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Kowsalya R, Jagatheesh K, Pavan Kumar Padarthi, Elangovan N*
International Journal of Bioassays , 2013,
Abstract: Lipocalins as biochemical markers of disease have been extensively used. The clinical indications relate to almost any field of medicine, such as inflammatory disease, cancer, lipid disorders, liver and kidney function. Lipocalins are mainly extracellular carriers of lipophilic molecules, though exceptions with properties like prostaglandin synthesis and protease inhibition are observed for specific lipocalins. Lipocalin 2, a member of the lipocalin family that carries small lipophilic ligands, has gained recent attention as both a potential biomarker and a modulator of human cancers. Neutrophil gelatinase-associated lipocalin, also known as lipocalin 2, has been originally identified as a 25 kDa protein covalently linked to neutrophil gelatinase B. It is an acute phase protein involved in diverse physiological processes with an important role in intracellular iron transport. Moreover, lipocalin 2 is involved in the physiopathology of neoplastic process. Lipocalin 2 is a protein that has garnered a great deal of interest in multidisciplinary fields over the last two decades since its discovery. This review focuses on lipocalin 2 and its function.
Neutrophil Gelatinase-Associated Lipocalin: Its Response to Hypoxia and Association with Acute Mountain Sickness  [PDF]
Adrian Mellor,Christopher Boos,Mike Stacey,Tim Hooper,Chris Smith,Joe Begley,Jo Yarker,Rick Piper,John O'Hara,Rod King,Steve Turner,David R. Woods
Disease Markers , 2013, DOI: 10.1155/2013/601214
Abstract: Acute Mountain Sickness (AMS) is a common clinical challenge at high altitude (HA). A point-of-care biochemical marker for AMS could have widespread utility. Neutrophil gelatinase-associated lipocalin (NGAL) rises in response to renal injury, inflammation and oxidative stress. We investigated whether NGAL rises with HA and if this rise was related to AMS, hypoxia or exercise. NGAL was assayed in a cohort ( ) undertaking 6 hours exercise at near sea-level (SL); a cohort ( ) during 3 hours of normobaric hypoxia (FiO2 11.6%) and on two trekking expeditions ( ) to over 5000?m. NGAL did not change with exercise at SL or following normobaric hypoxia. During the trekking expeditions NGAL levels (ng/ml, mean ± sd, range) rose significantly ( ) from 68 ± 14 (60–102) at 1300?m to 183 ± 107 (65–519); 143 ± 66 (60–315) and 150 ± 71 (60–357) at 3400?m, 4270?m and 5150?m respectively. At 5150?m there was a significant difference in NGAL between those with severe AMS ( ), mild AMS ( ) or no AMS ( ): 201 ± 34 versus 171 ± 19 versus 124 ± 12 respectively ( for severe versus no AMS; for mild versus no AMS). In summary, NGAL rises in response to prolonged hypobaric hypoxia and demonstrates a relationship to the presence and severity of AMS. 1. Introduction Acute mountain sickness (AMS) occurs during exposure to high altitude (HA) and is a clinical syndrome characterised by headache, insomnia, malaise, and gastrointestinal symptoms. It is common, developing in 10–30% at 2500–3000 meters [1] and in up to 60% of those ascending to around 4500 meters [2]. It causes significant morbidity and is a challenging clinical condition in remote environments. A biochemical marker of AMS, particularly one available as a point-of-care test (POC), could have widespread clinical utility. The pathophysiology of AMS is not clearly understood but involves alterations in fluid balance, endothelial function, vascular permeability, inflammation, and oxidative stress. The renal response to HA is an important factor in acclimatization, and HA exposure leads to renal arteriole constriction and relative hypoxia [3, 4]. Despite the relative renal hypoxia, marked rises in creatinine or overt renal failure are generally not observed. NGAL (neutrophil gelatinase-associated lipocalin) is a 25?kDa peptide, part of the lipocalin family of small soluble proteins. It is produced in a number of human tissues, notably the distal nephron but also in the lung [5] NGAL rises rapidly in the nephron in response to a renal insult and an NGAL ≥150?ng/mL following acute kidney injury (AKI) is predictive of acute renal
