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Article ; Online: Acclimation and transgenerational plasticity support increased cadmium tolerance in Gammarus populations exposed to natural metal contamination in headwater streams

Lalouette, Auréline / Esposti, Davide Degli / Garnero, Laura / Allibert, Maxime / Dherret, Lysiane / Dabrin, Aymeric / Delorme, Nicolas / Recoura-Massaquant, Rémi / Chaumot, Arnaud

Science of the Total Environment. 2023 Aug. 09, p.166216-

2023 , Page(s) 166216–

Abstract: Considering long-term population effects of chronic exposure to contaminants remains limited in ecological risk assessment. Field evidence that multigenerational exposure influences organisms' sensitivity is still scarce, and mechanisms have yet to be ... ...

Abstract	Considering long-term population effects of chronic exposure to contaminants remains limited in ecological risk assessment. Field evidence that multigenerational exposure influences organisms' sensitivity is still scarce, and mechanisms have yet to be elucidated in the environmental context. This study focuses on the crustacean Gammarus fossarum, for which an increased tolerance to cadmium (Cd) has previously been reported in a naturally low-contaminated headwater stream. Our objectives were to investigate whether Cd tolerance is a common phenomenon in headwater populations, and to elucidate the nature of the tolerance and its intergenerational transmission. For this, we carried out an in-depth in situ characterization of Cd exposure (gammarids' caging) and levels of tolerance in nine populations on a regional scale, as well as laboratory maintenance and cross-breeding of contaminated and uncontaminated populations. Acute tolerance levels correlate positively with bioavailable Cd contamination levels among streams. The contaminated and non-contaminated populations differ about two-fold in sensitivity to Cd. Tolerance was found in all age classes of contaminated populations, it can be transiently lost during the year, and it was transmissible to offspring. In addition, tolerance levels dropped significantly when organisms were transferred to a Cd-free environment for two months. These organisms also ceased producing tolerant offspring, confirming a non-genetic transmission of Cd tolerance between generations. These findings support that Cd tolerance corresponds to non-genetic acclimation combined with transgenerational plasticity. Moreover, cross-breeding revealed that tolerance transmission to offspring is not limited to maternal effect. We suggest epigenetics as a plausible mechanism for the plasticity of Cd sensitivity observed in the field. Our results therefore highlight the neglected role of plasticity and non-genetic transmission of modified sensitivities during the long-term exposure of natural populations to environmental contamination.
Keywords	Gammarus fossarum ; acclimation ; bioavailability ; cadmium ; chronic exposure ; crossing ; environment ; environmental assessment ; epigenetics ; maternal effect ; phenotypic plasticity ; plasticity ; pollution ; progeny ; streams ; water ; Amphipods ; Multigenerational exposure ; Evolution ; Adaptation ; Parental effect ; Non-genetic transmission
Language	English
Dates of publication	2023-0809
Publishing place	Elsevier B.V.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2023.166216
Database	NAL-Catalogue (AGRICOLA)

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Article: Co-expression network analysis identifies novel molecular pathways associated with cadmium and pyriproxyfen testicular toxicity in Gammarus fossarum

Koenig, Natacha / Almunia, Christine / Bonnal-Conduzorgues, Aurore / Armengaud, Jean / Chaumot, Arnaud / Geffard, Olivier / Esposti, Davide Degli

Aquatic toxicology. 2021 June, v. 235

2021

Abstract: Omics approaches are continuously providing new clues on the mechanisms of action of contaminants in species of environmental relevance, contributing to the emergence of molecular ecotoxicology. Co-expression network approaches represent a suitable ... ...

