scholarly journals 15-Deoxy-Δ12,14-prostaglandin J2Exerts Antioxidant Effects While Exacerbating Inflammation in Mice Subjected to Ureteral Obstruction

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Line Nilsson ◽  
Fredrik Palm ◽  
Rikke Nørregaard
Keyword(s):  
Oxidative Stress ◽  
Ureteral Obstruction ◽  
Kidney Injury ◽  
Oxidative Stress Marker ◽  
Obstructive Nephropathy ◽  
Heme Oxygenase 1 ◽  
Downstream Target ◽  
High Concentrations ◽  
Kidney Injury Molecule 1 ◽  
And Oxidative Stress

Urinary obstruction is associated with inflammation and oxidative stress, leading to renal dysfunction. Previous studies have shown that 15-deoxy-Δ12,14-prostaglandin J2(15d-PGJ2) has both antioxidant and anti-inflammatory effects. Using a unilateral ureteral obstruction (UUO) mouse model, we examined the effects of 15d-PGJ2on oxidative stress and inflammation in the kidney. Mice were subjected to UUO for 3 days and treated with 15d-PGJ2. Protein and RNA expression were examined using immunoblotting and qPCR. 15d-PGJ2increased NF-E2-related nuclear factor erythroid-2 (Nrf2) protein expression in response to UUO, and heme oxygenase 1 (HO-1), a downstream target of Nrf2, was induced by 15d-PGJ2. Additionally, 15d-PGJ2prevented protein carbonylation, a UUO-induced oxidative stress marker. Inflammation, measured by nuclear NF-κB, F4/80, and MCP-1, was increased in response to UUO and further increased by 15d-PGJ2. Renal injury was aggravated by 15d-PGJ2treatment as measured by kidney injury molecule-1 (KIM-1) and cortical caspase 3 content. No effect of 15d-PGJ2was observed on renal function in mice subjected to UUO. This study illustrates differentiated functioning of 15d-PGJ2on inflammation and oxidative stress in response to obstructive nephropathy. High concentrations of 15d-PGJ2protects against oxidative stress during 3-day UUO in mice; however, it aggravates the associated inflammation.

scholarly journals Neonatal obstructive nephropathy induces necroptosis and necroinflammation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bastian Popper ◽  
Marian Theodor Rammer ◽  
Mojca Gasparitsch ◽  
Teresa Singer ◽  
Ursula Keller ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Kidney Development ◽  
Urinary Tract Obstruction ◽  
Kidney Injury ◽  
Kinase Domain ◽  
Obstructive Nephropathy ◽  
Tubular Necrosis ◽  
Basement Membrane Thickening ◽  
Tnf Α ◽  
Kidney Injury Molecule 1

AbstractUrinary tract obstruction during kidney development causes tubular apoptosis, tubular necrosis, and interstitial inflammation. Necroptosis is a subtype of programmed necrosis mediated by the receptor-interacting serine/threonine-protein kinase-3 (RIPK3) and the pseudokinase mixed lineage kinase domain-like (MLKL). Necrosis induces inflammation and stimulates cell death in an autoamplification loop named necroinflammation. Here, we studied necroptosis and necroinflammation in obstructive nephropathy induced by unilateral ureteral obstruction (UUO) in neonatal C57Bl/6J mice. Ureteral obstruction induced tubular dilatation, tubular basement membrane thickening, cast formation, and increased expression of kidney injury molecule-1 (KIM-1). Morphological investigations showed either apoptotic or necrotic cells in the tubular compartment. Biochemical analysis revealed increased caspase-8 activity and upregulation of RIPK3 as well as phosphorylated-MLKL in UUO-kidneys. Pro-inflammatory cytokines (IL-1α, INF-γ, TNF-α) were upregulated following UUO. Taken together we show that necroptosis and necroinflammation are accompanied phenomena in neonatal kidneys with obstruction. These findings may help to develop novel strategies to treat congenital obstructive nephropathy.

scholarly journals Formononetin Upregulates Nrf2/HO-1 Signaling and Prevents Oxidative Stress, Inflammation, and Kidney Injury in Methotrexate-Induced Rats

Antioxidants ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 430 ◽  
Author(s):  
Saleem H. Aladaileh ◽  
Omnia E. Hussein ◽  
Mohammad H. Abukhalil ◽  
Sultan A. M. Saghir ◽  
May Bin-Jumah ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Antioxidant Defenses ◽  
Heme Oxygenase 1 ◽  
Caspase 9 ◽  
Tnf Α ◽  
Cox 2 ◽  
Kidney Injury Molecule 1

