PMID- 32871182
OWN - NLM
STAT- MEDLINE
DCOM- 20201123
LR  - 20201123
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 261
DP  - 2020 Nov 15
TI  - Hydrocortisone mitigates ICU-AW by fine-tuning of muscle atrophic and 
      hypertrophic signaling pathways in a sepsis model with limb immobilization.
PG  - 118366
LID - S0024-3205(20)31119-X [pii]
LID - 10.1016/j.lfs.2020.118366 [doi]
AB  - AIMS: Intensive care unit-acquired weakness (ICU-AW) is a complex spectrum of 
      disability that delays recovery of critically ill-immobilized patients with 
      sepsis. Much discrepancy remain on the use of corticosteroids and their impact on 
      muscle regeneration in critical illness management. Therefore, the aim of this 
      study is to investigate whether hydrocortisone (HCT) modulates muscle mass 
      turnover in ICU-AW induced by sepsis with limb immobilization (SI). MAIN METHODS: 
      Sepsis by cecal ligation puncture (CLP) with forelimb-immobilization were 
      performed in rats. The study consisted of four groups: Sham (left 
      forelimb-immobilization), Sham HCT (left forelimb-immobilization + HCT), SI 
      (CLP + left forelimb-immobilization) and SI HCT (CLP + left 
      forelimb-immobilization + HCT). Motor force, blood and muscle sampling were 
      assessed. KEY FINDINGS: HCT prevented body weight loss associated with SI and 
      attenuated systemic and muscular inflammation. Besides, myosin was restituted in 
      SI HCT group in conjunction to muscle mass and strength restoration. 
      Pro-hypertrophic calcineurin (PP2B-Abeta) and nuclear factor of activated T-cells C3 
      (NFATc3) but not protein kinase B (Akt) were re-activated by HCT. Finally, 
      pro-atrophic extracellular signal-regulated kinases (ERK1/2) and p38 
      mitogen-activated protein kinases (p38) but not nuclear factor 
      kappa-light-chain-enhancer of activated B cells (NF-kB) were inhibited in SI HCT 
      group. SIGNIFICANCE: This study unravels new molecular events thought to control 
      muscle protein synthesis in ICU-AW induced by sepsis and limb immobilization. HCT 
      has a potential to fine-tune muscle-signaling pathways and to reduce the negative 
      outcomes of ICU-AW.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Habr, Bassem
AU  - Habr B
AD  - Laboratoire de Recherche en Physiologie et Physiopathologie, Pole Technologie 
      Sante, Faculte de Medecine, Universite Saint Joseph, Beirut, Lebanon; Faculte de 
      Medecine, Universite Saint Joseph, Beirut, Lebanon.
FAU - Saliba, Youakim
AU  - Saliba Y
AD  - Laboratoire de Recherche en Physiologie et Physiopathologie, Pole Technologie 
      Sante, Faculte de Medecine, Universite Saint Joseph, Beirut, Lebanon.
FAU - Hajal, Joelle
AU  - Hajal J
AD  - Laboratoire de Recherche en Physiologie et Physiopathologie, Pole Technologie 
      Sante, Faculte de Medecine, Universite Saint Joseph, Beirut, Lebanon.
FAU - Smayra, Viviane
AU  - Smayra V
AD  - Faculte de Medecine, Universite Saint Joseph, Beirut, Lebanon.
FAU - Riachy, Moussa
AU  - Riachy M
AD  - Faculte de Medecine, Universite Saint Joseph, Beirut, Lebanon.
FAU - Fares, Nassim
AU  - Fares N
AD  - Laboratoire de Recherche en Physiologie et Physiopathologie, Pole Technologie 
      Sante, Faculte de Medecine, Universite Saint Joseph, Beirut, Lebanon. Electronic 
      address: nassim.fares@usj.edu.lb.
LA  - eng
PT  - Journal Article
DEP - 20200829
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Inflammation Mediators)
RN  - 0 (NFATC Transcription Factors)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.4.1 (Myosins)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Animals
MH  - Body Weight
MH  - Disease Models, Animal
MH  - Extremities/*pathology
MH  - Hydrocortisone/pharmacology/*therapeutic use
MH  - Hypertrophy
MH  - *Immobilization
MH  - Inflammation Mediators/blood
MH  - *Intensive Care Units
MH  - Male
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Models, Biological
MH  - Muscle Weakness/blood/complications/*drug therapy
MH  - Muscular Atrophy/blood/complications/*drug therapy
MH  - Myosins/metabolism
MH  - NFATC Transcription Factors/metabolism
MH  - Organ Size/drug effects
MH  - Rats, Wistar
MH  - Sepsis/blood/*complications
MH  - *Signal Transduction
OTO - NOTNLM
OT  - Glucocorticoid
OT  - Hydrocortisone
OT  - ICU-acquired weakness
OT  - Immobilization
OT  - Sepsis
EDAT- 2020/09/02 06:00
MHDA- 2020/11/24 06:00
CRDT- 2020/09/02 06:00
PHST- 2020/06/11 00:00 [received]
PHST- 2020/08/14 00:00 [revised]
PHST- 2020/08/27 00:00 [accepted]
PHST- 2020/09/02 06:00 [pubmed]
PHST- 2020/11/24 06:00 [medline]
PHST- 2020/09/02 06:00 [entrez]
AID - S0024-3205(20)31119-X [pii]
AID - 10.1016/j.lfs.2020.118366 [doi]
PST - ppublish
SO  - Life Sci. 2020 Nov 15;261:118366. doi: 10.1016/j.lfs.2020.118366. Epub 2020 Aug 
      29.