Abstract	Omics approaches are continuously providing new clues on the mechanisms of action of contaminants in species of environmental relevance, contributing to the emergence of molecular ecotoxicology. Co-expression network approaches represent a suitable methodological framework for studying the rich content of omics datasets. This study aimed to find evidence of key pathways and proteins related to the testicular toxicity in the sentinel crustacean species Gammarus fossarum exposed to endocrine disruptors using a weighted protein co-expression network analysis. From a shotgun proteomics dataset of male gonads of G. fossarum organisms exposed to cadmium (Cd), pyriproxyfen (Pyr) and methoxyfenozide (Met) in laboratory conditions, four distinct modules were identified as significantly correlated to contaminants’ exposure. Protein set enrichment analysis identified modules involved in cytoskeleton organization and oxidative stress response associated with the Cd exposure. The module associated with Pyr exposure was associated with endoplasmic reticulum stress (ER) response, and the module correlated with Met exposure was characterized by a significant proportion of amphipod-restricted proteins whose functions are still not characterized. Our results show that co-expression networks are efficient and adapted tools to identify new potential mode of actions from environmental sentinel species, such as G. fossarum, using a proteogenomic approach, even without an annotated genome.
Keywords	Gammarus fossarum ; cadmium ; cytoskeleton ; data collection ; ecotoxicology ; endoplasmic reticulum stress ; genome ; indicator species ; males ; methoxyfenozide ; oxidative stress ; proteomics ; pyriproxyfen ; stress response ; testes ; toxicity
Language	English
Dates of publication	2021-06
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	782699-0
ISSN	1879-1514 ; 0166-445X
ISSN (online)	1879-1514
ISSN	0166-445X
DOI	10.1016/j.aquatox.2021.105816
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Article ; Online: Co-expression network analysis identifies novel molecular pathways associated with cadmium and pyriproxyfen testicular toxicity in Gammarus fossarum.

Koenig, Natacha / Almunia, Christine / Bonnal-Conduzorgues, Aurore / Armengaud, Jean / Chaumot, Arnaud / Geffard, Olivier / Esposti, Davide Degli

Aquatic toxicology (Amsterdam, Netherlands)

2021 Volume 235, Page(s) 105816

Abstract	Omics approaches are continuously providing new clues on the mechanisms of action of contaminants in species of environmental relevance, contributing to the emergence of molecular ecotoxicology. Co-expression network approaches represent a suitable methodological framework for studying the rich content of omics datasets. This study aimed to find evidence of key pathways and proteins related to the testicular toxicity in the sentinel crustacean species Gammarus fossarum exposed to endocrine disruptors using a weighted protein co-expression network analysis. From a shotgun proteomics dataset of male gonads of G. fossarum organisms exposed to cadmium (Cd), pyriproxyfen (Pyr) and methoxyfenozide (Met) in laboratory conditions, four distinct modules were identified as significantly correlated to contaminants' exposure. Protein set enrichment analysis identified modules involved in cytoskeleton organization and oxidative stress response associated with the Cd exposure. The module associated with Pyr exposure was associated with endoplasmic reticulum stress (ER) response, and the module correlated with Met exposure was characterized by a significant proportion of amphipod-restricted proteins whose functions are still not characterized. Our results show that co-expression networks are efficient and adapted tools to identify new potential mode of actions from environmental sentinel species, such as G. fossarum, using a proteogenomic approach, even without an annotated genome.
MeSH term(s)	Amphipoda/metabolism ; Amphipoda/physiology ; Animals ; Cadmium/toxicity ; Ecotoxicology/methods ; Endocrine Disruptors/toxicity ; Genome ; Hydrazines ; Juvenile Hormones ; Male ; Proteomics/methods ; Pyridines/toxicity ; Sentinel Species/genetics ; Testis/drug effects ; Water Pollutants, Chemical/toxicity
Chemical Substances	Endocrine Disruptors ; Hydrazines ; Juvenile Hormones ; Pyridines ; Water Pollutants, Chemical ; Cadmium (00BH33GNGH) ; pyriproxyfen (3Q9VOR705O) ; methoxyfenozide (62A22651ZX)
Language	English
Publishing date	2021-03-26
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	782699-0
ISSN	1879-1514 ; 0166-445X
ISSN (online)	1879-1514
ISSN	0166-445X
DOI	10.1016/j.aquatox.2021.105816
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Article ; Online: Gate-Controlled Suspended Titanium Nanobridge Supercurrent Transistor.

Rocci, Mirko / De Simoni, Giorgio / Puglia, Claudio / Esposti, Davide Degli / Strambini, Elia / Zannier, Valentina / Sorba, Lucia / Giazotto, Francesco

ACS nano

2020 Volume 14, Issue 10, Page(s) 12621–12628

Abstract: Under standard conditions, the electrostatic field-effect is negligible in conventional metals and was expected to be completely ineffective also in superconducting metals. This common belief was recently put under question by a family of experiments ... ...

