scholarly journals Heme Oxygenase in Kidney Disease

2004 ◽  
Vol 2 (1) ◽  
pp. 37
Author(s):  
Se Ho Jang
Keyword(s):  
Kidney Disease ◽  
Heme Oxygenase

scholarly journals Heme Oxygenase 1: A Defensive Mediator in Kidney Diseases

2021 ◽  
Vol 22 (4) ◽  
pp. 2009
Author(s):  
Anne Grunenwald ◽  
Lubka T. Roumenina ◽  
Marie Frimat
Keyword(s):  
Kidney Disease ◽  
Heme Oxygenase ◽  
Current Knowledge ◽  
Kidney Diseases ◽  
Heme Oxygenase 1 ◽  
Wide Range ◽  
Significant Burden ◽  
Stage Renal Disease ◽  
End Stage ◽  
Positive Effect

The incidence of kidney disease is rising, constituting a significant burden on the healthcare system and making identification of new therapeutic targets increasingly urgent. The heme oxygenase (HO) system performs an important function in the regulation of oxidative stress and inflammation and, via these mechanisms, is thought to play a role in the prevention of non-specific injuries following acute renal failure or resulting from chronic kidney disease. The expression of HO-1 is strongly inducible by a wide range of stimuli in the kidney, consequent to the kidney’s filtration role which means HO-1 is exposed to a wide range of endogenous and exogenous molecules, and it has been shown to be protective in a variety of nephropathological animal models. Interestingly, the positive effect of HO-1 occurs in both hemolysis- and rhabdomyolysis-dominated diseases, where the kidney is extensively exposed to heme (a major HO-1 inducer), as well as in non-heme-dependent diseases such as hypertension, diabetic nephropathy or progression to end-stage renal disease. This highlights the complexity of HO-1’s functions, which is also illustrated by the fact that, despite the abundance of preclinical data, no drug targeting HO-1 has so far been translated into clinical use. The objective of this review is to assess current knowledge relating HO-1’s role in the kidney and its potential interest as a nephroprotection agent. The potential therapeutic openings will be presented, in particular through the identification of clinical trials targeting this enzyme or its products.

scholarly journals Heme Oxygenase-1 as a Target for TGF-β in Kidney Disease

2012 ◽  
Vol 32 (3) ◽  
pp. 277-286 ◽  
Author(s):  
Abolfazl Zarjou ◽  
Anupam Agarwal
Keyword(s):  
Kidney Disease ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1

scholarly journals A new model of an arteriovenous fistula in chronic kidney disease in the mouse: beneficial effects of upregulated heme oxygenase-1

2016 ◽  
Vol 310 (6) ◽  
pp. F466-F476 ◽  
Author(s):  
Lu Kang ◽  
Joseph P. Grande ◽  
Matthew L. Hillestad ◽  
Anthony J. Croatt ◽  
Michael A. Barry ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Blood Flow ◽  
Kidney Disease ◽  
Arteriovenous Fistula ◽  
Heme Oxygenase ◽  
Viral Gene ◽  
Heme Oxygenase 1 ◽  
Beneficial Effects ◽  
Viral Gene Delivery ◽  
Venous Wall

The arteriovenous fistula (AVF) is the preferred hemodialysis vascular access, but it is complicated by high failure rates and attendant morbidity. This study provides the first description of a murine AVF model that recapitulates two salient features of hemodialysis AVFs, namely, anastomosis of end-vein to side-artery to create the AVF and the presence of chronic kidney disease (CKD). CKD reduced AVF blood flow, observed as early as 3 days after AVF creation, and increased neointimal hyperplasia, venous wall thickness, thrombus formation, and vasculopathic gene expression in the AVF. These adverse effects of CKD could not be ascribed to preexisting alterations in blood pressure or vascular reactivity in this CKD model. In addition to vasculopathic genes, CKD induced potentially vasoprotective genes in the AVF such as heme oxygenase-1 (HO-1) and HO-2. To determine whether prior HO-1 upregulation may protect in this model, we upregulated HO-1 by adeno-associated viral gene delivery, achieving marked venous induction of the HO-1 protein and HO activity. Such HO-1 upregulation improved AVF blood flow and decreased venous wall thickness in the AVF. Finally, we demonstrate that the administration of carbon monoxide, a product of HO, acutely increased AVF blood flow. This study thus demonstrates: 1) the feasibility of a clinically relevant murine AVF model created in the presence of CKD and involving an end-vein to side-artery anastomosis; 2) the exacerbatory effect of CKD on clinically relevant features of this model; and 3) the beneficial effects in this model conferred by HO-1 upregulation by adeno-associated viral gene delivery.

