scholarly journals The Paradoxical Role of Uric Acid in Osteoporosis

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2111 ◽  
Author(s):  
Kun-Mo Lin ◽  
Chien-Lin Lu ◽  
Kuo-Chin Hung ◽  
Pei-Chen Wu ◽  
Chi-Feng Pan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Uric Acid ◽  
Bone Resorption ◽  
Bone Formation ◽  
Inflammatory Cytokines ◽  
Bone Fracture ◽  
Health Concern ◽  
Free Oxygen Radicals ◽  
Increase Bone Resorption

Because of its high prevalence worldwide, osteoporosis is considered a serious public health concern. Many known risk factors for developing osteoporosis have been identified and are crucial if planning health care needs. Recently, an association between uric acid (UA) and bone fractures had been explored. Extracellular UA exhibits antioxidant properties by effectively scavenging free radicals in human plasma, but this benefit might be disturbed by the hydrophobic lipid layer of the cell membrane. In contrast, intracellular free oxygen radicals are produced during UA degradation, and superoxide is further enhanced by interacting with NADPH oxidase. This intracellular oxidative stress, together with inflammatory cytokines induced by UA, stimulates osteoclast bone resorption and inhibits osteoblast bone formation. UA also inhibits vitamin D production and thereby results in hyper-parathyroidism, which causes less UA excretion in the intestines and renal proximal tubules by inhibiting the urate transporter ATP-binding cassette subfamily G member 2 (ABCG2). At normal or high levels, UA is associated with a reduction in bone mineral density and protects against bone fracture. However, in hyperuricemia or gout arthritis, UA increases bone fracture risk because oxidative stress and inflammatory cytokines can increase bone resorption and decrease bone formation. Vitamin D deficiency, and consequent secondary hyperparathyroidism, can further increase bone resorption and aggravated bone loss in UA-induced osteoporosis.

Mitigation of IL-1β, IL-6, TNF-α, and markers of apoptosis by ursolic acid against cisplatin-induced oxidative stress and nephrotoxicity in rats

2021 ◽  
Vol 40 (12_suppl) ◽  
pp. S397-S405
Author(s):  
Pankaj Tripathi ◽  
Saeed Alshahrani
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Uric Acid ◽  
Inflammatory Cytokines ◽  
Caspase 3 ◽  
Caspase 9 ◽  
Histological Damage ◽  
Tnf Α ◽  
Mda Content ◽  
Pro Inflammatory Cytokines

Background: Ursolic acid (UA) is a natural pentacyclic triterpenoid that is known for its benefits under several pathological conditions. Cisplatin (CP) is among the most preferred chemotherapeutic agents; however, its nephrotoxicity limits its clinical utility. Purpose: This study was aimed to determine the role of UA in the reduction of CP-induced nephrotoxicity and mitigation of pro-inflammatory cytokines and apoptosis in a rat model. Methodology: Male Wistar rats were randomized into vehicle control, CP (7.5 mg/kg), UA 10 mg/kg, and CP with UA 5 and 10 mg/kg groups. Kidney and blood samples were collected for assessment of renal function, measurement of pro-inflammatory cytokines, apoptosis markers, antioxidant activity, and tissue histology. Results: CP significantly increased the levels of serum Cr, BUN, and uric acid; it also induced histological damage reflecting the pathophysiology observed during nephrotoxicity. CP has also shown its pro-oxidant activity in kidney tissue because CP decreased the levels of GSH, SOD, and CAT; it increased the lipid peroxidation as measured by MDA content. In addition, CP significantly upregulated the activity of pro-inflammatory cytokines and expression of apoptotic markers, that is, there were increased levels of IL-1β, IL-6, TNF-α, caspase-3, and caspase-9. Two weeks of continuous treatment of UA showed significant recovery against CP-induced nephrotoxicity; UA decreased the levels of Cr, BUN, and uric acid and ameliorated histological damage. UA also downregulated the activities of IL-1β, IL-6, and TNF-α as well as expression of caspase-3 and caspase-9. Furthermore, CP-induced oxidative stress that was antagonized by UA—the levels of GSH, SOD, and CAT were significantly increased while MDA content was decreased. Conclusions: UA has a protective effect against CP-induced nephrotoxicity, which may be due to its antioxidant activity and mitigation of ILβ-1, ILβ-6, TNF-α, and markers of apoptosis.