Acute kidney injury (AKI) is a serious complication of methotrexate (MTX). This study explored the protective effect of the isoflavone formononetin (FN) against MTX nephrotoxicity with an emphasis on oxidative stress, inflammation, and nuclear factor (erythroid-derived 2)-like 2/heme oxygenase 1 (Nrf2/HO-1) signaling. Rats received FN (10, 20, and 40 mg/kg) for 10 days and a single dose of MTX on day 7. MTX induced kidney injury was characterized by increased serum creatinine and urea, kidney injury molecule-1 (Kim-1), and several histological alterations. FN ameliorated kidney function and inhibited the renal tissue injury induced by MTX. Reactive oxygen species (ROS), lipid peroxidation (LPO), nitric oxide, and 8-Oxo-2′-deoxyguanosine were increased, whereas antioxidant defenses were diminished in the kidney of MTX-administered rats. In addition, MTX upregulated renal iNOS, COX-2, TNF-α, IL-1β, Bax, caspase-9, and caspase-3, and decreased Bcl-2, Nrf2, and HO-1. FN suppressed oxidative stress, LPO, DNA damage, iNOS, COX-2, proinflammatory cytokines, and apoptosis, and boosted Bcl-2, antioxidants, and Nrf2/HO-1 signaling in MTX-administered rats. In conclusion, FN prevents MTX-induced AKI by activating Nrf2/HO-1 signaling and attenuates oxidative damage and inflammation. Thus, FN may represent an effective adjuvant that can prevent MTX nephrotoxicity, pending further mechanistic studies.

scholarly journals Disruption of cyclooxygenase type 2 exacerbates apoptosis and renal damage during obstructive nephropathy

2015 ◽  
Vol 309 (12) ◽  
pp. F1035-F1048 ◽  
Author(s):  
Line Nilsson ◽  
Kirsten Madsen ◽  
Søren Krag ◽  
Jørgen Frøkiær ◽  
Boye L. Jensen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Heme Oxygenase ◽  
Ureteral Obstruction ◽  
Obstructive Nephropathy ◽  
Heme Oxygenase 1 ◽  
Oxidative Stress Markers ◽  
Tubular Injury ◽  
Stress Markers ◽  
Cox 2

Renal oxidative stress is increased in response to ureteral obstruction. In vitro, cyclooxygenase (COX)-2 activity contributes to protection against oxidants. In the present study, we tested the hypothesis that COX-2 activity counters oxidative stress and apoptosis in an in vivo model of obstructive nephropathy. Renal oxidative stress markers, antioxidant enzymes, and markers of tubular injury, tubular dilation, and apoptosis were investigated in COX-2 knockout (COX-2−/−) and wild-type (WT) mice subjected to 3 or 7 days of unilateral ureteral obstruction (UUO). In a separate series, WT sham-operated and UUO mice were treated with a selective COX-2 inhibitor, parecoxib. COX-2 increased in response to UUO; the oxidative stress markers 4-hydroxynonenal and nitrotyrosine protein residues increased in kidney tissue with no genotype difference after UUO, whereas the antioxidant enzymes heme oxygenase-1 and SOD2 displayed higher levels in COX-2−/− mice. Tubular injury was aggravated by COX-2 deletion, as measured by tubular dilatation, an increase in kidney injury molecule-1, cortical caspase-3 content, and apoptosis index. In conclusion, COX-2 is necessary to protect against tubular injury and apoptosis after UUO but not necessary to protect against oxidative stress. COX-2 is not likely to directly regulate antioxidant enzymes heme oxygenase-1 and SOD in the kidney.

scholarly journals Angelica sinensis has inherent endothelial cell toxicity at high concentrations but can also protect the vascular endothelium from oxidative stress-induced injury at moderate concentrations

2011 ◽  
Vol 1 (1) ◽  
pp. 8
Author(s):  
Miko Yamada ◽  
Betty Pat ◽  
Glenda Gobe ◽  
Ken Wojcikowski
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Heme Oxygenase ◽  
Angelica Sinensis ◽  
Molecular Characteristics ◽  
Heme Oxygenase 1 ◽  
High Concentrations ◽  
Induced Apoptosis ◽  
And Oxidative Stress

