Vanillin mitigates the adverse impact of cisplatin and methotrexate on rat kidneys

2017 ◽  
Vol 37 (9) ◽  
pp. 937-943 ◽  
Author(s):  
AA Fouad ◽  
WN Al-Melhim
Keyword(s):  
Fas Ligand ◽  
Nitrosative Stress ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Nuclear Factor Κb ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Total Antioxidant ◽  
Factor Α ◽  
Neutrophil Gelatinase ◽  
Rat Kidneys

The present study investigated the probable protective effect of vanillin (VLN) against kidney injury induced by cisplatin (CSN) and methotrexate (MTX) in rats. The rats received a single injection of either CSN (7.5 mg/kg, i.p.) or MTX (20 mg/kg, i.p.). VLN treatment (150 mg/kg/day, i.p.) was started 1 day before administration of the nephrotoxic agents and continued for 7 days. Both CSN and MTX significantly increased serum creatinine, cystatin C, and neutrophil gelatinase–associated lipocalin and kidney tissue renal malondialdehyde, inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-18, nuclear factor-κB p65, cytosolic cytochrome C, and caspase-3 and significantly decreased renal total antioxidant capacity and Bcl-2/Bax ratio in rats. VLN significantly ameliorated the changes of biochemical parameters induced by CSN and MTX. VLN also significantly reduced CSN- and MTX-induced histopathological injury and the expression of Fas ligand in rat kidneys. In conclusion, VLN significantly protected against CSN- and MTX-induced kidney injury in rats by inhibiting oxidative/nitrosative stress, inflammation, and apoptosis.

scholarly journals Effect of Polyethylene-glycolated Carboxyhemoglobin on Renal Microcirculation in a Rat Model of Hemorrhagic Shock

2019 ◽  
Vol 131 (5) ◽  
pp. 1110-1124 ◽  
Author(s):  
Philippe Guerci ◽  
Bulent Ergin ◽  
Aysegul Kapucu ◽  
Matthias P. Hilty ◽  
Ronald Jubin ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Hydroxyethyl Starch ◽  
Kidney Injury ◽  
Mean Difference ◽  
Heme Oxygenase 1 ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Rank Difference ◽  
Factor Α ◽  
Neutrophil Gelatinase ◽  
Necrosis Factor

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Primary resuscitation fluid to treat hemorrhagic shock remains controversial. Use of hydroxyethyl starches raised concerns of acute kidney injury. Polyethylene-glycolated carboxyhemoglobin, which has carbon monoxide–releasing molecules and oxygen-carrying properties, was hypothesized to sustain cortical renal microcirculatory Po2 after hemorrhagic shock and reduce kidney injury. Methods Anesthetized and ventilated rats (n = 42) were subjected to pressure-controlled hemorrhagic shock for 1 h. Renal cortical Po2 was measured in exposed kidneys using a phosphorescence quenching method. Rats were randomly assigned to six groups: polyethylene-glycolated carboxyhemoglobin 320 mg · kg−1, 6% hydroxyethyl starch (130/0.4) in Ringer’s acetate, blood retransfusion, diluted blood retransfusion (~4 g · dl−1), nonresuscitated animals, and time control. Nitric oxide and heme oxygenase 1 levels were determined in plasma. Kidney immunohistochemistry (histologic scores of neutrophil gelatinase-associated lipocalin and tumor necrosis factor-α) and tubular histologic damages analyses were performed. Results Blood and diluted blood restored renal Po2 to 51 ± 5 mmHg (mean difference, −18; 95% CI, −26 to −11; P < 0.0001) and 47 ± 5 mmHg (mean difference, −23; 95% CI, −31 to −15; P < 0.0001), respectively, compared with 29 ± 8 mmHg for hydroxyethyl starch. No differences between polyethylene-glycolated carboxyhemoglobin and hydroxyethyl starch were observed (33 ± 7 mmHg vs. 29 ± 8 mmHg; mean difference, −5; 95% CI, −12 to 3; P = 0.387), but significantly less volume was administered (4.5 [3.3–6.2] vs. 8.5[7.7–11.4] ml; mean rank difference, 11.98; P = 0.387). Blood and diluted blood increased the plasma bioavailability of nitric oxide compared with hydroxyethyl starch (mean rank difference, −20.97; P = 0.004; and −17.13; P = 0.029, respectively). No changes in heme oxygenase 1 levels were observed. Polyethylene-glycolated carboxyhemoglobin limited tubular histologic damages compared with hydroxyethyl starch (mean rank difference, 60.12; P = 0.0012) with reduced neutrophil gelatinase-associated lipocalin (mean rank difference, 84.43; P < 0.0001) and tumor necrosis factor-α (mean rank difference, 49.67; P = 0.026) histologic scores. Conclusions Polyethylene-glycolated carboxyhemoglobin resuscitation did not improve renal Po2 but limited tubular histologic damages and neutrophil gelatinase-associated lipocalin upregulation after hemorrhage compared with hydroxyethyl starch, whereas a lower volume was required to sustain macrocirculation.