Abstract	Under standard conditions, the electrostatic field-effect is negligible in conventional metals and was expected to be completely ineffective also in superconducting metals. This common belief was recently put under question by a family of experiments that displayed full gate-voltage-induced suppression of critical current in superconducting all-metallic gated nanotransistors. To date, the microscopic origin of this phenomenon is under debate, and trivial explanations based on heating effects given by the negligible electron leakage from the gates should be excluded. Here, we demonstrate the control of the supercurrent in fully suspended superconducting nanobridges. Our advanced nanofabrication methods allow us to build suspended superconducting Ti-based supercurrent transistors which show ambipolar and monotonic full suppression of the critical current for gate voltages of
Language	English
Publishing date	2020-08-28
Publishing country	United States
Document type	Journal Article
ISSN	1936-086X
ISSN (online)	1936-086X
DOI	10.1021/acsnano.0c05355
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Article: HPV Infection Leaves a DNA Methylation Signature in Oropharyngeal Cancer Affecting Both Coding Genes and Transposable Elements.

Camuzi, Diego / Buexm, Luisa Aguirre / Lourenço, Simone de Queiroz Chaves / Esposti, Davide Degli / Cuenin, Cyrille / Lopes, Monique de Souza Almeida / Manara, Francesca / Talukdar, Fazlur Rahman / Herceg, Zdenko / Ribeiro Pinto, Luis Felipe / Soares-Lima, Sheila Coelho

Cancers

2021 Volume 13, Issue 14

Abstract: HPV oncoproteins can modulate DNMT1 expression and activity, and previous studies have reported both gene-specific and global DNA methylation alterations according to HPV status in head and neck cancer. However, validation of these findings and a more ... ...

Abstract	HPV oncoproteins can modulate DNMT1 expression and activity, and previous studies have reported both gene-specific and global DNA methylation alterations according to HPV status in head and neck cancer. However, validation of these findings and a more detailed analysis of the transposable elements (TEs) are still missing. Here we performed pyrosequencing to evaluate a 5-CpG methylation signature and Line1 methylation in an oropharyngeal squamous cell carcinoma (OPSCC) cohort. We further evaluated the methylation levels of the TEs, their correlation with gene expression and their impact on overall survival (OS) using the TCGA cohort. In our dataset, the 5-CpG signature distinguished HPV-positive and HPV-negative OPSCC with 66.67% sensitivity and 84.33% specificity. Line1 methylation levels were higher in HPV-positive cases. In the TCGA cohort, Line1, Alu and long terminal repeats (LTRs) showed hypermethylation in a frequency of 60.5%, 58.9% and 92.3%, respectively.
Language	English
Publishing date	2021-07-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13143621
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Article ; Online: A transcriptomic analysis of black cohosh: Actein alters cholesterol biosynthesis pathways and synergizes with simvastatin.

Einbond, Linda Saxe / Soffritti, Morando / Esposti, Davide Degli / Wu, Hsan-Au / Balick, Michael / Ma, Hongbao / Redenti, Stephen / Roter, Alan

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

2018 Volume 120, Page(s) 356–366

Abstract: Previous studies indicate that the herb black cohosh (Actaea racemosa L.) and the triterpene glycoside actein inhibit the growth of human breast cancer cells and activate stress-associated responses. This study assessed the transcriptomic effects of ... ...

Abstract	Previous studies indicate that the herb black cohosh (Actaea racemosa L.) and the triterpene glycoside actein inhibit the growth of human breast cancer cells and activate stress-associated responses. This study assessed the transcriptomic effects of black cohosh and actein on rat liver tissue, using Ingenuity and ToxFX analyses. Sprague-Dawley rats were treated with an extract of black cohosh enriched in triterpene glycosides (27%) for 24 h or actein for 6 and 24 h, at 35.7 mg/kg, and liver tissue collected for gene expression analysis. Ingenuity analysis indicates the top canonical pathways are, for black cohosh, RAR Activation, and, for actein, Superpathway of Cholesterol Biosynthesis, at 24 h. Actein alters the expression of cholesterol biosynthetic genes, but does not inhibit HMG-CoA reductase activity. Black cohosh and actein inhibited the growth of human breast and colon cancer cells and synergized with the statin simvastatin. Combinations of black cohosh with certain classes of statins could enhance their activity, as well as toxic, such as inflammatory liver, side effects. Transcriptomic analysis indicates black cohosh and actein warrant further study to prevent and treat cancer and lipid disorders. This study lays the basis for an approach to characterize the mode of action and toxicity of herbal medicines.
MeSH term(s)	Animals ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cholesterol/biosynthesis ; Cimicifuga/chemistry ; Cimicifuga/genetics ; Colonic Neoplasms/pathology ; Dose-Response Relationship, Drug ; Drug Synergism ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Rats ; Real-Time Polymerase Chain Reaction ; Saponins/pharmacology ; Signal Transduction ; Simvastatin/pharmacology ; Transcriptome ; Triterpenes/pharmacology
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Saponins ; Triterpenes ; Cholesterol (97C5T2UQ7J) ; Simvastatin (AGG2FN16EV) ; actein (I14QO4LW9V)
Language	English
Publishing date	2018-06-30
Publishing country	England
Document type	Journal Article
ZDB-ID	782617-5
ISSN	1873-6351 ; 0278-6915
ISSN (online)	1873-6351
ISSN	0278-6915
DOI	10.1016/j.fct.2018.06.064
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Article: Antiproliferative Effects of Epigenetic Modifier Drugs Through E-cadherin Up-regulation in Liver Cancer Cell Lines.

