HO-1 mitigates acute kidney injury and subsequent kidney-lung cross-talk

Rossi, Maxime; Delbauve, Sandrine; Roumeguère, Thierry; Wespes, Eric; Léo, Oberdan; Flamand, Véronique; Moine, Alaín Le; Hougardy, Jean-Michel

doi:10.1080/10715762.2019.1668936

Cited by 27 publications

(17 citation statements)

References 35 publications

(57 reference statements)

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“…Preemptive induction of HO-1 by using hemin is largely known to be an efficient protective strategy against renal IRI in animal models [20] , [21] . Renal IRI also promotes systemic release of pro-inflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α) that induces a systemic inflammatory response, resulting in proinflammatory cells recruitment and remote organ damage, particularly in lung [22] .…”

Section: Evidence Supporting Ho-1 As a Potential Targetmentioning

confidence: 99%

“…Basically, hemin-induced HO-1 improves renal outcomes after renal IRI by decreasing level of various renal proinflammatory cytokines, including IL-1β, IL-6, TNF-α, KC (keratinocyte chemoattractant also called CXCL1, a chemokine involved in neutrophils influx), and MCP-1 [20] , [22] . Moreover, it has been shown that hemin-induced HO-1 reduces IRI-induced cytokine storm and subsequent lung injury by decreasing plasma level of IL-6 and KC, and lung inflammation (neutrophils influx and lung KC) [22] .…”

Section: Evidence Supporting Ho-1 As a Potential Targetmentioning

confidence: 99%

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Heme oxygenase-1 (HO-1) cytoprotective pathway: A potential treatment strategy against coronavirus disease 2019 (COVID-19)-induced cytokine storm syndrome

et al. 2020

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The outbreak of coronavirus disease 2019 (COVID-19) requires urgent need for effective treatment. Severe COVID-19 is characterized by a cytokine storm syndrome with subsequent multiple organ failure (MOF) and acute respiratory distress syndrome (ARDS), which may lead to intensive care unit and increased risk of death. While awaiting a vaccine, targeting COVID-19-induced cytokine storm syndrome appears currently as the efficient strategy to reduce the mortality of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The stress-responsive enzyme, heme oxygenase-1 (HO-1) is largely known to protect against inflammatory response in animal models. HO-1 is induced by hemin, a well-tolerated molecule, used for decades in the treatment of acute intermittent porphyria. Experimental studies showed that hemin-induced HO-1 mitigates cytokine storm and lung injury in mouse models of sepsis and renal ischemia-reperfusion injury. Furthermore, HO-1 may also control numerous viral infections by inhibiting virus replication. In this context, we suggest the hypothesis that HO-1 cytoprotective pathway might be a promising target to control SARS-CoV-2 infection and mitigate COVID-19-induced cytokine storm and subsequent ARDS.

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Section: Evidence Supporting Ho-1 As a Potential Targetmentioning

confidence: 99%

Section: Evidence Supporting Ho-1 As a Potential Targetmentioning

confidence: 99%

Heme oxygenase-1 (HO-1) cytoprotective pathway: A potential treatment strategy against coronavirus disease 2019 (COVID-19)-induced cytokine storm syndrome

et al. 2020

Self Cite

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“…Deficiency of HO-1 is thus associated with persistent hemolytic anemia, iron accumulation in tissues, chronic inflammation, and microcirculation disturbances in both humans [55,56] and mice [57]. Conversely, overexpression of HO-1 contributes to the resolution of inflammation and vascular dysfunction, suggesting the upregulation of HO-1 as a therapeutic strategy for various diseases, especially cardiovascular [58,59] and renal diseases [60]: this strategy remains controversial, however [61].…”