scholarly journals Ventilator-induced lung injury increases expression of endothelial inflammatory mediators in the kidney

2017 ◽  
Vol 312 (4) ◽  
pp. F654-F660 ◽  
Author(s):  
Mark Hepokoski ◽  
Joshua A. Englert ◽  
Rebecca M. Baron ◽  
Laura E. Crotty-Alexander ◽  
Mark M. Fuster ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Inflammatory Mediators ◽  
Cecal Ligation ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Ventilator Induced Lung Injury ◽  
Angiopoietin 2 ◽  
Neutrophil Gelatinase

In critical illness, such as sepsis or the acute respiratory distress syndrome, acute kidney injury (AKI) is common and associated with increased morbidity and mortality. Mechanical ventilation in critical illnesses is also a risk factor for AKI, but it is potentially modifiable. Injurious ventilation strategies may lead to the systemic release of inflammatory mediators from the lung due to ventilator induced lung injury (VILI). The systemic consequences of VILI are difficult to differentiate clinically from other systemic inflammatory syndromes, such as sepsis. The purpose of this study was to identify unique changes in the expression of inflammatory mediators in kidney tissue in response to VILI compared with systemic sepsis to gain insight into direct effects of VILI on the kidney. Four groups of mice were compared—mice with sepsis from cecal ligation and puncture (CLP), mice subjected to injurious mechanical ventilation with high tidal volumes (VILI), mice exposed to CLP followed by VILI (CLP+VILI), and sham controls. Protein expression of common inflammatory mediators in kidneys was analyzed using a proteome array and confirmed by Western blot analysis or ELISA. VEGF and VCAM-1 were found to be significantly elevated in kidneys from VILI mice compared with sham and CLP. Angiopoietin-2 was significantly increased in CLP+VILI compared with CLP alone and was also correlated with higher levels of AKI biomarker, neutrophil gelatinase-associated lipocalin. These results suggest that VILI alters the renal expression of VEGF, VCAM-1, and angiopoietin-2, and these proteins warrant further investigation as potential biomarkers and therapeutic targets.

scholarly journals Screening of early diagnostic markers of gentamicin-induced acute kidney injury in canines

2019 ◽  
Vol 63 (3) ◽  
pp. 405-411
Author(s):  
Jia-San Zheng ◽  
Jing-Nie ◽  
Ting-Ting Zhu ◽  
Hong-Ri Ruan ◽  
Xue-Wei ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Characteristic Curve ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Fatty Acid Binding ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Transmission Electron ◽  
Renal Tubular ◽  
Kidney Injury Molecule 1 ◽  
Neutrophil Gelatinase

Abstract Introduction The value of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), and liver-type fatty acid binding protein (L-FABP) was assessed in early diagnosis of gentamicin-induced acute kidney injury (AKI) in dogs. Material and Methods Subcutaneous gentamicin injection in 16 healthy adult beagles made the AKI model. Blood was sampled every 6 h to detect NGAL, Kim-1, L-FABP, and serum creatinine (SCr) concentrations. Kidney tissue of two dogs was taken before the injection, as soon as SCr was elevated (78 μmol/L), and when it had risen to 1.5 times the baseline, and haematoxylin-eosin staining and transmission electron microscopy (TEM) were used to observe changes. Results NGAL, Kim-1, and SCr levels were significantly increased (P < 0.05) at 18, 30, and 78 h post injection, but L-FABP concentration was not associated with renal injury. At the earliest SCr elevation stage, findings were mild oedema, degeneration, and vacuolisation in renal tubular epithelial cells in pathology, and mild cytoplasmic and mitochondrial oedema in TEM. At this time point, NGAL and Kim-1 concentrations were significantly increased (P < 0.05), indicating that these two molecules biomark early kidney injury in dogs. Using receiver operating characteristic curve analysis, their warning levels were > 25.31 ng/mL and > 48.52 pg/mL. Conclusion Plasma NGAL and Kim-1 above warning levels are early indicators of gentamicin-induced AKI in dogs.

scholarly journals Comparison of urine neutrophil gelatinase-associated lipocalin to serum creatinine to assess kidney function in neonatal asphyxia

