Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations
Oxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was designed to ascertain whether an oxidant/antioxidant imbalance i...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/11/2/231 |
| _version_ | 1827657534954012672 |
|---|---|
| author | Marianna Miliaraki Panagiotis Briassoulis Stavroula Ilia Kalliopi Michalakakou Theodoros Karakonstantakis Aikaterini Polonifi Kalliopi Bastaki Efrossini Briassouli Konstantinos Vardas Aikaterini Pistiki Maria Theodorakopoulou Theonymfi Tavladaki Anna-Maria Spanaki Eumorfia Kondili Helen Dimitriou Maria Venihaki Sotirios Tsiodras Dimitrios Georgopoulos Marina Mantzourani Serafeim Nanas Apostolos Armaganidis George L. Daikos Ioannis Papassotiriou George Briassoulis |
| author_facet | Marianna Miliaraki Panagiotis Briassoulis Stavroula Ilia Kalliopi Michalakakou Theodoros Karakonstantakis Aikaterini Polonifi Kalliopi Bastaki Efrossini Briassouli Konstantinos Vardas Aikaterini Pistiki Maria Theodorakopoulou Theonymfi Tavladaki Anna-Maria Spanaki Eumorfia Kondili Helen Dimitriou Maria Venihaki Sotirios Tsiodras Dimitrios Georgopoulos Marina Mantzourani Serafeim Nanas Apostolos Armaganidis George L. Daikos Ioannis Papassotiriou George Briassoulis |
| author_sort | Marianna Miliaraki |
| collection | DOAJ |
| description | Oxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was designed to ascertain whether an oxidant/antioxidant imbalance is an independent sepsis discriminator and mortality predictor in intensive care unit (ICU) patients with sepsis (<i>n</i> = 145), compared to non-infectious critically ill patients (<i>n</i> = 112) and healthy individuals (<i>n</i> = 89). Serum total oxidative status (TOS) and total antioxidant capacity (TAC) were measured by photometric testing. IL-6, -8, -10, -27, Hsp72/90 (ELISA), and selected antioxidant biomolecules (Ζn, glutathione) were correlated with apoptotic mediators (caspase-3, capsase-9) and the central anti-apoptotic survivin protein (ELISA, real-time PCR). A wide scattering of TOS, TAC, and TOS/TAC in all three groups was demonstrated. Septic patients had an elevated TOS/TAC, compared to non-infectious critically ill patients and healthy individuals (<i>p</i> = 0.001). TOS/TAC was associated with severity scores, procalcitonin, IL-6, -10, -27, IFN-γ, Hsp72, Hsp90, survivin protein, and survivin isoforms -2B, -ΔΕx3, -WT (<i>p</i> < 0.001). In a propensity probability (age-sex-adjusted) logistic regression model, only sepsis was independently associated with TOS/TAC (Exp(B) 25.4, <i>p</i> < 0.001). The AUC<sub>TOS/TAC</sub> (0.96 (95% CI = 0.93–0.99)) was higher than AUC<sub>TAC</sub> (z = 20, <i>p</i> < 0.001) or AUC<sub>TOS</sub> (z = 3.1, <i>p</i> = 0.002) in distinguishing sepsis. TOS/TAC, TOS, survivin isoforms -WT and -2B, Hsp90, IL-6, survivin protein, and repressed TAC were strong predictors of mortality (<i>p</i> < 0.01). Oxidant/antioxidant status is impaired in septic compared to critically ill patients with trauma or surgery and is related to anti-apoptotic, inflammatory, and innate immunity alterations. The unpredicted TOS/TAC imbalance might be related to undefined phenotypes in patients and healthy individuals. |
| first_indexed | 2024-03-09T22:46:01Z |
| format | Article |
| id | doaj.art-f7a9bcd4c64e4abebbff5bbc3bf187cb |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T22:46:01Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-f7a9bcd4c64e4abebbff5bbc3bf187cb2023-11-23T18:30:29ZengMDPI AGAntioxidants2076-39212022-01-0111223110.3390/antiox11020231Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity AlterationsMarianna Miliaraki0Panagiotis Briassoulis1Stavroula Ilia2Kalliopi Michalakakou3Theodoros Karakonstantakis4Aikaterini Polonifi5Kalliopi Bastaki6Efrossini Briassouli7Konstantinos Vardas8Aikaterini Pistiki9Maria Theodorakopoulou10Theonymfi Tavladaki11Anna-Maria Spanaki12Eumorfia Kondili13Helen Dimitriou14Maria Venihaki15Sotirios Tsiodras16Dimitrios Georgopoulos17Marina Mantzourani18Serafeim Nanas19Apostolos Armaganidis20George L. Daikos21Ioannis