Ultrasound Assessment of Inflammation and Renal Tissue Injury With Microbubbles Targeted to P-Selectin

In renal tissue injury, activation of the transcription factor NF-κB has a central role in the induction of proinflammatory gene expression, which are involved in the development of progressive renal inflammatory disease. The function of NF-κB during the switch from the inflammatory process toward resolution, however, is largely unknown. Therefore, we assessed the time-dependent activation and function of NF-κB in two different models of acute nephritis. Our experiments demonstrate a biphasic activation of NF-κB in the anti-Thy-1 model of glomerulonephritis in rats and the LPS-induced nephritis in mice, with a first peak during the induction phase and a second peak during the resolution period. After induction of glomerular immune injury in rats, predominantly NF-κB p65/p50 heterodimer complexes are shifted to the nucleus whereas during the resolution phase predominantly p50 homodimers could be demonstrated in the nuclear compartment. In addition, we could demonstrate that p50 protein plays a pivotal role in the resolution of LPS-induced renal inflammation since NF-κB p50 knockout mice demonstrate significantly higher chemokine expression, prolonged renal inflammatory cell infiltration with consecutive tissue injury, and reduced survival. In conclusion, our studies indicate that NF-κB subunit p50 proteins have critical in vivo functions in immunologically mediated renal disease by downregulating inflammation during the resolution period.

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NADPH Oxidase as a Therapeutic Target for Oxalate Induced Injury in Kidneys

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/462361 ◽

2013 ◽

Vol 2013 ◽

pp. 1-18 ◽

Cited By ~ 34

Author(s):

Sunil Joshi ◽

Ammon B. Peck ◽

Saeed R. Khan

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Tissue Injury ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Reactive Oxygen ◽

Renal Tissue ◽

Oxygen Species ◽

Gene Expressions

A major role of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes is to catalyze the production of superoxides and other reactive oxygen species (ROS). These ROS, in turn, play a key role as messengers in cell signal transduction and cell cycling, but when they are produced in excess they can lead to oxidative stress (OS). Oxidative stress in the kidneys is now considered a major cause of renal injury and inflammation, giving rise to a variety of pathological disorders. In this review, we discuss the putative role of oxalate in producing oxidative stress via the production of reactive oxygen species by isoforms of NADPH oxidases expressed in different cellular locations of the kidneys. Most renal cells produce ROS, and recent data indicate a direct correlation between upregulated gene expressions of NADPH oxidase, ROS, and inflammation. Renal tissue expression of multiple NADPH oxidase isoforms most likely will impact the future use of different antioxidants and NADPH oxidase inhibitors to minimize OS and renal tissue injury in hyperoxaluria-induced kidney stone disease.

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Intrarenal gene expression of proinflammatory chemokines and cytokines in chronic proteinuric glomerulopathies

Physiological Research ◽

10.33549/physiolres.930932 ◽

2007 ◽

pp. 221-226

Author(s):

I Brabcová ◽

K Kotsch ◽

P Hřibová ◽

A Loužecká ◽

K Bartošová ◽

...

Keyword(s):

Mrna Expression ◽

Transforming Growth Factor ◽

Tissue Injury ◽

Renal Tissue ◽

Renal Diseases ◽

Necrosis Factor Alpha ◽

Cytokines And Chemokines ◽

Factor Alpha ◽

Pcr Method ◽

Protein Load

Proteinuria has been recently shown to be an independent risk factor for the progression of chronic nephropathies, but the actual mechanisms by which urinary protein load damages renal tissue in humans remain unsolved. Using real-time RT-PCR method we evaluated intrarenal mRNA expression of various cytokines and chemokines in patients with biopsy-proven IgA nephropathy (IgAN, n=11), membranous nephropathy (MN, n=6) and focal and segmental glomerulosclerosis (FSGS, n=6) who exhibited proteinuria over 0.5 g/day. There was a significant positive correlation between the proteinuria extent and the intrarenal RANTES (regulated upon activation normal T cell expressed and secreted) mRNA expression in patients with IgAN, a similar trend was also observed in patients with MN and FSGS. There were no clear relationships between the proteinuria and intrarenal mRNA expression of tumor necrosis factor alpha, transforming growth factor beta1 and monocyte chemoattractant peptide-1. There were no differences in the pattern of cytokine mRNA expression between different glomerulopathies. In conclusion, our results support the hypothesis that lymphocytes, macrophages and their products provoke tissue injury in response to proteinuria independently of the nature of renal diseases in man.

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1485: The Isolated Dye Perfused Pig Kidney - A Reliable Tissue Model for the Evaluation of Renal Tissue Injury. A Comparison of Two Shockwave Systems

The Journal of Urology ◽

10.1016/s0022-5347(18)38693-2 ◽

2004 ◽

Vol 171 (4S) ◽

pp. 391-391 ◽

Cited By ~ 1

Author(s):

Christian G. Chaussy ◽

Thorsten Bergsdorf ◽

Stefan Thueroff ◽

Christian Chmelar

Keyword(s):

Tissue Injury ◽

Renal Tissue ◽

Tissue Model ◽

Pig Kidney

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Association of a Disrupted Dipping Pattern of Blood Pressure with Progression of Renal Injury during the Development of Salt-Dependent Hypertension in Rats

International Journal of Molecular Sciences ◽

10.3390/ijms21062248 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2248 ◽

Cited By ~ 1

Author(s):

Abu Sufiun ◽

Asadur Rahman ◽

Kazi Rafiq ◽

Yoshihide Fujisawa ◽

Daisuke Nakano ◽

...

