Metabolomic characterization of renal ischemia and reperfusion in a swine model

Malagrino, Pamella Araujo; Venturini, Gabriela; Yogi, Patrícia Schneider; Dariolli, Rafael; Padilha, Kallyandra; Kiers, Bianca; Gois, Tamiris Carneiro; Motta-Leal-Filho, Joaquim Maurício da; Takimura, Celso Kiyochi; Girardi, Adriana C. C.; Carnevale, Francisco César; Canevarolo, Rafael Renatino; Malheiros, Denise Maria Avancini Costa; Zeri, Ana Carolina de Mattos; Pereira, Alexandre C.

doi:10.1016/j.lfs.2016.05.025

Cited by 16 publications

(11 citation statements)

References 64 publications

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“…One consequence is micro-vascular disruption that causes acute kidney failure and affects long-term graft survival 8 – 10 . Previous studies have examined various aspects of IRI in kidney injury 6 , 11 , 12 , including the use of proteomic and metabolomic profiling to discover renal biomarker candidates of kidney ischemic injury 4 , 13 – 16 . In particular, mitochondrial dysfunction and metabolic changes including lactate, succinate, choline, taurine and fatty acids have been observed after renal ischemic insults 5 , 17 , 18 .…”

Section: Introductionmentioning

confidence: 99%

Proteo-metabolomics reveals compensation between ischemic and non-injured contralateral kidneys after reperfusion

Huang

Dullemen

Akhtar

et al. 2018

Sci Rep

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Ischaemia and reperfusion injury (IRI) is the leading cause of acute kidney injury (AKI), which contributes to high morbidity and mortality rates in a wide range of injuries as well as the development of chronic kidney disease. The cellular and molecular responses of the kidney to IRI are complex and not fully understood. Here, we used an integrated proteomic and metabolomic approach to investigate the effects of IRI on protein abundance and metabolite levels. Rat kidneys were subjected to 45 min of warm ischaemia followed by 4 h and 24 h reperfusion, with contralateral and separate healthy kidneys serving as controls. Kidney tissue proteomics after IRI revealed elevated proteins belonging to the acute phase response, coagulation and complement pathways, and fatty acid (FA) signalling. Metabolic changes were already evident after 4 h reperfusion and showed increased level of glycolysis, lipids and FAs, whilst mitochondrial function and ATP production was impaired after 24 h. This deficit was partially compensated for by the contralateral kidney. Such a metabolic balance counteracts for the developing energy deficit due to reduced mitochondrial function in the injured kidney.

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Section: Introductionmentioning

confidence: 99%

Proteo-metabolomics reveals compensation between ischemic and non-injured contralateral kidneys after reperfusion

Huang

Dullemen

Akhtar

et al. 2018

Sci Rep

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“…Similarly, accumulation of AHB in blood and urine and an increase in NADH/NAD + ratio in the cytoplasm has previously been related to hypoxic conditions such as extreme exercise (Landaas and Pettersen 1975; Malagrino et al 2016; Pechlivanis et al 2010, 2014). In our study, plasma NADH was below limit of detection (LOD), while NAD + was detected at a very low intensity (<5000 counts) causing a large measurement variance (CV(QC) = 29%).…”

Section: Resultsmentioning

confidence: 80%

Untargeted metabolomics reveals a mild impact of remote ischemic conditioning on the plasma metabolome and α-hydroxybutyrate as a possible cardioprotective factor and biomarker of tissue ischemia

et al. 2017

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IntroductionRemote ischemic conditioning (RIC) is a maneuver by which short non-lethal ischemic events are applied on distant organs or limbs to reduce ischemia and reperfusion injuries caused by e.g. myocardial infarct. Although intensively investigated, the specific mechanism of this protective phenomenon remains incompletely understood and in particular, knowledge on the role of small metabolites is scarce.ObjectivesIn this study, we aimed to study perturbations in the plasma metabolome following RIC and gain insight into metabolic changes by the intervention as well as to identify potential novel cardio-protective metabolites.MethodsBlood plasma samples from ten healthy males were collected prior to and after RIC and tested for bioactivity in a HL-1 based cellular model of ischemia–reperfusion damage. Following this, the plasma was analyzed using untargeted LC-qTOF-MS and regulated metabolites were identified using univariate and multivariate statistical analysis. Results were finally verified in a second plasma study from the same group of volunteers and by testing a metabolite ester in the HL-1 cell model.ResultsThe analysis revealed a moderate impact on the plasma metabolome following RIC. One metabolite, α-hydroxybutyrate (AHB) however, stood out as highly significantly upregulated after RIC. AHB might be a novel and more sensitive plasma-biomarker of transient tissue ischemia than lactate. Importantly, it was also found that a cell permeable AHB precursor protects cardiomyocytes from ischemia–reperfusion damage.ConclusionUntargeted metabolomics analysis of plasma following RIC has led to insight into metabolism during RIC and revealed a possible novel metabolite of relevance to ischemic-reperfusion damage.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-017-1202-2) contains supplementary material, which is available to authorized users.

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“…BHMT2 converts homocysteine to methionine. Interestingly, the increase in methionine in patients with AKI has been significantly associated with mortality [26] and this metabolite was also elevated in serum in the ischemic period metabolomic study conducted with these same animals [37]. GBA3 is an enzyme that hydrolyzes various β-D-glucosides with the release of beta-D-glucose [27].…”

Section: Urinary Proteomementioning

confidence: 98%

“…Um dos produtos da degradação da homocisteína, a metionina, foi observada elevada no plasma durante o período isquêmico em nosso estudo metabolômico, bem como, associada com a mortalidade de pacientes com LRA (Sun et al 2012b;Malagrino et al 2016).…”

Section: Proteínas Do Córtex Renal Candidatas a Biomarcadoras De Lra unclassified

Metabolomic characterization of renal ischemia and reperfusion in a swine model

Cited by 16 publications

References 64 publications

Proteo-metabolomics reveals compensation between ischemic and non-injured contralateral kidneys after reperfusion

Proteo-metabolomics reveals compensation between ischemic and non-injured contralateral kidneys after reperfusion

Untargeted metabolomics reveals a mild impact of remote ischemic conditioning on the plasma metabolome and α-hydroxybutyrate as a possible cardioprotective factor and biomarker of tissue ischemia

Perfil proteômico da lesão renal aguda induzida por isquemia e reperfusão

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