Hypoxia and oxidative stress are important factors in the pathogenesis of many acute forms of injury, especially acute kidney injury. Apoptosis is a key mode of endothelial cell death from oxidative stress. Minimising the detrimental effects of oxidative stress is necessary to reduce injury, and new treatment strategies are constantly being sought. The aim of this study was to investigate the ability of an aqueous/methanol extract of Angelica sinensis (AS) root (Chinese names Danggui, Dong quai, Donggui) to protect endothelium from hypoxia and oxidative stress. This was compared in specialised kidney endothelium (renal medullary vascular endothelial cells; RMVEC) versus central endothelium (aortic endothelial cells; AEC). Toxicity of various strengths of AS was first tested in RMVEC and AEC using % apoptosis and mitosis as outcomes. Morphological and molecular characteristics of apoptosis and mitosis, and the effect of AS on heme-oxygenase-1, a marker of cellular response to oxidative stress, were also investigated. The results showed that, at concentrations of 2500µg/mL or greater, AS significantly increased apoptosis in RMVEC and AEC (P<0.05), however concentrations of 2000 µg/mL or less were non-toxic and also non-mitogenic. Endothelial cells were then treated with hydrogen peroxide (0.8 mM for RMVEC; 0.6 mM for AEC) for oxidative stress, with and without 2000 µg/mL AS. AS significantly inhibited oxidant-induced apoptosis (P<0.05) but had little effect on mitosis. AS also increased heme-oxygenase-1, but only in AEC. AS extracts may have some inherent toxicity at high concentrations, but with careful analysis of non-toxic levels, both renal and central endothelium benefited from AS against oxidative stress-induced apoptosis, without inducing excessive mitosis, and AS may find application in some oxidant-induced disease.

Targeting Inflammation and Oxidative Stress as a Therapy for Ischemic Kidney Injury

2020 ◽  
Vol 85 (12-13) ◽  
pp. 1591-1602
Author(s):  
N. V. Andrianova ◽  
D. B. Zorov ◽  
E. Y. Plotnikov
Keyword(s):  
Oxidative Stress ◽  
Kidney Injury ◽  
And Oxidative Stress

scholarly journals Protective Effects of Taurine Chloramine on Experimentally Induced Colitis: NFκB, STAT3, and Nrf2 as Potential Targets

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 479
Author(s):  
Seong Hoon Kim ◽  
Hye-Won Yum ◽  
Seung Hyeon Kim ◽  
Wonki Kim ◽  
Su-Jung Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Parent Compound ◽  
Oxidative Stress Marker ◽  
Heme Oxygenase 1 ◽  
Trinitrobenzene Sulfonic Acid ◽  
Protective Effects ◽  
Taurine Chloramine ◽  
Proinflammatory Mediators ◽  
Experimentally Induced

Taurine chloramine (TauCl) is an endogenous anti-inflammatory substance which is derived from taurine, a semi-essential sulfur-containing β-amino acid found in some foods including meat, fish, eggs and milk. In general, TauCl as well as its parent compound taurine downregulates production of tissue-damaging proinflammatory mediators, such as chemokines and cytokines in many different types of cells. In the present study, we investigated the protective effects of TauCl on experimentally induced colon inflammation. Oral administration of TauCl protected against mouse colitis caused by 2,4,6-trinitrobenzene sulfonic acid (TNBS). TauCl administration attenuated apoptosis in the colonic mucosa of TNBS-treated mice. This was accompanied by reduced expression of an oxidative stress marker, 4-hydroxy-2-nonenal and proinflammatory molecules including tumor necrosis factor-α, interleukin-6 and cyclooxygenase-2 in mouse colon. TauCl also inhibited activation of NFκB and STAT3, two key transcription factors mediating proinflammatory signaling. Notably, the protective effect of TauCl on oxidative stress and inflammation in the colon of TNBS-treated mice was associated with elevated activation of Nrf2 and upregulation of its target genes encoding heme oxygenase-1, NAD(P)H:quinone oxidoreductase, glutamate cysteine ligase catalytic subunit, and glutathione S-transferase. Taken together, these results suggest that TauCl exerts the protective effect against colitis through upregulation of Nrf2-dependent cytoprotective gene expression while blocking the proinflammatory signaling mediated by NFκB and STAT3.

scholarly journals Maternal Urinary Metal and Metalloid Concentrations in Association with Oxidative Stress Biomarkers

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 114
Author(s):  
Pahriya Ashrap ◽  
Deborah J. Watkins ◽  
Ginger L. Milne ◽  
Kelly K. Ferguson ◽  
Rita Loch-Caruso ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prostaglandin F2α ◽  
Urine Samples ◽  
Oxidative Stress Marker ◽  
Essential Metals ◽  
Male Fetus ◽  
Metal Concentrations ◽  
Fetal Sex ◽  
Wide Range ◽  
And Oxidative Stress