Correlation between Serum Neutrophil Gelatinase Associated Lipocalin and Burn Severity: A Pilot Study  [PDF]
Sungjun Lee, Suyeol Lee, Youngwhan Choi, Song Vogue Ahn, Cheonjae Yoon, Jungsuk Lee
Journal of Biosciences and Medicines (JBM) , 2017, DOI: 10.4236/jbm.2017.51002
Abstract: The severity of an initial burn injury is critical for determining the treatment plan and prognosis of burn patients. Here, we measured serum neutrophil gelatinase-associated lipocalin (NGAL) levels to determine whether NGAL can be used as a biomarker for severity of burn injuries. A study of the demographic, clinical, and laboratory markers for various organ damage was performed at Bestian Burn Center (n = 10 healthy people, n = 31 patients). NGAL and organ damage marker levels were measured in 31 patients with severe burns within 2 - 3 days following their admission to the intensive care unit. Serum NGAL level of the expired patients was 788.5 (685.0 - 998.0) pg/mL, whereas that of the discharged patients was 421.2 (356.2 - 480.6) pg/mL, showing that the initial serum NGAL level can be used to estimate mortality. We also determined the correlation between serum NGAL level and the currently used severity markers (total body surface area burned and abbreviated burn severity index) and confirmed that serum NGAL level could be used as a severity marker. We also found that serum NGAL level was correlated with damage of organs such as the liver, kidney, heart, and respiratory organs in patients with severe burns.
Discrepancy between mRNA and Protein Expression of Neutrophil Gelatinase-Associated Lipocalin in Bronchial Epithelium Induced by Sulfur Mustard
Majid Ebrahimi,Mehryar Habibi Roudkenar,Abbas Ali Imani Fooladi,Raheleh Halabian,Mostafa Ghanei,Hisatake Kondo,Mohammad Reza Nourani
Journal of Biomedicine and Biotechnology , 2010, DOI: 10.1155/2010/823131
Abstract: Sulfur mustard (SM) is a potent vesicant that has been employed as a chemical weapon in various conflicts during the 20th century. More recently, mustard was used in the Iraq conflict against Iranian troops and civilians. At the present time there are more than 40.000 people suffering from pulmonary lesions special bronchiolitis obliterans (BOs) due to mustard gas. SM increases the endogenous production of reactive oxygen species (ROS). Neutrophil Gelatinase-associated Lipocalin 2 (Lcn2, NGAL) is a member of the lipocalin superfamily for which a variety of functions such as cellular protection against oxidative stress have been reported. Ten normal and Twenty SM-induced COPD patient individuals were studied. Assessment of NGAL expressions in healthy and the patients endobrinchial biopsies were performed by semiquantitative RT-PCR, real-time RT-PCR, and Immunohistochemistry analysis. While Normal control samples expressed same level of mRNA NGAL, expression level of mRNA-NGAL was upregulated about 1.4- to 9.8-folds compared to normal samples. No significant immunoreactivity was revealed in both samples. As we are aware this is the first report of induction of NGAL in patients exposed to SM. NGAL may play an important role in cellular protection against oxidative stress toxicity induced by mustard gas in airway wall of patients.
