Hypoxia inducible factor-1α accumulation in steatotic liver preservation: Role of nitric oxide

Zaoualí, Mohamed Amine; Mosbah, Ismaïl Ben; Boncompagni, Eleonora; Abdennebi, Hassen Ben; Mitjavila, M. T.; Bartrons, Ramón; Freitas, Isabel; Rimola, Antoni; Roselló‐Catafau, Joan

doi:10.3748/wjg.v16.i28.3499

Cited by 51 publications

(70 citation statements)

References 50 publications

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“…Moreover, HIF-1a upregulation was associated with better preservation of steatotic and nonsteatotic liver grafts (Zaouali et al, 2010a). Our results show that HIF-1a and its target Epo mRNA expression were downregulated after cold ischemia reperfusion.…”

Section: Acetazolamide Protects Fatty Liver Against Ischemic Damagesupporting

confidence: 52%

“…HIF-1a is a key transcriptional factor mediating cellular adaptation under stress conditions, including IRI. Indeed, it plays an important role in fatty liver protection against cold IRI, and its protective action is related to its downstream proteins, including Epo and eNOS (Zaouali et al, 2010a;Eipel et al, 2012). Moreover, HIF-1a has been implicated in the AZ beneficial effects against renal IRI and in the case of acute mountain sickness ).…”

Section: Discussionmentioning

confidence: 99%

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Acetazolamide Protects Steatotic Liver Grafts against Cold Ischemia Reperfusion Injury

Béjaoui

Pantazi

Luca

et al. 2015

J Pharmacol Exp Ther

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Ischemia reperfusion injury (IRI) is a primary concern in liver transplantation, especially when steatosis is present. Acetazolamide (AZ), a specific carbonic anhydrase (CA) inhibitor, has been suggested to protect against hypoxia. Here, we hypothesized that AZ administration could be efficient to protect fatty livers against cold IRI. Obese Zucker rat livers were preserved in Institut Georges Lopez-1 storage solution for 24 hours at 4°C and ex vivo perfused for 2 hours at 37°C. Alternatively, rats were also treated with intravenous injection of AZ (30 mg/kg) before liver recovery. Liver injury, hepatic function, and vascular resistance were determined. CA II protein levels and CA hydratase activity were assessed as well as other parameters involved in IRI (endothelial nitric oxide synthase, mitogen activated protein kinase family, hypoxic inducible factor 1 alpha, and erythropoietin). We demonstrated that AZ administration efficiently protects the steatotic liver against cold IRI. AZ protection was associated with better function, decreased vascular resistance, and activation of endothelial nitric oxide synthase. This was consistent with an effective mitogen activated protein kinase inactivation. Finally, no effect on the hypoxic inductible factor 1 alpha/erythropoietin pathway was observed. The present study demonstrated that AZ administration is a suitable pharmacological strategy for preserving fatty liver grafts against cold IRI.

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Section: Acetazolamide Protects Fatty Liver Against Ischemic Damagesupporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Acetazolamide Protects Steatotic Liver Grafts against Cold Ischemia Reperfusion Injury

Béjaoui

Pantazi

Luca

et al. 2015

J Pharmacol Exp Ther

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“…Five studies reported similar increases in nitrates/nitrites in both steatotic and lean livers post-IRI [69,[74][75][76][77] while the remaining 5 studies reported a greater increase in levels of nitrates/nitrites in steatotic livers post-IRI [46,57,65,66,72]. While the role of NO in the susceptibility of steatotic livers is still controversial, when a NO-inhibitor (L-NAME) was added to the preservation solution or given to the donor animal prior to surgery, hepatic function decreased more in steatotic livers post-IRI than in lean livers [57,74,76,77].…”

Section: Role Of Nitric Oxide In Steatotic Liversmentioning

confidence: 87%

“…Eight of the 63 studies reported HO-1 levels in steatotic livers. Four studies reported a greater increase in HO-1 levels in steatotic livers post-warm IRI [20,21,31,35] whereas in cold PRI, 2 studies showed similar increase in HO-1 levels in both types of liver [69,74] and another two studies showed decreased HO-1 protein levels in steatotic livers [60,76].…”