Section: Heme—its Structure Metabolism and Detoxificationmentioning

confidence: 99%

Hemolysis Derived Products Toxicity and Endothelium: Model of the Second Hit

Frimat

Boudhabhay

Roumenina

2019

Toxins

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Vascular diseases are multifactorial, often requiring multiple challenges, or ‘hits’, for their initiation. Intra-vascular hemolysis illustrates well the multiple-hit theory where a first event lyses red blood cells, releasing hemolysis-derived products, in particular cell-free heme which is highly toxic for the endothelium. Physiologically, hemolysis derived-products are rapidly neutralized by numerous defense systems, including haptoglobin and hemopexin which scavenge hemoglobin and heme, respectively. Likewise, cellular defense mechanisms are involved, including heme-oxygenase 1 upregulation which metabolizes heme. However, in cases of intra-vascular hemolysis, those systems are overwhelmed. Heme exerts toxic effects by acting as a damage-associated molecular pattern and promoting, together with hemoglobin, nitric oxide scavenging and ROS production. In addition, it activates the complement and the coagulation systems. Together, these processes lead to endothelial cell injury which triggers pro-thrombotic and pro-inflammatory phenotypes. Moreover, among endothelial cells, glomerular ones display a particular susceptibility explained by a weaker capacity to counteract hemolysis injury. In this review, we illustrate the ‘multiple-hit’ theory through the example of intra-vascular hemolysis, with a particular focus on cell-free heme, and we advance hypotheses explaining the glomerular susceptibility observed in hemolytic diseases. Finally, we describe therapeutic options for reducing endothelial injury in hemolytic diseases.

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“…Thus, it seems that SAD mouse kidney responded appropriately to H/R stimuli as compared to control mice. Based on a recent study (Rossi et al., ) which reported that hemin‐induced HO‐1 prevents acute kidney injury, we may hypothesize that the higher levels of total plasma haem in SAD vs . C57 mice (Merle et al., ) at basal state could explain the more appropriate response to stress in SAD mice.…”

Section: Discussionmentioning

confidence: 99%

Effects of hypoxia–reoxygenation stimuli on renal redox status and nuclear factor erythroid 2‐related factor 2 pathway in sickle cell SAD mice

Faes

Juban

Aufradet

et al. 2020

Experimental Physiology

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Hypoxia-reoxygenation (H/R) stress is known to increase oxidative stress in transgenic sickle mice and can cause organ failure. Here we described the effects of H/R on nuclear factor erythroid 2-related factor 2 (Nrf2) as a putative regulator of redox status in the kidneys of SAD mice investigating Nrf2-regulated antioxidant enzymes. Transgenic SAD mice and healthy C57Bl/6J mice were exposed to 4 h of hypoxia followed by various times of reoxygenation at ambient air (2 or 6 h). Regardless of the conditions (i.e. normoxia or H/R), SAD mice expressed higher renal oxidative stress levels. Nuclear Nrf2 protein expression decreased after 2 h post-hypoxia only in the medulla region of the kidney and only in SAD mice. Simultaneously, haem oxygenase transcripts were affected by H/R stimulus with a significant enhancement after 2 h post-hypoxia.Similarly, hypoxia inducible factor-1 staining increased after 2 h post-hypoxia in SAD mice in both cortex and medulla areas. Our data confirm that the kidneys are organs that are particularly sensitive to H/R stimuli in sickle cell SAD mice. Also, these results suggest an effect of the duration of recovery period (short vs. long) and specific responses according to kidney areas, medulla vs.cortex, on Nrf2 expression in response to H/R stimuli in SAD mice. K E Y W O R D Santioxidant response, hypoxia-inducible factor-1 , renal injury

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HO-1 mitigates acute kidney injury and subsequent kidney-lung cross-talk

Cited by 27 publications

References 35 publications

Heme oxygenase-1 (HO-1) cytoprotective pathway: A potential treatment strategy against coronavirus disease 2019 (COVID-19)-induced cytokine storm syndrome

Heme oxygenase-1 (HO-1) cytoprotective pathway: A potential treatment strategy against coronavirus disease 2019 (COVID-19)-induced cytokine storm syndrome

Hemolysis Derived Products Toxicity and Endothelium: Model of the Second Hit

Effects of hypoxia–reoxygenation stimuli on renal redox status and nuclear factor erythroid 2‐related factor 2 pathway in sickle cell SAD mice

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