Keyword(s):

Blood Pressure ◽

Circadian Rhythm ◽

Renal Injury ◽

Tissue Injury ◽

Renal Tissue ◽

High Salt ◽

Hypertensive Rats ◽

High Salt Diet ◽

Salt Diet ◽

The Difference

The aim of the present study is to investigate whether a disruption of the dipping pattern of blood pressure (BP) is associated with the progression of renal injury in Dahl salt-sensitive (DSS) hypertensive rats. Seven-week-old DSS rats were fed a high salt diet (HSD; 8% NaCl) for 10 weeks, followed by a transition to a normal salt diet (NSD; 0.3% NaCl) for 4 weeks. At baseline, NSD-fed DSS rats showed a dipper-type circadian rhythm of BP. By contrast, HSD for 5 days caused a significant increase in the difference between the active and inactive periods of BP with an extreme dipper type of BP, while proteinuria and renal tissue injury were not observed. Interestingly, HSD feeding for 10 weeks developed hypertension with a non-dipper pattern of BP, which was associated with obvious proteinuria and renal tissue injury. Four weeks after switching to an NSD, BP and proteinuria were significantly decreased, and the BP circadian rhythm returned to the normal dipper pattern. These data suggest that the non-dipper pattern of BP is associated with the progression of renal injury during the development of salt-dependent hypertension.

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Troxerutin down-regulates KIM-1, modulates p38 MAPK signaling, and enhances renal regenerative capacity in a rat model of gentamycin-induced acute kidney injury

Food & Function ◽

10.1039/c8fo01086b ◽

2018 ◽

Vol 9 (12) ◽

pp. 6632-6642 ◽

Cited By ~ 7

Author(s):

Samir A. Salama ◽

Hany H. Arab ◽

Ibrahim A. Maghrabi

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

P38 Mapk ◽

Tissue Regeneration ◽

Rat Model ◽

Tissue Injury ◽

Kidney Injury ◽

Renal Tissue ◽

Mapk Signaling ◽

Regenerative Capacity

Troxerutin enhances renal tissue regeneration, improves renal function, and decreases renal tissue injury in gentamycin-treated rats.

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The role of nitric oxide in iron-induced rat renal injury

Human & Experimental Toxicology ◽

10.1191/0960327104ht485oa ◽

2004 ◽

Vol 23 (11) ◽

pp. 533-536 ◽

Cited By ~ 11

Author(s):

M Kadkhodaee ◽

A Gol

Keyword(s):

Nitric Oxide ◽

Renal Function ◽

Vitamin E ◽

Renal Injury ◽

Tissue Injury ◽

Renal Tissue ◽

No Synthase ◽

Plasma Vitamin ◽

Anti Oxidant ◽

Plasma Vitamin E

Iron overload and enhanced hydroxyl radical (•OH) formation have been implicated as the causative factors of oxidative stress in different organs. Both pro-oxidant and anti-oxidant properties have been reported for nitric oxide (NO) in iron-mediated tissue injury. To determine the contribution of NO to iron-induced renal injury, eight groups of rats (eight in each group) were studied as follows: control (normal saline), L-Arg (L-arginine as a substrate of NO synthase, 400 mg/kg), L-NAME (an inhibitor of NO synthase, 8 mg/kg), Fe (iron dextran, 600 mg/kg), DFO (deferroxamine as a chelator of iron, 150 mg/kg), Fe+L-Arg, Fe+L-NAME, DFO+L-Arg. Twenty-four hours after the injections, blood samples were taken and kidneys removed for biochemical analysis. Plasma creatinine and urea were used to stimulate renal function. Renal tissue and plasma vitamin E levels, the most important endogenous fat soluble antioxidant, were measured by HPLC and UV detection. In this study, renal function was markedly reduced in the Fe group compared to controls (creatinine, 1.02± 0.05 mg/dL versus 0.78±0.04 P <0.05; urea, 49.59±1.69 mg/dL versus 40.75±0.86, P <0.01). Vitamin E levels were significantly lower in the Fe group compared to controls (plasma P <0.01; renal tissue P <0.05). Administration of L-Arg to Fe-treated groups prevented these reductions. L-NAME increased iron-induced toxicity significantly, demonstrated by further reduction in the vitamin E levels and renal function compared to the Fe group alone. We concluded that NO plays an important role in protecting the kidney from iron-induced nephrotoxicity. NO synthase blockade enhances iron-mediated renal toxicity in this model.

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Tubulointerstitial Biomarkers for Diabetic Nephropathy

Journal of Diabetes Research ◽

10.1155/2018/2852398 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 15

Author(s):

Bancha Satirapoj

Keyword(s):

Diabetic Nephropathy ◽

Tissue Injury ◽

Kidney Injury ◽

Cardiovascular Complications ◽

Renal Tissue ◽

Monocyte Chemoattractant Protein 1 ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Potential Applications ◽

Novel Biomarkers ◽

Kidney Injury Molecule 1

Patients with diabetic nephropathy have a higher risk of mortality, mostly from cardiovascular complications. Standard biomarkers including serum creatinine, estimated glomerular filtration rate, and albuminuria are imprecise, do not directly measure renal tissue injury, and are relatively insensitive to small changes in renal function. Thus, availability of novel biomarkers that are sensitive, specific, and precise as well as able to detect kidney injury and predict clinically significant outcomes would be widely useful in diabetic nephropathy. Novel biomarkers of the processes that induce tubulointerstitial changes may ultimately prove to better predict renal progression and prognosis in type 2 diabetes. Recently, certain biomarkers, which were initially identified in acute kidney injury, also have been reported to confer value in evaluating patients with chronic kidney disease. Biomarkers such as cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), angiotensinogen, periostin, and monocyte chemoattractant protein-1 (MCP-1) reflect tubular injury. In this article, we focused on the potential applications of these biomarkers in diabetic nephropathy.

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