Association between Plasma Neutrophil Gelatinase Associated Lipocalin Level and Obstructive Sleep Apnea or Nocturnal Intermittent Hypoxia  [PDF]
Kimihiko Murase, Kiyoshi Mori, Chikara Yoshimura, Kensaku Aihara, Yuichi Chihara, Masanori Azuma, Yuka Harada, Yoshiro Toyama, Kiminobu Tanizawa, Tomohiro Handa, Takefumi Hitomi, Toru Oga, Michiaki Mishima, Kazuo Chin
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0054184
Abstract: Background Both obstructive sleep apnea (OSA) and a novel lipocalin, neutrophil gelatinase associated lipocalin (Ngal), have been reported to be closely linked with cardiovascular disease and loss of kidney function through chronic inflammation. However, the relationship between OSA and Ngal has never been investigated. Objectives To evaluate the relationship between Ngal and OSA in clinical practice. Methods In 102 patients, polysomnography was performed to diagnose OSA and plasma Ngal levels were measured. The correlations between Ngal levels and OSA severity and other clinical variables were evaluated. Of the 46 patients who began treatment with continuous positive airway pressure (CPAP), Ngal levels were reevaluated after three months of treatment in 25 patients. Results The Ngal level correlated significantly with OSA severity as determined by the apnea hypopnea index (r = 0.24, p = 0.01) and 4% oxygen desaturation index (ODI) (r = 0.26, p = 0.01). Multiple regression analysis showed that the Ngal level was associated with 4%ODI independently of other clinical variables. Compliance was good in 13 of the 25 patients who used CPAP. Although the OSA (4%ODI: 33.1±16.7 to 1.1±1.9/h, p<0.01) had significantly improved in those with good compliance, the Ngal levels were not significantly changed (60.5±18.1 before CPAP vs 64.2±13.9 ng/ml after CPAP, p = 0.27). Conclusions Plasma Ngal levels were positively associated with the severity of OSA. However, the contribution rate of OSA to systemic Ngal secretion was small and changes in Ngal levels appeared to be influenced largely by other confounding factors. Therefore, it does not seem reasonable to use the Ngal level as a specific biomarker of OSA in clinical practice.
Plasma neutrophil gelatinase associated lipocalin (NGAL) is associated with kidney function in uraemic patients before and after kidney transplantation
Nils E Magnusson, Mads Hornum, Kaj J?rgensen, Jesper Hansen, Claus Bistrup, Bo Feldt-Rasmussen, Allan Flyvbjerg
BMC Nephrology , 2012, DOI: 10.1186/1471-2369-13-8
Abstract: NGAL was measured using a validated in-house Time-Resolved Immuno-flourometric assay (TRIFMA). Repeated measurements differed by < 10% and mean values were used for statistical analyses. Spearman rank order correlation analysis and the Kruskal-Wallis non-parametric test were used to evaluate the association of NGAL concentrations with clinical parameters.Plasma NGAL levels before transplantation in the Tx and uraemic groups were significantly higher than in the healthy controls (1,251 μg/L, 1,478 μg/L vs. 163 μg/L, p < 0.0001). In the Tx group NGAL concentrations were associated with serum creatinine (R = 0.51, p < 0.0001), duration of end-stage renal failure (R = 0.41, p = 0.002) and leukocyte count (R = 0.29, p < 0.026). At 3 and 12 months plasma NGAL concentrations declined to 223 μg/L and 243 μg/L, respectively and were associated with homocysteine (R = 0.39, p = 0.0051 and R = 0.47, p = 0.0007).Plasma NGAL is a novel marker of kidney function, which correlates to duration of end-stage renal failure (ESRD) and serum creatinine in uraemic patients awaiting kidney transplantation. Plasma NGAL is associated with homocysteine in transplanted patients. The prognostic value of these findings requires further studies.Neutrophil gelatinase associated lipocalin (NGAL) also known as Lipocalin 2 or Lcn2 is a 25 kDa protein identified originally as a protein associated with matrix metalloproteinase 9 (MMP-9) of human neutrophils [1]. Lipocalins are extracellular proteins which share a common tertiary structure that forms a barrel-like hydrophobic ligand binding site [2]. When bound to MMP-9, NGAL protects it from proteolytic degradation sustaining the proteolytic activity of MMP-9. No specific receptor for NGAL has yet been identified. However, the endocytosis low density lipoprotein receptor Megalin has been shown to bind NGAL with high affinity suggesting that NGAL is taken up by host cells [3]. NGAL has been suggested as a bacteriostatic agent indicating involvement of N
