PMID- 28144715
OWN - NLM
STAT- MEDLINE
DCOM- 20190521
LR  - 20190521
IS  - 1615-6692 (Electronic)
IS  - 0340-9937 (Linking)
VI  - 43
IP  - 2
DP  - 2018 Mar
TI  - Cardioprotective effects of irbesartan in polymicrobial sepsis : The role of the 
      p38MAPK/NF-kappaB signaling pathway.
PG  - 140-145
LID - 10.1007/s00059-017-4537-6 [doi]
AB  - BACKGROUND: Sepsis is a systemic inflammatory response usually correlated with 
      multi-organ failure. Myocardial dysfunction is one of the adverse outcomes in 
      septic patients and results in high mortality rates. The aim of this study was to 
      investigate the impact of irbesartan in attenuation of cardiac depression during 
      polymicrobial sepsis via decreased activation of the phospho-p38MAPK/nuclear 
      factor (NF)-kappaB signaling pathway. MATERIALS AND METHODS: A model of polymicrobial 
      sepsis induced via cecal ligation and puncture (CLP) with 8- to 12-week-old 
      albino mice was used. Mice were treated with i.p. irbesartan (3 mg/kg) 1 h before 
      CLP. Using a micro-tipped transducer catheter, the following hemodynamic 
      parameters were evaluated after CLP: heart rate, ejection fraction, left 
      ventricular (LV) end-diastolic pressure, LV systolic pressure, and cardiac 
      output. Plasma levels of proinflammatory cytokines, including tumor necrosis 
      factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, monocyte chemoattractant 
      protein-1 (MCP-1), and cardiac troponin I (cTn-I), were measured via ELISA 
      analysis. The degree of p38MAPK and NF-kappaB phosphorylation was assessed via 
      Western blotting. RESULTS: Mice treated with irbesartan displayed improvement in 
      LV function (ejection fraction: 42.4 +/- 1.1% vs. 27.8 +/- 3% in CLP mice). The 
      attenuation of cardiac depression in irbesartan-treated mice was associated with 
      lower levels of MCP-1 in plasma and a reduction in the levels of TNF-alpha, 
      IL-1beta, and IL-6. Furthermore, irbesartan-treated mice displayed lower 
      expression levels of p38-MAPK and NF-kappaB phosphorylation. CONCLUSION: Irbesartan 
      can attenuate cardiac dysfunction during polymicrobial sepsis possibly via 
      a reduction of proinflammatory cytokines through decreased activation of the 
      p38MAPK/NF-kappaB pathways.
FAU - Yousif, N G
AU  - Yousif NG
AD  - Department of Medicine, Muthanna Medical College, Samawah, Iraq. 
      yousif_ghaly@yahoo.com.
AD  - Anschutz | Medical School, University of Colorado, Denver, USA. 
      yousif_ghaly@yahoo.com.
FAU - Hadi, N R
AU  - Hadi NR
AD  - Department of Pharmacology and Therapeutics, Kufa Medical College, University 
      Kufa, Kufa, Iraq.
FAU - Al-Amran, F
AU  - Al-Amran F
AD  - Department of Thoracic Surgery, Kufa Medical College, University Kufa, Kufa, 
      Iraq.
FAU - Zigam, Q A
AU  - Zigam QA
AD  - Department of Pharmacology and Therapeutics, Kufa Medical College, University 
      Kufa, Kufa, Iraq.
LA  - eng
PT  - Journal Article
TT  - Kardioprotektive Wirkungen von Irbesartan bei polymikrobieller Sepsis : Bedeutung 
      des p38MAPK/NF-kappaB-Signalwegs.
DEP - 20170131
PL  - Germany
TA  - Herz
JT  - Herz
JID - 7801231
RN  - 0 (Cardiotonic Agents)
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - J0E2756Z7N (Irbesartan)
SB  - IM
MH  - Animals
MH  - Cardiotonic Agents/*pharmacology
MH  - Coinfection/blood/*drug therapy
MH  - Cytokines/blood
MH  - Disease Models, Animal
MH  - Enzyme Activation/drug effects
MH  - Hemodynamics/drug effects
MH  - Injections, Intraperitoneal
MH  - Irbesartan/*pharmacology
MH  - Mice
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Premedication
MH  - Sepsis/blood/*drug therapy
MH  - Signal Transduction/*drug effects
MH  - p38 Mitogen-Activated Protein Kinases/*antagonists & inhibitors
OTO - NOTNLM
OT  - Acute-phase reaction
OT  - Anti-hypertensive agents
OT  - Cytokines
OT  - Hemodynamics
OT  - Septicemia
EDAT- 2017/02/02 06:00
MHDA- 2019/05/22 06:00
CRDT- 2017/02/02 06:00
PHST- 2016/10/11 00:00 [received]
PHST- 2017/01/08 00:00 [accepted]
PHST- 2016/12/31 00:00 [revised]
PHST- 2017/02/02 06:00 [pubmed]
PHST- 2019/05/22 06:00 [medline]
PHST- 2017/02/02 06:00 [entrez]
AID - 10.1007/s00059-017-4537-6 [pii]
AID - 10.1007/s00059-017-4537-6 [doi]
PST - ppublish
SO  - Herz. 2018 Mar;43(2):140-145. doi: 10.1007/s00059-017-4537-6. Epub 2017 Jan 31.