cells exposed to inflammatory stimuli showed that paricalcitol prevented TRAF3 downregulation, NF-κB2 activation and proinflammatory genes upregulation. Moreover, immunoprecipitation studies showed that paricalcitol diminished TRAF3 ubiquitination in the K48-linked chains and CIAP1-TRAF3 interaction. TRAF3 overexpression by CRIPS/cas9 technology mimics VDRAs effects. In preclinical models of renal damage paricalcitol inhibited renal NF-κB2 activation, reducing p52 and RelB nuclear accumulation and transcriptional activity associated to lower renal inflammation. In TWEAK-induced renal injury in VDR knockout mice, paricalcitol prevented TRAF3 downregulation and NF-κB2-dependent gene upregulation, suggesting a VDR-independent anti-inflammatory effect of paricalcitol. Conclusion The present studies identify TRAF3 downregulation as a key feature promoting inflammation in CKD identifying non-canonical NF-κB activation as a key driver of inflammation in this context. The fact that the VDR is not required for paricalcitol actions suggests novel-signaling pathways involved in the anti-inflammatory effect of paricalcitol. This may allow the design of drugs that restore TRAF3 levels but are devoid of VDR-dependent effects on mineral bone metabolism, which may limit the use of VDRAs as anti-inflammatory agents.

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