scholarly journals Immunomodulatory Effects of Heme Oxygenase-1 in Kidney Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Yunlong Li ◽  
Kuai Ma ◽  
Zhongyu Han ◽  
Mingxuan Chi ◽  
Xiyalatu Sai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Heme Oxygenase ◽  
Cell Cycle Progression ◽  
Immune Cell ◽  
Kidney Diseases ◽  
General Term ◽  
New Drugs ◽  
Heme Oxygenase 1 ◽  
Multiple Processes

Kidney disease is a general term for heterogeneous damage that affects the function and the structure of the kidneys. The rising incidence of kidney diseases represents a considerable burden on the healthcare system, so the development of new drugs and the identification of novel therapeutic targets are urgently needed. The pathophysiology of kidney diseases is complex and involves multiple processes, including inflammation, autophagy, cell-cycle progression, and oxidative stress. Heme oxygenase-1 (HO-1), an enzyme involved in the process of heme degradation, has attracted widespread attention in recent years due to its cytoprotective properties. As an enzyme with known anti-oxidative functions, HO-1 plays an indispensable role in the regulation of oxidative stress and is involved in the pathogenesis of several kidney diseases. Moreover, current studies have revealed that HO-1 can affect cell proliferation, cell maturation, and other metabolic processes, thereby altering the function of immune cells. Many strategies, such as the administration of HO-1-overexpressing macrophages, use of phytochemicals, and carbon monoxide-based therapies, have been developed to target HO-1 in a variety of nephropathological animal models, indicating that HO-1 is a promising protein for the treatment of kidney diseases. Here, we briefly review the effects of HO-1 induction on specific immune cell populations with the aim of exploring the potential therapeutic roles of HO-1 and designing HO-1-based therapeutic strategies for the treatment of kidney diseases.

scholarly journals Renal protection in chronic kidney disease: hypoxia-inducible factor activation vs. angiotensin II blockade

2010 ◽  
Vol 299 (6) ◽  
pp. F1365-F1373 ◽  
Author(s):  
Aihua Deng ◽  
Mary Ann K. Arndt ◽  
Joseph Satriano ◽  
Prabhleen Singh ◽  
Timo Rieg ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Oxygen Consumption ◽  
Angiotensin Ii ◽  
Kidney Disease ◽  
Real Time ◽  
Heme Oxygenase ◽  
Real Time Pcr ◽  
Hypoxia Inducible Factor ◽  
Heme Oxygenase 1 ◽  
Ang Ii

The 5/6thnephrectomy or ablation/infarction (A/I) preparation has been used as a classic model of chronic kidney disease (CKD). We observed increased kidney oxygen consumption (QO2) and altered renal hemodynamics in the A/I kidney that were normalized after combined angiotensin II (ANG II) blockade. Studies suggest hypoxia inducible factor as a protective influence in A/I. We induced hypoxia-inducible factor (HIF) and HIF target proteins by two different methods, cobalt chloride (CoCl2) and dimethyloxalyglycine (DMOG), for the first week after creation of A/I and compared the metabolic and renal hemodynamic outcomes to combined ANG II blockade. We also examined the HIF target proteins expressed by using Western blots and real-time PCR. Treatment with DMOG, CoCl2, and ANG II blockade normalized kidney oxygen consumption factored by Na reabsorption and increased both renal blood flow and glomerular filtration rate. At 1 wk, CoCl2and DMOG increased kidney expression of HIF by Western blot. In the untreated A/I kidney, VEGF, heme oxygenase-1, and GLUT1 were all modestly increased. Both ANG II blockade and CoCl2therapy increased VEGF and GLUT1 but the cobalt markedly so. ANG II blockade decreased heme oxygenase-1 expression while CoCl2increased it. By real-time PCR, erythropoietin and GLUT1 were only increased by CoCl2therapy. Cell proliferation was modestly increased by ANG II blockade but markedly after cobalt therapy. Metabolic and hemodynamic abnormalities were corrected equally by ANG II blockade and HIF therapies. However, the molecular patterns differed significantly between ANG II blockade and cobalt therapy. HIF induction may prove to be protective in this model of CKD.