Papassotiriou22George Briassoulis23Pediatric Intensive Care Unit, University Hospital of Heraklion and School of Medicine, University of Crete, 71110 Heraklion, GreecePediatric Intensive Care Unit, University Hospital of Heraklion and School of Medicine, University of Crete, 71110 Heraklion, GreecePediatric Intensive Care Unit, University Hospital of Heraklion and School of Medicine, University of Crete, 71110 Heraklion, GreeceDepartment of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, 11527 Athens, GreeceDepartment of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, 11527 Athens, GreeceFirst Department of Internal Medicine-Propaedeutic, National and Kapodistrian University of Athens, 11527 Athens, GreecePediatric Intensive Care Unit, University Hospital of Heraklion and School of Medicine, University of Crete, 71110 Heraklion, GreeceFirst Department of Internal Medicine-Propaedeutic, National and Kapodistrian University of Athens, 11527 Athens, GreeceFirst Critical Care Department, Evangelismos University Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece4th Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece2nd Department of Critical Care, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, GreecePediatric Intensive Care Unit, University Hospital of Heraklion and School of Medicine, University of Crete, 71110 Heraklion, GreecePediatric Intensive Care Unit, University Hospital of Heraklion and School of Medicine, University of Crete, 71110 Heraklion, GreeceDepartment of Intensive Care Medicine, University Hospital of Heraklion and Medical School, University of Crete, 71110 Heraklion, GreeceLaboratory of Child Health, School of Medicine, University of Crete, 71003 Heraklion, GreeceDepartment of Clinical Chemistry, School of Medicine, University of Crete, 71003 Heraklion, Greece4th Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Athens, GreeceDepartment of Intensive Care Medicine, University Hospital of Heraklion and Medical School, University of Crete, 71110 Heraklion, GreeceFirst Department of Internal Medicine-Propaedeutic, National and Kapodistrian University of Athens, 11527 Athens, GreeceFirst Critical Care Department, Evangelismos University Hospital, National and Kapodistrian University of Athens, 10676 Athens, Greece2nd Department of Critical Care, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, GreeceFirst Department of Internal Medicine-Propaedeutic, National and Kapodistrian University of Athens, 11527 Athens, GreeceDepartment of Clinical Biochemistry, “Aghia Sophia” Children’s Hospital, 11527 Athens, GreecePediatric Intensive Care Unit, University Hospital of Heraklion and School of Medicine, University of Crete, 71110 Heraklion, GreeceOxidative stress is considered pivotal in the pathophysiology of sepsis. Oxidants modulate heat shock proteins (Hsp), interleukins (IL), and cell death pathways, including apoptosis. This multicenter prospective observational study was designed to ascertain whether an oxidant/antioxidant imbalance is an independent sepsis discriminator and mortality predictor in intensive care unit (ICU) patients with sepsis (<i>n</i> = 145), compared to non-infectious critically ill patients (<i>n</i> = 112) and healthy individuals (<i>n</i> = 89). Serum total oxidative status (TOS) and total antioxidant capacity (TAC) were measured by photometric testing. IL-6, -8, -10, -27, Hsp72/90 (ELISA), and selected antioxidant biomolecules (Ζn, glutathione) were correlated with apoptotic mediators (caspase-3, capsase-9) and the central anti-apoptotic survivin protein (ELISA, real-time PCR). A wide scattering of TOS, TAC, and TOS/TAC in all three groups was demonstrated. Septic patients had an elevated TOS/TAC, compared to non-infectious critically ill patients and healthy individuals (<i>p</i> = 0.001). TOS/TAC was associated with severity scores, procalcitonin, IL-6, -10, -27, IFN-γ, Hsp72, Hsp90, survivin protein, and survivin isoforms -2B, -ΔΕx3, -WT (<i>p</i> < 0.001). In a propensity probability (age-sex-adjusted) logistic regression model, only sepsis was