Uribe, Diego / Cardona, Andres / Esposti, Davide Degli / Cros, Marie-Pierre / Cuenin, Cyrille / Herceg, Zdenko / Camargo, Mauricio / Cortés-Mancera, Fabian M

Annals of hepatology

2018 Volume 17, Issue 3, Page(s) 444–460

Abstract: Introduction and aim: Epigenetic alterations play an essential role in cancer onset and progression, thus studies of drugs targeting the epigenetic machinery are a principal concern for cancer treatment. Here, we evaluated the potential of the ... ...

Abstract	Introduction and aim: Epigenetic alterations play an essential role in cancer onset and progression, thus studies of drugs targeting the epigenetic machinery are a principal concern for cancer treatment. Here, we evaluated the potential of the combination of the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5aza-dC) and the pan-deacetylase inhibitor Trichostatin A (TSA), at low cytotoxic concentrations, to modulate the canonical Wnt/β-catenin pathway in liver cancer cells. Material and methods: Pyrosequencing was used for DNA methylation analyses of LINE-1 sequences and the Wnt/β-catenin pathway antagonist DKK3, SFRP1, WIF1 and CDH1. qRT-PCR was employed to verify the expression of the antagonist. Pathway regulation were evaluated looking at the expression of β-catenin and E-cadherin by confocal microscopy and the antitumoral effects of the drugs was studied by wound healing and clonogenic assays. Results: Our result suggest that 5aza-dC and TSA treatments were enough to induce a significant expression of the pathway antagonists, decrease of β-catenin protein levels, re-localization of the protein to the plasma membrane, and pathway transcriptional activity reduction. These important effects exerted an antitumoral outcome shown by the reduction of the migration and clonogenic capabilities of the cells. Conclusion: We were able to demonstrate Wnt/ β-catenin pathway modulation through E-cadherin up-regulation induced by 5aza-dC and TSA treatments, under an activation-pathway background, like CTNNB1 and TP53 mutations. These findings provide evidences of the potential effect of epigenetic modifier drugs for liver cancer treatment. However, further research needs to be conducted, to determine the in vivo potential of this treatment regimen for the management of liver cancer.
MeSH term(s)	Antigens, CD/genetics ; Antigens, CD/metabolism ; Antimetabolites, Antineoplastic/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Cadherins/genetics ; Cadherins/metabolism ; Carcinoma, Hepatocellular/drug therapy ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Cell Proliferation/drug effects ; Cell Proliferation/genetics ; DNA Methylation/drug effects ; DNA Modification Methylases/antagonists & inhibitors ; DNA Modification Methylases/metabolism ; Decitabine/pharmacology ; Enzyme Inhibitors/pharmacology ; Epigenesis, Genetic/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Hep G2 Cells ; Humans ; Hydroxamic Acids/pharmacology ; Liver Neoplasms/drug therapy ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Mutation ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism ; Up-Regulation ; Wnt Signaling Pathway/drug effects ; Wnt Signaling Pathway/genetics ; beta Catenin/genetics ; beta Catenin/metabolism
Chemical Substances	Antigens, CD ; Antimetabolites, Antineoplastic ; CDH1 protein, human ; CTNNB1 protein, human ; Cadherins ; Enzyme Inhibitors ; Hydroxamic Acids ; TP53 protein, human ; Tumor Suppressor Protein p53 ; beta Catenin ; trichostatin A (3X2S926L3Z) ; Decitabine (776B62CQ27) ; DNA Modification Methylases (EC 2.1.1.-)
Language	English
Publishing date	2018-04-09
Publishing country	Mexico
Document type	Journal Article
ZDB-ID	2188733-0
ISSN	1665-2681
ISSN	1665-2681
DOI	10.5604/01.3001.0011.7389
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Article ; Online: Non-alcoholic steatohepatitis: new insights from OMICS studies.