Metal exposure has been associated with a wide range of adverse birth outcomes and oxidative stress is a leading hypothesis of the mechanism of action of metal toxicity. We assessed the relationship between maternal exposure to essential and non-essential metals and metalloids in pregnancy and oxidative stress markers, and sought to identify windows of vulnerability and effect modification by fetal sex. In our analysis of 215 women from the PROTECT birth cohort study, we measured 14 essential and non-essential metals in urine samples at three time points during pregnancy. The oxidative stress marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite 2,3-dinor-5,6-dihydro-15-15-F2t-IsoP, as well as prostaglandin F2α (PGF2α), were also measured in the same urine samples. Using linear mixed models, we examined the main effects of metals on markers of oxidative stress as well as the visit-specific and fetal sex-specific effects. After adjustment for covariates, we found that a few urinary metal concentrations, most notably cesium (Cs) and copper (Cu), were associated with higher 8-iso-PGF2α with effect estimates ranging from 7.3 to 14.9% for each interquartile range, increase in the metal concentration. The effect estimates were generally in the same direction at the three visits and a few were significant only among women carrying a male fetus. Our data show that higher urinary metal concentrations were associated with elevated biomarkers of oxidative stress. Our results also indicate a potential vulnerability of women carrying a male fetus.

Daphnetin Ameliorates Corticosterone-Induced Depressive-Like Behavior and Oxidative Stress in Mice Via Nuclear Factor Erythroid 2-Related Factor/Heme Oxygenase-1 Pathway

2021 ◽  
Vol 19 (4) ◽  
pp. 470-476
Author(s):  
Chao Liu ◽  
Chao Liang ◽  
Jie Huang
Keyword(s):  
Oxidative Stress ◽  
Consumption Rate ◽  
Tail Suspension Test ◽  
Protein Carbonyl ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Sucrose Consumption ◽  
Markers Of Oxidative Stress ◽  
Swimming Test ◽  
And Oxidative Stress

We have investigated the effect of daphnetin on depressive-like behavior and oxidative stress caused by corticosterone in mice. To this end, we have analyzed the effect of corticosterone alone and combination of corticosterone and daphnetin on three behavioral indices of depressive-like behavior - sucrose consumption rate, forced swimming test, and tail suspension test as well as biochemical markers of oxidative stress - malondialdehyde, nitrite, protein carbonyl, nonprotein sulfhydryl and glutathione contents as well as hippocampal cell apoptosis. The results support the conclusion that daphnetin diminished corticosterone induced depressive like behavior and oxidative stress by activating Nrf2/HO-1 pathway.

scholarly journals The Protective Effect of Sika Deer Antler Protein on Gentamicin-Induced Nephrotoxicity in Vitro and in Vivo

2018 ◽  
Vol 50 (3) ◽  
pp. 841-850 ◽  
Author(s):  
Hang Sun ◽  
Huihai Yang ◽  
Haonan Ruan ◽  
Wei Li ◽  
Xinhong He ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sika Deer ◽  
Kidney Injury ◽  
Hek293 Cells ◽  
Inflammatory Factors ◽  
Oxidative Stress Marker ◽  
Renal Protection ◽  
Deer Antler

Background/Aims: Sika deer (Cervus nippon Temminck) antler is traditional animal medicine of renal protection in East Asia. This study measured the effect of sika deer antler protein (SDAPR) on gentamicin (GM)-induced cytotoxicity in HEK293 cells, and investigated the effect of SDAPR against GM-induced nephrotoxicity in mice. Methods: HEK293 cells viability and oxidative stress were measured in HEK293 cells while flow cytometry was used for apoptosis analysis. The acute kidney injury biomarkers, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and cystatin c (Cys-C), were repeatedly measured by ELISA assay. ICR male mice were randomly assigned six groups: Control, GM with vehicle, single SDAPR, GM with SDAPR at three concentrations 50, 100, 200 mg/kg/d, p.o., 10 d. GM was injected for 8 consecutive days (100 mg/kg/d, i.p.). Renal function, oxidative stress and levels of inflammatory factors were measured in vivo. Renal tissues were stained with H&E to observe pathological changes. Results: Pretreatment with SDAPR (0.5-4.0 mg/mL) significantly improved cell viability. Treatment with SDAPR could reduce KIM-1, NGAL and Cys-C activity. SDAPR could improve antioxidant defense and attenuated apoptosis on HEK293 cells. SDAPR also ameliorated GM-induced histopathologic changes, and decreased blood urea nitrogen (BUN) and serum creatinine (Cr). Additionally, SDAPR significantly regulated oxidative stress marker and interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) inflammatory cytokines. Conclusion: These results show that SDAPR could be an effective dietary supplement to relieve GM-induced nephrotoxicity by improved antioxidase activity, suppressed inflammation, and inhibited apoptosis in vitro and vivo.

Sign in / Sign up

Export Citation Format

Share Document