PMID- 27172157
OWN - NLM
STAT- MEDLINE
DCOM- 20180129
LR  - 20220311
IS  - 1540-0514 (Electronic)
IS  - 1073-2322 (Print)
IS  - 1073-2322 (Linking)
VI  - 46
IP  - 4
DP  - 2016 Oct
TI  - Role of Elevated Fibrinogen in Burn-Induced Mitochondrial Dysfunction: Protective 
      Effects of Glycyrrhizin.
PG  - 382-9
LID - 10.1097/SHK.0000000000000602 [doi]
AB  - INTRODUCTION: Skeletal muscle wasting and weakness with mitochondrial dysfunction 
      (MD) are major pathological problems in burn injury (BI) patients. Fibrinogen 
      levels elevated in plasma is an accepted risk factor for poor prognosis in many 
      human diseases, and is also designated one of damage-associated molecular pattern 
      (DAMPs) proteins. The roles of upregulated fibrinogen on muscle changes of 
      critical illness including BI are unknown. The hypothesis tested was that 
      BI-upregulated fibrinogen plays a pivotal role in the inflammatory responses and 
      MD in muscles, and that DAMPs inhibitor, glycyrrhizin mitigates the muscle 
      changes. METHODS: After third degree BI to mice, fibrinogen levels in the plasma 
      and at skeletal muscles were compared between BI and sham-burn (SB) mice. 
      Fibrinogen effects on inflammatory responses and mitochondrial membrane potential 
      (MMP) loss were analyzed in C2C12 myotubes. In addition to survival, the 
      anti-inflammatory and mitochondrial protective effects of glycyrrhizin were 
      tested using in vivo microscopy of skeletal muscles of BI and SB mice. RESULTS: 
      Fibrinogen in plasma and its extravasation to muscles significantly increased in 
      BI versus SB mice. Fibrinogen applied to myotubes evoked inflammatory responses 
      (increased MCP-1 and TNF-alpha; 32.6 and 3.9-fold, respectively) and reduced MMP; 
      these changes were ameliorated by glycyrrhizin treatment. In vivo MMP loss and 
      superoxide production in skeletal muscles of BI mice were significantly 
      attenuated by glycyrrhizin treatment, together with improvement of BI survival 
      rate. CONCLUSIONS: Inflammatory responses and MMP loss in myotubes induced by 
      fibrinogen were reversed by glycyrrhizin. Anti-inflammatory and mitochondrial 
      protective effect of glycyrrhizin in vivo leads to amelioration of muscle MD and 
      improvement of BI survival rate.
FAU - Ueki, Ryusuke
AU  - Ueki R
AD  - Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General 
      Hospital, Boston, Massachusetts; Shriners Hospital for Children, Boston, 
      Massachusetts; Harvard Medical School, Boston, Massachusetts; Department of 
      Anesthesiology and Pain Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, 
      Japan.
FAU - Liu, Li
AU  - Liu L
FAU - Kashiwagi, Shizuka
AU  - Kashiwagi S
FAU - Kaneki, Masao
AU  - Kaneki M
FAU - Khan, Mohammed A S
AU  - Khan MA
FAU - Hirose, Munetaka
AU  - Hirose M
FAU - Tompkins, Ronald G
AU  - Tompkins RG
FAU - Martyn, Jeevendra A J
AU  - Martyn JA
FAU - Yasuhara, Shingo
AU  - Yasuhara S
LA  - eng
GR  - P50 GM021700/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Reactive Oxygen Species)
RN  - 6FO62043WK (Glycyrrhizic Acid)
RN  - 9001-32-5 (Fibrinogen)
SB  - IM
MH  - Animals
MH  - Burns/*blood/*drug therapy/*metabolism
MH  - Cell Line
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fibrinogen/*metabolism/pharmacology
MH  - Glycyrrhizic Acid/*therapeutic use
MH  - Male
MH  - Membrane Potential, Mitochondrial/*drug effects
MH  - Mice
MH  - Muscle Fibers, Skeletal/drug effects/metabolism
MH  - Muscle, Skeletal/drug effects/metabolism
MH  - Reactive Oxygen Species/metabolism
PMC - PMC5026541
MID - NIHMS764518
EDAT- 2016/05/14 06:00
MHDA- 2018/01/30 06:00
PMCR- 2017/10/01
CRDT- 2016/05/13 06:00
PHST- 2016/05/13 06:00 [entrez]
PHST- 2016/05/14 06:00 [pubmed]
PHST- 2018/01/30 06:00 [medline]
PHST- 2017/10/01 00:00 [pmc-release]
AID - 10.1097/SHK.0000000000000602 [doi]
PST - ppublish
SO  - Shock. 2016 Oct;46(4):382-9. doi: 10.1097/SHK.0000000000000602.