Martel, Cecile / Esposti, Davide Degli / Bouchet, Antonin / Brenner, Catherine / Lemoine, Antoinette

Current pharmaceutical biotechnology

2011 Volume 13, Issue 5, Page(s) 726–735

Abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common liver pathology characterized by fat accumulation in a context of metabolic syndrome or insulin resistance. It can be associated with obesity, diabetes, hyperinsulinemia, dyslipidemia as well ... ...

Abstract	Non-alcoholic fatty liver disease (NAFLD) is the most common liver pathology characterized by fat accumulation in a context of metabolic syndrome or insulin resistance. It can be associated with obesity, diabetes, hyperinsulinemia, dyslipidemia as well as hypertension. NAFLD consists of a large spectrum of hepatic lesions including benign steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis or hepatocellular carcinoma. Upon chronic stress, NASH would occur via at least "two-hits" process involving modulation of a high number of genes and proteins. Firstly, the accumulation of fat, either due to the increased inflow of free fatty acids or de novo lipogenesis, leads to steatosis. Secondly, when adaptive mechanisms for stress tolerance are overwhelmed, lipotoxicity and chronic inflammation trigger major hepatic damages, mainly via oxidative and inflammatory stress, lipid peroxidation and cell death. As a consequence, all these processes concur to favor steatohepatitis, fibrosis and cancer. Recently, the elucidation of physiopathological signaling cascades controlling NAFLD and NASH benefited from large-scale studies, namely the omics, such as transcriptomics, genomics, proteomics, and lipidomics. The advent of lipidomics would allow shedding light upon the respective roles of triglyceride and fatty acid metabolites in the lipotoxic liver injury hypothesis for the pathogenesis of NASH. In this review, the contribution of the omics to the understanding of the molecular basis of NASH is discussed that could offer perspectives for novel biomarkers discovery.
MeSH term(s)	Animals ; Fatty Liver/genetics ; Fatty Liver/metabolism ; Humans ; Non-alcoholic Fatty Liver Disease
Language	English
Publishing date	2011-12-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2132197-8
ISSN	1873-4316 ; 1389-2010
ISSN (online)	1873-4316
ISSN	1389-2010
DOI	10.2174/138920112799857558
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Article ; Online: Identification of novel long non-coding RNAs deregulated in hepatocellular carcinoma using RNA-sequencing.

Esposti, Davide Degli / Hernandez-Vargas, Hector / Voegele, Catherine / Fernandez-Jimenez, Nora / Forey, Nathalie / Bancel, Brigitte / Le Calvez-Kelm, Florence / McKay, James / Merle, Philippe / Herceg, Zdenko

Oncotarget

2016 Volume 7, Issue 22, Page(s) 31862–31877

Abstract: Functional characterization of long non-coding RNAs (lncRNAs) and their pathological relevance is still a challenging task. Abnormal expression of a few long non-coding RNAs have been found associated with hepatocellular carcinoma, with potential ... ...

Abstract	Functional characterization of long non-coding RNAs (lncRNAs) and their pathological relevance is still a challenging task. Abnormal expression of a few long non-coding RNAs have been found associated with hepatocellular carcinoma, with potential implications to both improve our understanding of molecular mechanism of liver carcinogenesis and to discover biomarkers for early diagnosis or therapy. However, the understanding of the global role of lncRNAs during HCC development is still in its infancy. In this study, we produced RNA-Seq data from 23 liver tissues (controls, cirrhotic and HCCs) and applied statistical and gene network analysis approaches to identify and characterize expressed lncRNAs. We detected 5,525 lncRNAs across different tissue types and identified 57 differentially expressed lncRNAs in HCC compared with adjacent non-tumour tissues using stringent criteria (FDR<0.05, Fold Change>2). Using weighted gene co-expression network analysis (WGCNA), we found that differentially expressed lncRNAs are co-expressed with genes involved in cell cycle regulation, TGF-β signalling and liver metabolism. Furthermore, we found that more than 20% of differentially expressed lncRNAs are associated to actively transcribed enhancers and that the co-expression patterns with their closest genes change dramatically during HCC development. Our study provides the most comprehensive compendium of lncRNAs expressed in HCC, as well as in control or cirrhotic livers. Our results identified both known oncogenic lncRNAs (such as H19 and CRNDE) and novel lncRNAs involved in cell cycle deregulation and liver metabolism deficits occurring during HCC development.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/metabolism ; Carcinoma, Hepatocellular/pathology ; Female ; Gene Expression Profiling/methods ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Liver Neoplasms/genetics ; Liver Neoplasms/metabolism ; Liver Neoplasms/pathology ; Male ; Middle Aged ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; RNA, Neoplasm/genetics ; RNA, Neoplasm/metabolism ; Sequence Analysis, RNA ; Signal Transduction ; Transcriptome
Chemical Substances	Biomarkers, Tumor ; RNA, Long Noncoding ; RNA, Neoplasm
Language	English
Publishing date	2016-02-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.7364
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Article ; Online: Ischemic Postconditioning of the Liver Graft in Adult Liver Transplantation.