Bone changes due to pregnancy and lactation: influence of vitamin D status

1986 ◽  
Vol 251 (4) ◽  
pp. E400-E406 ◽  
Author(s):  
P. J. Marie ◽  
L. Cancela ◽  
N. Le Boulch ◽  
L. Miravet
Keyword(s):  
Vitamin D ◽  
Bone Resorption ◽  
Bone Formation ◽  
Trabecular Bone ◽  
Formation Rate ◽  
Vitamin D Status ◽  
Bone Formation Rate ◽  
Bone Calcium ◽  
Pregnancy And Lactation ◽  
Stimulation Of

The effects of pregnancy and lactation on endosteal bone formation and resorption were evaluated in vitamin D-depleted (-D) and vitamin D-repleted (+D) rats. Pregnancy induced a marked stimulation of osteoclastic bone resorption and of static and dynamic parameters of bone formation and mineralization. Bone resorption increased independently of vitamin D status and did not correlate with plasma 1,25-dihydroxyvitamin D3 [1,25(OH)2D] levels, but it was associated with increased plasma immunoreactive parathyroid hormone (iPTH) concentrations. Stimulation of the endosteal bone formation rate was mainly impaired in D-depleted rats, resulting in trabecular bone loss, which, in -D mother rats, was associated with decreased bone ash and total bone calcium. Lactation further stimulated bone resorption and reduced the trabecular bone volume; ash weight and bone calcium content were also decreased independently of the vitamin D status and changes in plasma iPTH levels. In presence of vitamin D, the bone formation rate increased fourfold during lactation but was unchanged in -D lactating rats. During lactation, vitamin D-depleted rats lost twofold more calcified bone than +D rats because of impaired mineralization. Thus, the present study shows that both the endosteal bone resorption and formation are stimulated by pregnancy and lactation and that vitamin D is required for normal bone mineralization during the reproductive period.

Pre-Transplant Bone Status Evaluation in Patients Undergoing Allogeneic Stem Cell Transplantation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2131-2131
Author(s):  
Ibrahim Yakoub-Agha ◽  
Cecile Wibaux ◽  
Leonardo Magro ◽  
Audrey Juilliard ◽  
Isabelle Legroux-Gerot ◽  
...  
Keyword(s):  
Vitamin D ◽  
Stem Cell ◽  
Bone Resorption ◽  
Bone Formation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Serum Calcium ◽  
X Ray ◽  
Bone Status ◽  
High Bone

Abstract In view of the high observed frequency of bone events following allogeneic haematopoietic stem cell transplantation (allo-SCT), the aim of this prospective study was to evaluate pre-transplant bone status in allo-SCT patients. In the month before transplantation, bone-loss risk factors were documented for 27 patients. We measured the levels of bone remodelling markers (BRMs: plasma osteocalcin and bone & total alkaline phosphatases for bone formation; CTX and telopeptides for bone resorption), together with plasma creatinine, intact PTH, TSH, testosterone, LH, FSH, 25 OH vitamin D, serum calcium & phosphorus and calciuria. In addition, bone mineral density (BMD) at the lumbar spine, femoral neck and hips was measured using double-energy X-ray absorptiometry (DEXA). Spine X-ray measurements were also made. Bisphosphonate, oral calcium and vitamin D or testosterone were administered according to the results of the evaluation.Between June 2006 and March 2007, 13 males and 14 females underwent allo-CST for haematological malignancies. The median age at transplantation was 44 years (range: 22–60). Eighteen had received prior corticosteroid therapy, 10 were smokers and 2 had a history of alcohol abuse. All had received prior chemotherapy, including 2 patients having already undergone autologous SCT. Ten of the 14 women were post-menopausal but none was on hormone replacement therapy. The median BMI was 24 kg/m2 (19–35). The daily calcium intake was low, with a median value of 950 mg/day (467–1852). While serum calcium, phosphorus and creatinine levels were within the corresponding normal ranges for all patients, 15 individuals displayed vitamin D deficiency and 6 had calciuria < 100 mg/day. Two patients suffered from hyperparathyroidism. In terms of BRMs, the patients respectively displayed a normal profile (n=9), high bone resorption activity (n=12) or high bone formation/resorption activity (n=5). One patient had hyperthyroidism and another presented hypotestosteronaemia. Bone density results were normal in 16 patients and abnormal in 11 (41%), including 8 with osteopaenia and 3 with osteoporosis. Vertebral fractures were observed in 4 patients. Overall, 18 patients (67%) were considered as having a pathological bone status and required treatment with bisphosphonate alone (n=5), vitamin D supplementation alone (n=11) or both (n=2).This study revealed that a large proportion of allo-CST patients have pre-existing abnormal bone status and thus demonstrates the importance of pre-transplant bone status evaluation in allo-CST candidates. The implementation of appropriate bone-related treatments may reduce the frequency of post-transplant bone events.