Urinary Neutrophil Gelatinase-Associated Lipocalin Is a Potential Biomarker for Renal Damage in Patients with Systemic Lupus Erythematosus
Chun-Chen Yang,Song-Chou Hsieh,Ko-Jen Li,Cheng-Han Wu,Ming-Chi Lu,Chang-Youh Tsai,Chia-Li Yu
Journal of Biomedicine and Biotechnology , 2012, DOI: 10.1155/2012/759313
Abstract: Neutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated to be a novel biomarker in acute and chronic kidney disease. We hypothesized that 24-hour urinary NGAL excretion may be a predictor for renal damage in patients with systemic lupus erythematosus (SLE). Thirty-four SLE patients with renal involvement (SLE-renal group), 8 SLE patients without renal involvement (SLE-nonrenal group), 14 patients with non-SLE autoimmune diseases (disease control or DC group), and 12 healthy volunteers (normal control or NC group) were compared for 24-hour urinary excretion of NGAL and different cytokines. We found that the 24-hour urinary NGAL excretion in the SLE-renal group was higher than that in the SLE-non-renal, DC, and NC groups. However, the excretion of interleukin-10, transforming growth factor-1, and tumor necrosis factor- was not different between the SLE-renal and SLE-non-renal groups. Furthermore, NGAL excretion in the SLE-renal group was correlated with serum creatinine levels and creatinine clearance, but not with the SLE Disease Activity Index score. Multivariate logistic regression analysis and receiver operating characteristic curve analysis revealed that 24-hour urinary NGAL excretion is a potential biomarker for renal damage in SLE patients, with higher sensitivity and specificity than anti-dsDNA antibody titers.
Serum Neutrophil Gelatinase-associated Lipocalin as a Predictor of Acute Kidney Injury in Critically-ill Neonates
O.G. El-Farghali,N.M. El-Raggal,N.H. Mahmoud,G.A. Zaina
Pakistan Journal of Biological Sciences , 2012,
Abstract: Early detection of evolving Acute Kidney Injury (AKI) in critically ill neonates can lead to better preventive and therapeutic interventions. Neutrophil Gelatinase-associated Lipocalin (NGAL) is a promising biomarker of AKI, which was also shown to increase in inflammation. The objective of this study was to assess the utility of serum NGAL (sNGAL) as an early marker of evolving AKI in critically-ill neonates with and without sepsis. sNGAL levels were estimated in 60 critically-ill neonates at the time of admission to Neonatal Intensive Care Unit (NICU), in comparison to 20 healthy matched control. Patients were categorized as sepsis (n = 35) and no-sepsis (n = 25) subgroups on basis of clinical and laboratory criteria. They were subsequently discriminated according to creatinine and urine output criteria of the Acute Kidney Injury Network (AKIN), into AKI (n = 34) and no-AKI (n = 26) subgroups. sNGAL levels were significantly higher in the patient group as compared to control (132.7±67.8 vs. 55±10.3 ng mL-1, p = 0.0001). Elevated levels were comparable between sepsis and no-sepsis groups (130.1±69.4 vs. 136.5±66.6 ng mL-1, p = 0.7) and they positively correlated with 48-hour post-admission serum creatinine (p = 0.0001). Patients of AKI group had significantly higher sNGAL than those of no-AKI group (176.2±55.9 vs. 75.9±28.3 ng mL-1, p = 0.0001). A cut-off value for sNGAL of 117.5 ng mL-1, was predictive of AKI with a sensitivity of 82% and a specificity of 88.5%. It could be speculated that measurement of serum NGAL can serve as a clinically useful marker for early prediction of evolving AKI in critically-ill neonates with and without sepsis.