Section: Insulin-like Growth Factormentioning

confidence: 99%

“…The reactive iron released follows detoxification pathways and also stimulates the synthesis of ferritin, promoting a secondary cellular desensitization to oxidative stress [119]. Only one study reported HIF-1α levels with no difference between the groups of liver post-IRI [74]. Eight of the 63 studies reported HO-1 levels in steatotic livers.…”

Section: Insulin-like Growth Factormentioning

confidence: 99%

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Effect of Hepatic Steatosis on Bioenergetic Function During Hepatic Ischemia-reperfusion: A Systematic Review

Chu¹

2013

TOTRANSJ

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Abstract:Background: The impact of hepatic steatosis on bioenergetics following hepatic ischemia-reperfusion injury (IRI) remains controversial and is associated with variable reports on its outcome. Large numbers of studies have been published examining the relationship between hepatic steatosis and cellular bioenergetics following hepatic IRI. This systematic review evaluates these studies.Methods: An electronic search of the Medline and Embase databases (January 1946 to June 2012) was performed to select studies that reported relevant outcomes in animal models or patients with hepatic steatosis subjected to IRI.Results: A total of 489 articles were identified, of which 63 animal studies met the predefined criteria and were included in the study. There was large variation in the type of animal model, duration and type of IRI utilized and histological description of hepatic steatosis. Bioenergetic impairments appear to increase the susceptibility of steatotic livers to IRI. The most common impairment was decreased adenosine triphosphate recovery with increased oxidative stress following IRI. Impaired mitochondrial function play a key role in the susceptibility of steatotic livers to IRI.Conclusions: Animals with >30% hepatic steatosis have been shown to have poor outcome following IRI. Despite limitations of different experimental models and inconsistency in histological description, impaired mitochondrial function and bioenergetics appear to be important mediators in the decreased tolerance of steatotic livers to IRI. Future studies need to be consistent and clinically relevant to further improve our understanding of this issue.

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HIF‐1α Expression as a Protective Strategy of HepG2 Cells Against Fatty Acid‐Induced Toxicity

Yoo

Noh

Ahn

et al. 2014

J of Cellular Biochemistry

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Free fatty acid-induced lipotoxicity via increased endoplasmic reticulum (ER) stress and hepatocyte apoptosis is a key pathological mechanism of non-alcoholic steatohepatitis. A role of hypoxia-inducible factor 1α (HIF-1α) in this process has been suggested, but direct evidence is lacking. Here, we used HepG2 cells as a model to study whether HIF-1α can reduce palmitic acid-induced lipotoxicity and ER stress. In HepG2 cells treated with 500 µM palmitic acid, HIF-1α expression increased transiently, the decline was associated with increased cleaved caspase-3 expression. Overexpression and knockdown of HIF-1α decreased and exacerbated, respectively, palmitic acid-induced lipoapoptosis. The overexpression also blunted upregulation of the ER stress markers, C/EBP homologous protein (CHOP) and chaperone immunoglobulin heavy chain binding protein (Bip), while the knockdown increased the level of CHOP. In line with this, CHOP promoter activity decreased following HIF-1α binding to the CHOP promoter hypoxia response element. These results indicate that hepatocyte lipotoxicity is associated with decreased HIF-1α expression. It also suggests that upregulation of HIF-1α can be a possible strategy to reduce lipotoxicity in non-alcoholic fatty liver disease.

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Hypoxia inducible factor-1α accumulation in steatotic liver preservation: Role of nitric oxide

Abstract: We found evidence for the role of the HIF-1alpha/NO system in fatty liver preservation, especially when IGL-1 solution is used.

Cited by 51 publications

References 50 publications

Acetazolamide Protects Steatotic Liver Grafts against Cold Ischemia Reperfusion Injury

Acetazolamide Protects Steatotic Liver Grafts against Cold Ischemia Reperfusion Injury

Effect of Hepatic Steatosis on Bioenergetic Function During Hepatic Ischemia-reperfusion: A Systematic Review

HIF‐1α Expression as a Protective Strategy of HepG2 Cells Against Fatty Acid‐Induced Toxicity

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