ED-71, a novel vitamin D analog, promotes bone formation and angiogenesis and inhibits bone resorption after bone marrow ablation

Bone ◽  
2007 ◽  
Vol 40 (2) ◽  
pp. 281-292 ◽  
Author(s):  
N. Okuda ◽  
S. Takeda ◽  
K. Shinomiya ◽  
T. Muneta ◽  
S. Itoh ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Vitamin D ◽  
Bone Resorption ◽  
Bone Formation ◽  
Vitamin D Analog ◽  
Bone Marrow Ablation ◽  
Marrow Ablation

24,25(OH)2D3, bone formation, and bone resorption in vitamin D-deficient, azotemic rats

1984 ◽  
Vol 36 (1) ◽  
pp. 206-213 ◽  
Author(s):  
W. G. Goodman ◽  
D. J. Baylink ◽  
D. J. Sherrard
Keyword(s):  
Vitamin D ◽  
Bone Resorption ◽  
Bone Formation

scholarly journals The Roles of Inflammation, Oxidative Stress and the Gut-Brain Axis in Treatment Refractory Depression in Youth: Complementary and Integrative Medicine Interventions

2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Deborah R. Simkin ◽  
L. Eugene Arnold ◽  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Inflammatory Cytokines ◽  
B Vitamins ◽  
Fermented Foods ◽  
Omega 3 ◽  
Methyl Donors ◽  
Refractory Depression ◽  
Omega 6 ◽  
Pro Inflammatory Cytokines

Teen depression and suicide rates have risen despite conventional treatments. This article reviews adjunctive interventions that may improve outcomes. A search of the National Library of Medicine database used tailored searches with combinations of specific terms. Modern lifestyle is associated with increased inflammation and pro-inflammatory cytokines leading to, for instance, hyperactivation of the hypothalamic-pituitary-adrenal axis, which promotes depression. Inflammation also increases oxidative stress, leading to mitochondrial dysfunction, also associated with depression. Diets with less probiotic-containing fermented foods change the microbiome and decrease the bio-availability of mood-regulating B vitamins crucial to neurotransmitter production. Vitamin D deficiency allows increased pro-inflammatory cytokines and disrupts mitochondrial function and monoamine production. Deficiencies/insufficiencies of magnesium, Vitamin D, and B vitamins correlate with depression severity. Deficiencies of the folate and methylation cycles may lead to treatment-resistant depression. Imbalance of omega-6 and omega-3 fatty acid intake allows more pro-inflammatory eicosanoids (prostaglandins, thromboxanes, leukotrienes) from omega-6 than anti-inflammatory eicosanoids from omega-3. Refractory youth depression may be linked to abnormalities in functional biological systems, with excessive inflammation, oxidative stress, and gut-brain issues. Mediterranean diet, vitamins/minerals, omega-3 fatty acids, methyl donors, meditation, and exercise are worth considering as adjunctive treatments. More research is needed.

scholarly journals INTAKE OF A VITAMIN-MINERAL COMPLEX IS A RATIONAL WAY TO MAKE UP A CALCIUM DEFICIENCY IN CONDITIONS OF INSUFFICIENT CONSUMPTION OF DAIRY PRODUCTS BY A CHILD

2018 ◽  
Vol 17 (3) ◽  
pp. 200-206 ◽  
Author(s):  
Evgenia V. Shikh ◽  
Anna A. Makhova ◽  
Evgeny E. Emelyashenkov
Keyword(s):  
Vitamin D ◽  
Bone Resorption ◽  
Bone Formation ◽  
Calcium Intake ◽  
Dairy Products ◽  
Milk Protein ◽  
Calcium Deficiency ◽  
Food Sources ◽  
Lactase Deficiency ◽  
Milk And Dairy Products

A calcium deficiency is detected in more than 80% of children. This is the result of inadequate consumption of milk and dairy products which are the main food sources of calcium. There is a correlation between deficiency of calcium intake with food in childhood and the risk of osteopenia and osteoporosis in subsequent life periods. With insufficient exogenous intake of calcium, its concentration in the blood decreases which stimulates bone resorption. The factors that further limit the consumption of dairy products are lactase deficiency and cow's milk protein allergy. In order to ensure the intake of the necessary amount of calcium, it is advisable to use vitaminmineral complexes in children that contain not only a sufficient amount of calcium and vitamin D but also other micronutrients required for bone formation.