Serum neutrophil gelatinase-B associated lipocalin (NGAL) levels in Down’s syndrome patients  [cached]
Dogliotti Giada,Galliera Emanuela,Licastro Federico,Porcellini Elisa
Immunity & Ageing , 2010, DOI: 10.1186/1742-4933-7-s1-s7
Abstract: Neutrophil gelatinase-associated lipocalin (NGAL) is a group of proteins with different functions. NGAL is released by different cell types such as epithelial cell, hepatocytes and renal tubular cells during inflammation and after cell injury. Expression of NGAL is induced under various pathophysiological conditions such as infection, cancer, inflammation, kidney injury, cardiovascular disease, burn injury, and intoxication, which has an important anti-apoptotic and anti-inflammatory role. Subjects with Down’s syndrome (DS) are affected by many pathological age related conditions such as mental retardation, Alzheimer’s disease, immune defects and increased susceptibility to infections. The aim of this study is to evaluate possible use of NGAL as a marker of inflammatory status for allow an early diagnosis of inflammatory disease such as autoimmune disease in DS patients, that are more susceptible to these pathologies, especially in elderly subjects. In this study were recruited 3 groups of DS subjects (children, adults and elderly) and compared them to healthy control group. The molecules of interest was determinated by immuno-enzymatic assay (ELISA). Our results show that NGAL plasmatic level was significantly higher in DS patients compared to healthy controls. Moreover NGAL levels increase in correlation with the age, and showed a significantly correlation between the increase with the severity of disease. DS is characterized by an enhancement of gene production such as GART, SOD-1 and CBS that encode specific protein and enzyme involved in hydrogen peroxide and superoxide production, species highly cytotoxic implicated in inflammation and ageing. NGAL may have the potential application to ameliorate the toxicity induced by oxidative stress conditions such as Alzheimer’s disease, thalassemia, cardiovascular disease, burn injury, transplantation, diabetes, and aging.
Neutrophil gelatinase-associated lipocalin levels in right and left heart failure: an observational study  [cached]
Fatih Koca,?brahim Halil Tanbo?a,Mehmet Mustafa Can,Alper ?zkan
Anadolu Kardiyoloji Dergisi , 2011,
Abstract: Objective: Neutrophil gelatinase-associated lipocalin (NGAL) is a novel marker for early detection of renotubular deterioration. Despite the limited data concerning the NGAL in heart failure (HF), significance of NGAL in right-sided HF remains unknown. We assessed serum and urinary NGAL in left and right-sided HF due to non-ischemic cardiomyopathy (NICMP) and severe pulmonary arterial hypertension (PAH). Methods: In this cross-sectional observational study, we compared three groups; 35 patients with NICMP, 28 patients with PAH and 27 healthy controls. None had a serum creatinine ≥1.5 mg/dL. Plasma brain natriuretic peptide (BNP) levels, estimated glomerular filtration rate (eGFR) by Cockroft-Gault (CG) and Modification of Diet in Renal Disease Study formulas, echocardiographic measures of left and right ventricles (LV, RV) and non-invasive measurement of cardiac index (CI) by echocardiography and impedance cardiography were assessed. Differences among the groups for continuous variables were evaluated by the ANOVA and the Kruskal-Wallis test as appropriate. The Chi-square test was used for comparison of categorical variables.Results: Despite eGFR with CG formula was lower in NICMP and PAH subsets as compared to those in controls (102±27 and 99.4±29.4 vs 122.4±25.9 mL/min, p<0.05 and p<0.005 in order), serum NGAL [141 (113-151), 174 (130-192) and 132 (95-181) ng/mL] and urinary NGAL [15 (12-18), 15 (12-22) and 13 (8-18) ng/mL] levels were not different among groups (p=0.15 and p=0.35, respectively). Conclusion: Despite the mildly impaired eGFR in left-sided HF due to NICMP and right-sided HF due to PAH, neither serum, nor urinary NGAL levels are elevated in these patients.
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