PMID- 34559743
OWN - NLM
STAT- MEDLINE
DCOM- 20220310
LR  - 20230824
IS  - 1540-0514 (Electronic)
IS  - 1073-2322 (Linking)
VI  - 57
IP  - 2
DP  - 2022 Feb 1
TI  - Sulforaphane-Dependent Up-Regulation of NRF2 Activity Alleviates Both Systemic 
      Inflammatory Response and Lung Injury After Hemorrhagic Shock/Resuscitation in 
      Mice.
PG  - 221-229
LID - 10.1097/SHK.0000000000001859 [doi]
AB  - Hemorrhagic shock/resuscitation (HS/R) is closely associated with overwhelming 
      oxidative stress and systemic inflammation. As an effective activator of the 
      nuclear factor-erythroid factor 2 related factor 2 (Nrf2) pathway, sulforaphane 
      (SFN) exerts antioxidant and anti-inflammatory effects. We explored SFN's effects 
      on alveolar macrophages (AMs), systemic inflammation, and pulmonary damage in an 
      isolated murine HS/R model. Male C57/BL6 wild type and transgenic antioxidant 
      response element (ARE)-luciferase (luc) mice (both n = 6 per group) were exposed 
      to either pressure-controlled HS/R (mean arterial pressure 35-45 mm Hg for 
      90 min) or sham procedure (surgery without HS/R) or were sacrificed without 
      intervention (control group). Fluid resuscitation was performed via the 
      reinfusion of withdrawn blood and 0.9% saline. Sulforaphane or 0.9% saline 
      (vehicle) was administrated intraperitoneally. Mice were sacrificed 6, 24, or 
      72 h after resuscitation. Bioluminescence imaging of ARE-luc mice was conducted 
      to measure pulmonary Nrf2 activity. Plasma was collected to determine systemic 
      cytokine levels. Alveolar macrophages were isolated before measuring cytokines in 
      the supernatant and performing immunofluorescence staining, as well as Western 
      blot for intracellular Nrf2. Histological damage was assessed via the acute lung 
      injury score and wet/dry ratio.Hemorrhagic shock/resuscitation was associated 
      with pulmonary Nrf2 activation. Sulforaphane enhanced pulmonary Nrf2 activity and 
      the Nrf2 activation of AM, while it decreased lung damage. Sulforaphane exerted 
      down-regulatory effects on AM-generated and systemic pro-inflammatory mediators, 
      while it did not have such effects on IL-10.In conclusion, SFN beneficially 
      enhances pulmonary Nrf2 activity and promotes Nrf2 accumulation in AMs' nuclei. 
      This may exert not only local protective effects but also systemic effects via 
      the down-regulation of pro-inflammatory cytokines. The administration of Nrf2 
      activator post-HS/R may represent an innovative treatment strategy.
CI  - Copyright (c) 2021 by the Shock Society.
FAU - Liang, Weiqiang
AU  - Liang W
AD  - Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital 
      RWTH Aachen, Aachen, Germany.
AD  - Department of Bone and Joint Surgery, The First Affiliated Hospital of Shandong 
      First Medical University, Jinan City, Shandong Province, PR China.
FAU - Greven, Johannes
AU  - Greven J
AD  - Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital 
      RWTH Aachen, Aachen, Germany.
FAU - Fragoulis, Athanassios
AU  - Fragoulis A
AD  - Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 
      Aachen, Germany.
FAU - Horst, Klemens
AU  - Horst K
AD  - Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital 
      RWTH Aachen, Aachen, Germany.
FAU - Blasius, Felix
AU  - Blasius F
AD  - Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital 
      RWTH Aachen, Aachen, Germany.
FAU - Wruck, Christoph
AU  - Wruck C
AD  - Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 
      Aachen, Germany.
FAU - Pufe, Thomas
AU  - Pufe T
AD  - Department of Anatomy and Cell Biology, RWTH Aachen University, Wendlingweg 2, 
      Aachen, Germany.
FAU - Kobbe, Philipp
AU  - Kobbe P
AD  - Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital 
      RWTH Aachen, Aachen, Germany.
FAU - Hildebrand, Frank
AU  - Hildebrand F
AD  - Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital 
      RWTH Aachen, Aachen, Germany.
FAU - Lichte, Philipp
AU  - Lichte P
AD  - Department of Orthopedics, Trauma and Reconstructive Surgery, University Hospital 
      RWTH Aachen, Aachen, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Isothiocyanates)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Sulfoxides)
RN  - GA49J4310U (sulforaphane)
SB  - IM
MH  - Acute Lung Injury/etiology/*physiopathology
MH  - Animals
MH  - Isothiocyanates/*pharmacology
MH  - Macrophages/*drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NF-E2-Related Factor 2/*physiology
MH  - Resuscitation
MH  - Shock, Hemorrhagic/complications
MH  - Sulfoxides/*pharmacology
MH  - Systemic Inflammatory Response Syndrome/etiology/*physiopathology
MH  - Up-Regulation/*drug effects
COIS- The other authors have no conflicts of interests in relation to this study.
EDAT- 2021/09/25 06:00
MHDA- 2022/03/11 06:00
CRDT- 2021/09/24 17:15
PHST- 2021/09/25 06:00 [pubmed]
PHST- 2022/03/11 06:00 [medline]
PHST- 2021/09/24 17:15 [entrez]
AID - 00024382-202202000-00009 [pii]
AID - 10.1097/SHK.0000000000001859 [doi]
PST - ppublish
SO  - Shock. 2022 Feb 1;57(2):221-229. doi: 10.1097/SHK.0000000000001859.