independently associated with TOS/TAC (Exp(B) 25.4, <i>p</i> < 0.001). The AUC<sub>TOS/TAC</sub> (0.96 (95% CI = 0.93–0.99)) was higher than AUC<sub>TAC</sub> (z = 20, <i>p</i> < 0.001) or AUC<sub>TOS</sub> (z = 3.1, <i>p</i> = 0.002) in distinguishing sepsis. TOS/TAC, TOS, survivin isoforms -WT and -2B, Hsp90, IL-6, survivin protein, and repressed TAC were strong predictors of mortality (<i>p</i> < 0.01). Oxidant/antioxidant status is impaired in septic compared to critically ill patients with trauma or surgery and is related to anti-apoptotic, inflammatory, and innate immunity alterations. The unpredicted TOS/TAC imbalance might be related to undefined phenotypes in patients and healthy individuals.https://www.mdpi.com/2076-3921/11/2/231oxidative stressantioxidant statusapoptosisinterleukinsheat shock proteinsTOS |
| spellingShingle | Marianna Miliaraki Panagiotis Briassoulis Stavroula Ilia Kalliopi Michalakakou Theodoros Karakonstantakis Aikaterini Polonifi Kalliopi Bastaki Efrossini Briassouli Konstantinos Vardas Aikaterini Pistiki Maria Theodorakopoulou Theonymfi Tavladaki Anna-Maria Spanaki Eumorfia Kondili Helen Dimitriou Maria Venihaki Sotirios Tsiodras Dimitrios Georgopoulos Marina Mantzourani Serafeim Nanas Apostolos Armaganidis George L. Daikos Ioannis Papassotiriou George Briassoulis Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations Antioxidants oxidative stress antioxidant status apoptosis interleukins heat shock proteins TOS |
| title | Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations |
| title_full | Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations |
| title_fullStr | Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations |
| title_full_unstemmed | Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations |
| title_short | Oxidant/Antioxidant Status Is Impaired in Sepsis and Is Related to Anti-Apoptotic, Inflammatory, and Innate Immunity Alterations |
| title_sort | oxidant antioxidant status is impaired in sepsis and is related to anti apoptotic inflammatory and innate immunity alterations |
| topic | oxidative stress antioxidant status apoptosis interleukins heat shock proteins TOS |
| url | https://www.mdpi.com/2076-3921/11/2/231 |
| work_keys_str_mv | AT mariannamiliaraki oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT panagiotisbriassoulis oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT stavroulailia oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT kalliopimichalakakou oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT theodoroskarakonstantakis oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT aikaterinipolonifi oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT kalliopibastaki oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT efrossinibriassouli oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT konstantinosvardas oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT aikaterinipistiki oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT mariatheodorakopoulou oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT theonymfitavladaki oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT annamariaspanaki oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT eumorfiakondili oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT helendimitriou oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT mariavenihaki oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT sotiriostsiodras oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT dimitriosgeorgopoulos oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT marinamantzourani oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT serafeimnanas oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT apostolosarmaganidis oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT georgeldaikos oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT ioannispapassotiriou oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations AT georgebriassoulis oxidantantioxidantstatusisimpairedinsepsisandisrelatedtoantiapoptoticinflammatoryandinnateimmunityalterations |