scholarly journals EGCG Attenuates Uric Acid-Induced Inflammatory and Oxidative Stress Responses by Medicating the NOTCH Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Hua Xie ◽  
Jianqin Sun ◽  
Yanqiu Chen ◽  
Min Zong ◽  
Shijie Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Inflammatory Cytokines ◽  
Stress Responses ◽  
Umbilical Vein ◽  
Notch Pathway ◽  
Notch 1 ◽  
Western Blots ◽  
And Oxidative Stress

Background. The aim of this study is to investigate whether (-)-epigallocatechin-3-gallate (EGCG) can prevent the UA-induced inflammatory effect of human umbilical vein endothelial cells (HUVEC) and the involved mechanisms in vitro.Methods. HUVEC were subjected to uric acid (UA) with or without EGCG treatment. RT-PCR and western blots were performed to determine the level of inflammation marker. The antioxidant activity was evaluated by measuring scavenged reactive oxygen species (ROS). Functional studies of the role of Notch-1 in HUVEC lines were performed using RNA interference analyses.Results. UA significantly increased the expressions of IL-6, ICAM-1, TNF-α, and MCP-1 and the production of ROS in HUVEC. Meanwhile, the expression of Notch-1 and its downstream effects significantly increased. Using siRNA, inhibition of Notch-1 signaling significantly impeded the expressions of inflammatory cytokines under UA treatment. Interestingly, EGCG suppressed the expressions of inflammatory cytokines and the generation of ROS. Western blot analysis of Notch-1 showed that EGCG significantly decreased the expressions of inflammatory cytokines through Notch-1 signaling pathways.Conclusions. In summary, our findings indicated that Notch-1 plays an important role in the UA-induced inflammatory response, and the downregulation of Notch-1 by EGCG could be an effective approach to decrease inflammation and oxidative stress induced by UA.

Irisin recouples osteogenesis and osteoclastogenesis to protect wear-particle-induced osteolysis by suppressing oxidative stress and RANKL production

2021 ◽  
Author(s):  
Sihan Hu ◽  
Yuan Xue ◽  
Jiachen He ◽  
Chichi Chen ◽  
Jie Sun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bone Resorption ◽  
Bone Formation ◽  
Wear Particle ◽  
Osteoclastic Bone Resorption ◽  
Bone Homeostasis ◽  
Periprosthetic Osteolysis ◽  
Osteoblastic Bone Formation

Disruption of bone homeostasis with the decrease of osteoblastic bone formation and the facilitated osteoclastic bone resorption is the leading cause of periprosthetic osteolysis. Accumulative studies indicate irisin has the...

scholarly journals Autophagy and mTOR Pathways Mediate the Potential Renoprotective Effects of Vitamin D on Diabetic Nephropathy

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Suzan A. Khodir ◽  
Rehab M. Samaka ◽  
Omnia Ameen
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Vitamin D ◽  
Diabetic Nephropathy ◽  
Creatinine Clearance ◽  
Inflammatory Cytokines ◽  
Serum Glucose ◽  
Diabetic Patients ◽  
Oxidative Stress Markers ◽  
Stress Markers

Introduction. Not only is diabetic nephropathy (DN) the most common cause of end-stage renal disease worldwide, but it also increases the risk of mortality up to fourteen times compared to normoalbuminuric diabetic patients. Aim. The aim of the current study was the evaluation of the renoprotective effects of vitamin D in DN and the possible interplay between autophagy and mTOR pathways. Materials and Methods. Fifty male Wistar albino rats were divided (10/group) into control, DN group, insulin-treated DN group, vitamin D-treated DN group, and combined insulin and vitamin D-treated DN group. Assessments of systolic blood pressure, albuminuria, creatinine clearance, serum glucose, insulin, urea, creatinine, inflammatory cytokines, oxidative stress markers, and rat kidney gene expression of mTOR were performed. Histopathological and immunohistochemical assessments of autophagy marker LC3 in rat kidneys were also performed. Results. DN was associated with significant increases in SBP, urinary albumin, serum glucose, urea, creatinine, inflammatory cytokines, MDA, and mTOR gene expression (P<0.05). However, there was significant decrease in creatinine clearance, serum insulin, GSH, and H score value of LC3 when compared with control group (P<0.05). The combination of insulin and vitamin D treatment significantly restored DN changes when compared with the other treated groups, except in oxidative stress markers where there was an insignificant difference between the combination-treated and insulin-treated groups (P>0.05). Conclusion. It has been concluded that vitamin D is a potent adjuvant therapy in treatment of DN via downregulation of mTOR gene expression, stimulation of autophagy, and antioxidant, anti-inflammatory, and hypotensive effects.

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