2017 ◽  
Vol 56 (6) ◽  
pp. 356 ◽  
Author(s):  
Winston Leonardo Tanzil ◽  
Rocky Wilar ◽  
Max Frans Josef Mantik ◽  
Adrian Umboh ◽  
Suryadi Nicolaas Napoleon Tatura
Keyword(s):  
Serum Creatinine ◽  
Kidney Function ◽  
Predictive Value ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Urinary Ngal ◽  
Cross Sectional ◽  
Neonatal Asphyxia ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Neutrophil Gelatinase

Background Infants with neonatal asphyxia have multiorgan damage, such as to the kidneys (50%), central nervous system (28%), cardiovascular system (25%), and lungs (23%). Neonatal asphyxia reduces kidney perfusion, often leading to acute kidney injury (AKI) after asphyxia. Neutrophil gelatinase-associated lipocalin (NGAL) levels in the blood, urine and kidney tissue increased rapidly in AKI. Urinary NGAL is proposed to have better performance in diagnosing AKI than creatinine due to its earlier, rapid level increase and it is less invasive.Objective To compare urinary NGAL to serum creatinine as a marker to assess kidney function in neonatal asphyxia.Methods Diagnostic comparison study with cross-sectional design was performed at neonatal intensive care unit (NICU) of Prof. Dr. R. D. Kandou Hospital, Manado from November 2015 to February 2016. All subjects had neonatal asphyxia. Data were analyzed using descriptive analysis, receiver-operator characteristic (ROC) curve, and Z-test.Results Urinary NGAL with cut-off point of 652.24 ng/mL can predict AKI in neonates with asphyxia with 100% sensitivity, 75% specificity, 52.3% positive predictive value, and 100% negative predictive value. Chi-square test resulted in a value of x2 = 20.036, P=0.0001).This shows that urinary NGAL levels >652,24 ng/mL can predicts AKI by 20 times in infants with neonatal asphyxia. So, urinary NGAL performs better than serum creatinine, therefore it can replace serum creatinine as an alternative non-invasive diagnostic test for diagnosing AKI in infants with neonatal asphyxia.Conclusion The diagnostic value of urinary NGAL is higher than that of serum creatinine in assessing kidney function in neonatal asphyxia. 

scholarly journals Crucial roles of binding sites for NF-κB and C/EBPs in IκB-ζ-mediated transcriptional activation

2007 ◽  
Vol 405 (3) ◽  
pp. 605-615 ◽  
Author(s):  
Susumu Matsuo ◽  
Soh Yamazaki ◽  
Koichiro Takeshige ◽  
Tatsushi Muta
Keyword(s):  
Binding Site ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Interleukin 1 ◽  
Nuclear Factor Κb ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Il Interleukin ◽  
Factor Α ◽  
Neutrophil Gelatinase ◽  
Stimulation Of

IκB-ζ [inhibitor of NF-κB (nuclear factor κB) ζ] is a nuclear protein that is induced upon stimulation of TLRs (Toll-like receptors) and IL (interleukin)-1 receptor. IκB-ζ harbours C-terminal ankyrin repeats that interact with NF-κB. Our recent studies have shown that, upon stimulation, IκB-ζ is essential for the induction of a subset of inflammatory genes, represented by IL-6, whereas it inhibits the expression of TNF (tumour necrosis factor)-α. In the present study, we investigated mechanisms that determine the different functions of IκB-ζ. We found that co-expression of IκB-ζ and the NF-κB subunits synergistically activates transcription of the hBD-2 (human β-defensin 2) and NGAL (neutrophil gelatinase-associated lipocalin) genes, whereas it inhibits transcription of E-selectin. Reporter analyses indicated that, in addition to an NF-κB-binding site, a flanking C/EBP (CCAAT/enhancer-binding protein)-binding site in the promoters is essential for the IκB-ζ-mediated transcriptional activation. Using an artificial promoter consisting of the NF-κB- and C/EBP-binding sites, transcriptional activation was observed upon co-transfection with IκB-ζ and NF-κB, indicating that these sequences are minimal elements that confer the IκB-ζ-mediated transcriptional activation. Chromatin immunoprecipitation assays and knockdown experiments showed that both IκB-ζ and the NF-κB subunits were recruited to the NGAL promoter and were essential for the transcriptional activation of the hBD-2 and NGAL promoters on stimulation with IL-1β. The activation of the NGAL promoter by transfection of IκB-ζ and NF-κB was suppressed in C/EBPβ-depleted cells. Thus IκB-ζ acts as an essential transcriptional activator by forming a complex with NF-κB on promoters harbouring the NF-κB- and C/EBP-binding sites, upon stimulation of TLRs or IL-1 receptor.

Sign in / Sign up

Export Citation Format

Share Document