scholarly journals P0916OLIVE LEAF EXTRACT IMPROVES RENAL ANTIOXIDANT DEFENSE WITHOUT ALTERING THE HEME OXYGENASE-1/BILIVERDIN REDUCTASE PATHWAY IN HYPERTENSIVE RATS WITH FOCAL SEGMENTAL GLOMERULOSCLEROSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Danijela Karanovic ◽  
Nevena Mihailovic-Stanojevic ◽  
Zoran Miloradovic ◽  
Milan Ivanov ◽  
Jelica Grujic-Milanovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Western Blot ◽  
Heme Oxygenase ◽  
Leaf Extract ◽  
Model Group ◽  
Hypertensive Rats ◽  
Biliverdin Reductase ◽  
Protein Expressions

Abstract Background and Aims Oxidative stress is implicated in the pathophysiology of chronic kidney disease. Previously, we showed that adriamycin (anticancer agent, enhances reactive oxygen species production) induced focal segmental glomerular sclerosis (FSGS) with massive proteinuria in spontaneously hypertensive rats (SHR). The heme oxygenase (HO) system plays an important role in regulating oxidative stress and is protective in chronic kidney disease. HO-1 is a cytoprotective enzyme that catalyzes the conversion of highly reactive free heme molecules into biliverdin, carbon monoxide, and iron. Biliverdin is subsequently converted to bilirubin by biliverdin reductase and has potent antioxidant effect. Olive leaf extract (OLE, Olea europaea L.) is rich in phenolic compounds that are known to possess powerful antioxidant properties. Here, we aimed to investigate the effects of OLE, focusing on its modulatory role on oxidative stress and HO-1/BVR pathway in the kidney of SHR with adriamycin-induced FSGS. Method Adult females SHR were divided into three groups. Control rats received vehicle. Two other groups, FSGS and FSGS+OLE, received adriamycin (2 mg/kg body weight i.v.) twice in 3-week-interval. After the second injection, FSGS+OLE group received OLE (80 mg/kg/day) by gavage for 6 weeks. Mean blood pressure (MAP), urine albumin-to-creatinine (Ualb/cr), renal HO-1 and biliverdin reductase protein expressions (Western Blot), protein carbonyl content (PCOs), and antioxidant capacity (ABTS) were analyzed. Results In FSGS group albuminuria was significantly increased in comparison to the level in control. Chronic consumption of OLE markedly, but not significantly decreased Ualb/cr compared to that in control. Analysis of renal PCOs revealed that significant enhancement of protein oxidation in the kidney of model group was reduced after OLE treatment to the level as in control. The ABTS level in kidney homogenates significantly decreased in FSGS group in comparison to the level in control. OLE significantly increased renal antioxidant capacity in FSGS+OLE group compared to that in model group. Western blot analysis of HO-1, and biliverdin reductase in the kidney revealed that protein expressions of both enzymes were significantly decreased in FSGS group compared to that in control. Following OLE treatment in FSGS+OLE group protein expressions of HO-1, and biliverdin reductase remained at similar level as in model group. No change in MAP values were observed between control and model groups. OLE significantly decreased MAP in FSGS+OLE group in comparison to the value of model group, and nearly significant reduction of MAP compared to the value of control. Conclusion Collectively, our results showed that OLE expressed its antioxidant property and improved oxidative status in the kidney of SHR with ADR-induced FSGS, independently of the HO-1/BVR pathway.

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