PMID- 24458046
OWN - NLM
STAT- MEDLINE
DCOM- 20140407
LR  - 20181203
IS  - 2163-0763 (Electronic)
IS  - 2163-0755 (Linking)
VI  - 76
IP  - 2
DP  - 2014 Feb
TI  - Resveratrol attenuates hypoxic injury in a primary hepatocyte model of 
      hemorrhagic shock and resuscitation.
PG  - 409-17
LID - 10.1097/TA.0000000000000096 [doi]
AB  - BACKGROUND: Oxidative stress following hemorrhagic shock and resuscitation (HSR) 
      is regulated, in part, by inflammatory and apoptotic mediators such as necrosis 
      factor kappaB (NF-kappaB) and p53. Sirtuin 1 (Sirt-1) is a metabolic intermediary that 
      regulates stress responses by suppressing NF-kappaB and p53 activity. Resveratrol is 
      a naturally occurring polyphenolic antioxidant and Sirt-1 agonist. The aim of 
      this study was to determine whether resveratrol protects hepatocytes following 
      HSR or hypoxia. METHODS: In vivo, HSR was achieved in male rats by arterial blood 
      withdrawal to 30 +/- 2 mm Hg for 1 hour before resuscitation with or without 
      resveratrol (Res, 30 mg/kg). Hepatic tissue was stained and scored for necrosis, 
      interleukin 6, and Sirt-1 expression. In vitro, primary rat hepatocytes were 
      subjected to 8 hours of hypoxia without or with Res (100 microM). Cells were analyzed 
      immediately or after 6 hours of normoxia, for survival and markers of injury 
      (lactate dehydrogenase assay, lipid peroxidation, and mitochondrial integrity). 
      Cell lysates were collected for cytochrome c analysis and immunoprecipitated 
      using antibodies against NF-kappaB (p65) or p53. RESULTS: In vivo, animals subject to 
      HSR exhibited increased expression of markers of hepatocyte damage compared with 
      those sham operated, concomitant with lower Sirt-1 expression. In vitro, hypoxia 
      followed by normoxia resulted in increased cell death, an effect that was blunted 
      by Res. Analysis of cell and mitochondrial function demonstrated that Res 
      inhibited the detrimental effects of hypoxia in isolated hepatocytes. CONCLUSION: 
      Resveratrol prevents cell death in HSR and exerts a protective effect on the 
      mitochondria in a hepatocyte model of hypoxic injury-reoxygenation possibly via 
      Sirt-1 modulation of p53 and NF-kappaB activity.
FAU - Powell, Rebecca D
AU  - Powell RD
AD  - From the FH "Sammy" Ross Trauma Center, Department of Surgery, Carolinas Medical 
      Center, Charlotte, North Carolina.
FAU - Swet, Jacob H
AU  - Swet JH
FAU - Kennedy, Kenneth L
AU  - Kennedy KL
FAU - Huynh, Toan T
AU  - Huynh TT
FAU - McKillop, Iain H
AU  - McKillop IH
FAU - Evans, Susan L
AU  - Evans SL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Trauma Acute Care Surg
JT  - The journal of trauma and acute care surgery
JID - 101570622
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Stilbenes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Death/drug effects
MH  - Cell Hypoxia/drug effects
MH  - Cell Survival
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Hepatocytes/*drug effects/metabolism
MH  - Immunohistochemistry
MH  - In Vitro Techniques
MH  - Interleukin-6/analysis/metabolism
MH  - Male
MH  - Mitochondria, Liver/metabolism
MH  - NF-kappa B/metabolism
MH  - Oxidative Stress/*drug effects
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reference Values
MH  - Resuscitation/*methods
MH  - Resveratrol
MH  - Shock, Hemorrhagic/mortality/physiopathology/*therapy
MH  - Sirtuin 1/drug effects/metabolism
MH  - Stilbenes/*pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2014/01/25 06:00
MHDA- 2014/04/08 06:00
CRDT- 2014/01/25 06:00
PHST- 2014/01/25 06:00 [entrez]
PHST- 2014/01/25 06:00 [pubmed]
PHST- 2014/04/08 06:00 [medline]
AID - 01586154-201402000-00022 [pii]
AID - 10.1097/TA.0000000000000096 [doi]
PST - ppublish
SO  - J Trauma Acute Care Surg. 2014 Feb;76(2):409-17. doi: 
      10.1097/TA.0000000000000096.