Ricca, Luana / Lemoine, Antoinette / Cauchy, François / Hamelin, Jocelyne / Sebagh, Mylène / Esposti, Davide Degli / Salloum, Chady / Vibert, Eric / Balducci, Genoveffa / Azoulay, Daniel

Transplantation

2015 Volume 99, Issue 8, Page(s) 1633–1643

Abstract: Background: Ischemia-reperfusion (I/R) injury is the main cause of graft failure in liver transplantation (LT). Ischemic postconditioning (IPo) has shown to be beneficial against I/R injury. Our objective was to compare the results of LT with or without ...

Abstract	Background: Ischemia-reperfusion (I/R) injury is the main cause of graft failure in liver transplantation (LT). Ischemic postconditioning (IPo) has shown to be beneficial against I/R injury. Our objective was to compare the results of LT with or without IPo. Methods: One hundred patients undergoing LT alternatively received IPo or not. At the time of arterial reperfusion, IPo consisted of three 1-minute arterial occlusions, interspersed with 1-minute reperfusion pauses. The primary endpoint was postoperative aspartate aminotransferase (AST) peak value; early graft dysfunction and histological I/R injury were secondary endpoints. Results: Median postoperative AST peak values was similar in both groups (426 vs 463 IU/L, P = 0.21); no difference was found in other postoperative liver function tests. In the IPo group, fewer grafts presented severe histological I/R injury (12% vs 28%; P = 0.029). Ischemic postconditioning did not induce changes in cellular apoptosis but triggered autophagy in periportal areas. Independent predictors of severe I/R injury were IPo (odds ratio, 0.20; P = 0.008) and arterial warm ischemia duration (odds ratio, 1.05; P = 0.008). Early graft dysfunction rate was similar in both groups (20% versus 26%, P = 0.47) and was associated with severe histological I/R injury and longer cold ischemia. Morbidity, mortality, and 1-year graft and patient survival were similar in both groups. Conclusions: Ischemic postconditioning did not influence postoperative AST peak values or other liver function tests. However, our results showed a better tolerance to I/R injury on histological findings of grafts receiving IPo. Future studies are necessary to optimize the IPo protocol in LT, to clarify its clinical impact, and to deepen the molecular understanding.
MeSH term(s)	Adult ; Aged ; Aspartate Aminotransferases/blood ; Biomarkers/blood ; Biopsy ; Cold Ischemia/adverse effects ; Female ; France ; Graft Survival ; Humans ; Ischemic Postconditioning/adverse effects ; Ischemic Postconditioning/methods ; Ischemic Postconditioning/mortality ; Kaplan-Meier Estimate ; Liver Function Tests ; Liver Transplantation/adverse effects ; Liver Transplantation/methods ; Liver Transplantation/mortality ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Predictive Value of Tests ; Primary Graft Dysfunction/diagnosis ; Primary Graft Dysfunction/etiology ; Primary Graft Dysfunction/mortality ; Primary Graft Dysfunction/prevention & control ; Risk Factors ; Time Factors ; Treatment Outcome
Chemical Substances	Biomarkers ; Aspartate Aminotransferases (EC 2.6.1.1)
Language	English
Publishing date	2015-08
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000000685
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In stock of ZB MED Cologne/Königswinter

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Kategorien

In stock of ZB MED Cologne/Königswinter

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More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito