scholarly journals Heme Oxygenase-1 in Gastrointestinal Tract Health and Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1214
Author(s):  
Jose D. Puentes-Pardo ◽  
Sara Moreno-SanJuan ◽  
Ángel Carazo ◽  
Josefa León
Keyword(s):  
Gastrointestinal Tract ◽  
Heme Oxygenase ◽  
Oxidative Degradation ◽  
Heme Oxygenase 1 ◽  
Beneficial Effects ◽  
Downstream Effectors ◽  
Inflammatory Processes ◽  
Health And Disease ◽  
Cytoprotective Agent ◽  
Inflammatory Bowel

Heme oxygenase 1 (HO-1) is the rate-limiting enzyme of heme oxidative degradation, generating carbon monoxide (CO), free iron, and biliverdin. HO-1, a stress inducible enzyme, is considered as an anti-oxidative and cytoprotective agent. As many studies suggest, HO-1 is highly expressed in the gastrointestinal tract where it is involved in the response to inflammatory processes, which may lead to several diseases such as pancreatitis, diabetes, fatty liver disease, inflammatory bowel disease, and cancer. In this review, we highlight the pivotal role of HO-1 and its downstream effectors in the development of disorders and their beneficial effects on the maintenance of the gastrointestinal tract health. We also examine clinical trials involving the therapeutic targets derived from HO-1 system for the most common diseases of the digestive system.

Products of heme oxygenase and their potential therapeutic applications

2006 ◽  
Vol 290 (3) ◽  
pp. F563-F571 ◽  
Author(s):  
Kristin A. Kirkby ◽  
Christopher A. Adin
Keyword(s):  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Inexpensive Method ◽  
Waste Products ◽  
Biliverdin Reductase ◽  
Therapeutic Applications ◽  
Beneficial Effects ◽  
Tissue Protection ◽  
Organ Systems ◽  
Dose Dependent

Heme oxygenase 1 (HO-1) is induced in response to cellular stress and is responsible for converting the prooxidant heme molecule into equimolar quantities of biliverdin (BV), carbon monoxide (CO), and iron. BV is then converted to bilirubin (BR) by the enzyme biliverdin reductase. Experimental evidence suggests that induction of the HO system is an important endogenous mechanism for cytoprotection and that the downstream products of heme degradation, CO, BR, and BV, may mediate these powerful beneficial effects. These molecules, which were once considered to be toxic metabolic waste products, have recently been shown to have dose-dependent vasodilatory, antioxidant, and anti-inflammatory properties that are particularly desirable for tissue protection during organ transplantation. In fact, recent work has demonstrated that administration of exogenous CO, BR, or BV may offer a simple, inexpensive method to substitute for the cytoprotective effects of HO-1 in a variety of clinically applicable models. This review will attempt to summarize the relevant biochemical and cytoprotective properties of CO, BR, and BV, and will discuss emerging studies involving the therapeutic applications of these molecules in the kidney and other organ systems.

Use of Synbiotics for Ulcerative Colitis Treatment

2020 ◽  
Vol 15 (3) ◽  
pp. 174-182 ◽  
Author(s):  
Marianna Roselli ◽  
Alberto Finamore
Keyword(s):  
Ulcerative Colitis ◽  
Gastrointestinal Tract ◽  
Intestinal Microbiota ◽  
Strong Impact ◽  
Beneficial Effects ◽  
System A ◽  
Bowel Diseases ◽  
Ulcerative Colitis Treatment ◽  
Inflammatory Bowel

Inflammatory bowel diseases, namely Crohn's disease and ulcerative colitis, are currently considered multifactorial pathologies in which various combined environmental factors act on genetic background, giving rise to chronic inflammation of the gastrointestinal tract. Ulcerative colitis is an inflammation of the colon caused by a dysregulated immune response to host intestinal microbiota in genetically susceptible subjects. Ulcerative colitis has a strong impact on patients' quality of life, as well as high costs for the health-care system. A great interest on the role of intestinal microbiota modulation in ulcerative colitis is emerging. Several studies have shown an improvement of inflammatory markers and symptoms in ulcerative colitis patients through treatments with probiotics and prebiotics separately. Despite the low number of studies on the treatment of ulcerative colitis by specific strains of probiotics plus selected prebiotics, i.e. synbiotics, the results are promising, even if discordant. The mechanism of action in synbiotics supplementation is still unclear and needs more investigation, although there is a large number of data indicating that the synergism between probiotics and prebiotics favours the survival and implantation of probiotics into the gastrointestinal tract with beneficial effects on human health by modulating the inflammatory response and gut microbiota composition. The aim of this minireview is to describe the main in vitro, animal and human studies performed up to now, that have used synbiotics to treat ulcerative colitis, and to highlight limitations and future perspectives.

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 Omega Fatty Acids and Inflammatory Bowel Diseases: An Overview

2019 ◽  
Vol 20 (19) ◽  
pp. 4851 ◽  
Author(s):  
Ledyane Taynara Marton ◽  
Ricardo de Alvares Goulart ◽  
Antonelly Cassio Alves de Carvalho ◽  
Sandra Maria Barbalho
Keyword(s):  
Fatty Acids ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Omega 3 ◽  
Beneficial Effects ◽  
Ω3 Fatty Acids ◽  
Number Of Patients ◽  
Bowel Diseases ◽  
Inflammatory Processes ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBD) are chronic, inflammatory processes that affect the gastrointestinal tract and are mainly represented by ulcerative colitis (UC) and Crohn’s disease (CD). Omega 3 (ω3) fatty acids (eicosapentanoic acid and docosahexaenoic acid) show an indispensable role in the inflammatory processes and, for these reasons, we aimed to review the effects of these acids on UC and CD. Databases such as PUMED and EMBASE were searched, and the final selection included fifteen studies that fulfilled the inclusion criteria. The results showed that ω3 fatty acids reduce intestinal inflammation, induce and maintain clinical remission in UC patients, and are related with the reduction of proinflammatory cytokines, decrease disease activity and increase the quality of life of CD patients. Furthermore, the consumption of these fatty acids may be related to a reduced risk of developing IBD. Many studies have shown the beneficial effects of ω3 as adjunctive in the treatment or prevention of UC or CD. Nevertheless, most were performed with a small number of patients and there are many variations in the mode of consumption, the type of food or the type of formulation used. All these factors substantially interfere with the results and do not allow reliable comparisons.

Heme Oxygenase-1 in Kidney Health and Disease

2019 ◽  
pp. 205-216
Author(s):  
Pu Duann ◽  
Elias A. Lianos ◽  
Pei-Hui Lin
Keyword(s):  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Health And Disease ◽  
Kidney Health

scholarly journals Heme Oxygenase-1 Induction and Organic Nitrate Therapy: Beneficial Effects on Endothelial Dysfunction, Nitrate Tolerance, and Vascular Oxidative Stress

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Andreas Daiber ◽  
Matthias Oelze ◽  
Philip Wenzel ◽  
Franziska Bollmann ◽  
Andrea Pautz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Side Effects ◽  
Endothelial Dysfunction ◽  
Heme Oxygenase ◽  
Nitrate Tolerance ◽  
Heme Oxygenase 1 ◽  
Organic Nitrate ◽  
Organic Nitrates ◽  
Beneficial Effects ◽  
Vascular Oxidative Stress

Organic nitrates are a group of very effective anti-ischemic drugs. They are used for the treatment of patients with stable angina, acute myocardial infarction, and chronic congestive heart failure. A major therapeutic limitation inherent to organic nitrates is the development of tolerance, which occurs during chronic treatment with these agents, and this phenomenon is largely based on induction of oxidative stress with subsequent endothelial dysfunction. We therefore speculated that induction of heme oxygenase-1 (HO-1) could be an efficient strategy to overcome nitrate tolerance and the associated side effects. Indeed, we found that hemin cotreatment prevented the development of nitrate tolerance and vascular oxidative stress in response to chronic nitroglycerin therapy. Vice versa, pentaerithrityl tetranitrate (PETN), a nitrate that was previously reported to be devoid of adverse side effects, displayed tolerance and oxidative stress when the HO-1 pathway was blocked pharmacologically or genetically by using HO-1+/–mice. Recently, we identified activation of Nrf2 and HuR as a principle mechanism of HO-1 induction by PETN. With the present paper, we present and discuss our recent and previous findings on the role of HO-1 for the prevention of nitroglycerin-induced nitrate tolerance and for the beneficial effects of PETN therapy.

Heme oxygenase-1 induction improves ischemic renal failure: role of nitric oxide and peroxynitrite

2007 ◽  
Vol 293 (6) ◽  
pp. H3542-H3549 ◽  
Author(s):  
Miguel G. Salom ◽  
Susana Nieto Cerón ◽  
Francisca Rodriguez ◽  
Bernardo Lopez ◽  
Isabel Hernández ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Acute Renal Failure ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Beneficial Effects ◽  
Medullary Blood Flow ◽  
Ischemic Renal Failure ◽  
Oxide Synthase

The present study evaluated the effects of heme oxygenase-1 (HO-1) induction on the changes in renal outer medullary nitric oxide (NO) and peroxynitrite levels during 45-min renal ischemia and 30-min reperfusion in anesthetized rats. Glomerular filtration rate (GFR), outer medullary blood flow (OMBF), HO and nitric oxide synthase (NOS) isoform expression, and renal low-molecular-weight thiols (–SH) were also determined. During ischemia significant increases in NO levels and peroxynitrite signal were observed (from 832.1 ± 129.3 to 2,928.6 ± 502.0 nM and from 3.8 ± 0.7 to 9.0 ± 1.6 nA before and during ischemia, respectively) that dropped to preischemic levels during reperfusion. OMBF and –SH significantly decreased after 30 min of reperfusion. Twenty-four hours later, an acute renal failure was observed (GFR 923.0 ± 66.0 and 253.6 ± 55.3 μl·min−1·g kidney wt−1 in sham-operated and ischemic kidneys, respectively; P < 0.05). The induction of HO-1 (CoCl2 60 mg/kg sc, 24 h before ischemia) decreased basal NO concentration (99.7 ± 41.0 nM), although endothelial and neuronal NOS expression were slightly increased. CoCl2 administration also blunted the ischemic increase in NO and peroxynitrite (maximum values of 1,315.6 ± 445.6 nM and 6.3 ± 0.5 nA, respectively; P < 0.05), preserving postischemic OMBF and GFR (686.4 ± 45.2 μl·min−1·g kidney wt−1). These beneficial effects of CoCl2 on ischemic acute renal failure seem to be due to HO-1 induction, because they were abolished by stannous mesoporphyrin, a HO inhibitor. In conclusion, HO-1 induction has a protective effect on ischemic renal failure that seems to be partially mediated by decreasing the excessive production of NO with the subsequent reduction in peroxynitrite formation observed during ischemia.

scholarly journals Therapeutic Potential of Heme Oxygenase-1/Carbon Monoxide in Lung Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-19 ◽  
Author(s):  
Myrna Constantin ◽  
Alexander J. S. Choi ◽  
Suzanne M. Cloonan ◽  
Stefan W. Ryter
Keyword(s):  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Heme Oxygenase 1 ◽  
Protective Mechanism ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Oxidative Breakdown ◽  
Biliverdin Ix

Heme oxygenase (HO), a catabolic enzyme, provides the rate-limiting step in the oxidative breakdown of heme, to generate carbon monoxide (CO), iron, and biliverdin-IXα. Induction of the inducible form, HO-1, in tissues is generally regarded as a protective mechanism. Over the last decade, considerable progress has been made in defining the therapeutic potential of HO-1 in a number of preclinical models of lung tissue injury and disease. Likewise, tissue-protective effects of CO, when applied at low concentration, have been observed in many of these models. Recent studies have expanded this concept to include chemical CO-releasing molecules (CORMs). Collectively, salutary effects of the HO-1/CO system have been demonstrated in lung inflammation/acute lung injury, lung and vascular transplantation, sepsis, and pulmonary hypertension models. The beneficial effects of HO-1/CO are conveyed in part through the inhibition or modulation of inflammatory, apoptotic, and proliferative processes. Recent advances, however, suggest that the regulation of autophagy and the preservation of mitochondrial homeostasis may serve as additional candidate mechanisms. Further preclinical and clinical trials are needed to ascertain the therapeutic potential of HO-1/CO in human clinical disease.

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