PMID- 37107247
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230430
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 12
IP  - 4
DP  - 2023 Apr 3
TI  - Hypoxia Enhances Oxidative Stress in Neutrophils from ZZ Alpha-1 Antitrypsin 
      Deficiency Patients.
LID - 10.3390/antiox12040872 [doi]
LID - 872
AB  - Alpha-1 antitrypsin deficiency (AATD) is a neutrophilic inflammatory disorder 
      that may result in local hypoxia, reactive oxygen and nitrogen species (ROS/RNS) 
      production, and increased damage in adjacent tissues. This study aims to 
      determine the impact of hypoxia on neutrophil oxidative stress profile in AATD 
      patients. Neutrophils were isolated from AATD patients and control volunteers and 
      exposed to hypoxia (1% O(2) for 4 h), ROS/RNS, mitochondrial parameters, and 
      non-enzymatic antioxidant defenses measured by flow cytometry. The expression of 
      enzymatic antioxidant defenses was determined by qRT-PCR. Our results indicate 
      that ZZ-AATD neutrophils produce higher amounts of hydrogen peroxide, 
      peroxynitrite, and nitric oxide and decreased levels of the antioxidant enzymes 
      catalase, superoxide dismutase, and glutathione reductase. Likewise, our results 
      show a decrease in mitochondrial membrane potential, indicating that this 
      organelle could be involved in the production of the reactive species observed. 
      No decrease in glutathione and thiol levels were observed. The accumulation of 
      substances with high oxidative capacity would explain the greater oxidative 
      damage observed in proteins and lipids. In conclusion, our results indicate that, 
      compared to MM control individuals, ZZ-AATD neutrophils show increased ROS/RNS 
      production under hypoxic conditions opening a new rationale for using antioxidant 
      therapies to treat the disease.
FAU - Magallon, Maria
AU  - Magallon M
AD  - School of Medicine, Department of Physiology, University of Valencia, Avda. 
      Blasco Ibanez, 15, 46010 Valencia, Spain.
AD  - IIS INCLIVA, Rare Respiratory Diseases Group, Avda. Menendez y Pelayo, 4, 46010 
      Valencia, Spain.
FAU - Castillo-Corullon, Silvia
AU  - Castillo-Corullon S
AUID- ORCID: 0000-0002-0121-2676
AD  - IIS INCLIVA, Rare Respiratory Diseases Group, Avda. Menendez y Pelayo, 4, 46010 
      Valencia, Spain.
AD  - Pediatrics Unit, Hospital Clinico Universitario de Valencia, Avda. Blasco Ibanez, 
      17, 46010 Valencia, Spain.
AD  - School of Medicine, Department of Paediatrics, University of Valencia, Avda. 
      Blasco Ibanez, 15, 46010 Valencia, Spain.
FAU - Banuls, Lucia
AU  - Banuls L
AD  - School of Medicine, Department of Physiology, University of Valencia, Avda. 
      Blasco Ibanez, 15, 46010 Valencia, Spain.
AD  - IIS INCLIVA, Rare Respiratory Diseases Group, Avda. Menendez y Pelayo, 4, 46010 
      Valencia, Spain.
FAU - Pellicer, Daniel
AU  - Pellicer D
AUID- ORCID: 0000-0002-3285-2609
AD  - School of Medicine, Department of Physiology, University of Valencia, Avda. 
      Blasco Ibanez, 15, 46010 Valencia, Spain.
AD  - IIS INCLIVA, Rare Respiratory Diseases Group, Avda. Menendez y Pelayo, 4, 46010 
      Valencia, Spain.
FAU - Romero, Teresa
AU  - Romero T
AD  - Pediatrics Unit, Hospital de Manises, Avda. Generalitat Valenciana, 50, 46940 
      Manises, Spain.
FAU - Martinez-Ferraro, Carlos
AU  - Martinez-Ferraro C
AD  - Pediatrics Unit, Hospital Clinico Universitario de Valencia, Avda. Blasco Ibanez, 
      17, 46010 Valencia, Spain.
FAU - Navarro-Garcia, Maria Mercedes
AU  - Navarro-Garcia MM
AD  - IIS INCLIVA, Rare Respiratory Diseases Group, Avda. Menendez y Pelayo, 4, 46010 
      Valencia, Spain.
FAU - Herrejon, Alberto
AU  - Herrejon A
AD  - Pulmonology Unit, Hospital Doctor Peset, Avda. Gaspar Aguilar, 90, 46017 
      Valencia, Spain.
FAU - Gonzalez, Cruz
AU  - Gonzalez C
AD  - IIS INCLIVA, Rare Respiratory Diseases Group, Avda. Menendez y Pelayo, 4, 46010 
      Valencia, Spain.
AD  - Pulmonology Unit, Hospital Clinico Universitario de Valencia, Avda. Blasco 
      Ibanez, 17, 46010 Valencia, Spain.
FAU - Dasi, Francisco
AU  - Dasi F
AUID- ORCID: 0000-0003-2938-2965
AD  - School of Medicine, Department of Physiology, University of Valencia, Avda. 
      Blasco Ibanez, 15, 46010 Valencia, Spain.
AD  - IIS INCLIVA, Rare Respiratory Diseases Group, Avda. Menendez y Pelayo, 4, 46010 
      Valencia, Spain.
LA  - eng
GR  - PI17/01250 grants, and European Regional Development Funds (FEDER)./Instituto de 
      Salud Carlos III/
GR  - 2017 grant/Sociedad Valenciana de Neumologia/
PT  - Journal Article
DEP - 20230403
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC10135227
OTO - NOTNLM
OT  - alpha-1 antitrypsin deficiency
OT  - chronic obstructive pulmonary disease
OT  - cirrhosis
OT  - hypoxia
OT  - oxidative stress
COIS- The authors declare no conflict of interest. The funders had no role in this 
      study's design; in the collection, analyses, or interpretation of data; in the 
      writing of the manuscript; or in the decision to publish the results.
EDAT- 2023/04/28 06:41
MHDA- 2023/04/28 06:42
PMCR- 2023/04/03
CRDT- 2023/04/28 01:20
PHST- 2023/03/05 00:00 [received]
PHST- 2023/03/27 00:00 [revised]
PHST- 2023/03/31 00:00 [accepted]
PHST- 2023/04/28 06:42 [medline]
PHST- 2023/04/28 06:41 [pubmed]
PHST- 2023/04/28 01:20 [entrez]
PHST- 2023/04/03 00:00 [pmc-release]
AID - antiox12040872 [pii]
AID - antioxidants-12-00872 [pii]
AID - 10.3390/antiox12040872 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2023 Apr 3;12(4):872. doi: 10.3390/antiox12040872.