PMID- 30529771
OWN - NLM
STAT- MEDLINE
DCOM- 20190418
LR  - 20190418
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 110
DP  - 2019 Feb
TI  - Tropisetron inhibits sepsis by repressing hyper-inflammation and regulating the 
      cardiac action potential in rat models.
PG  - 380-388
LID - S0753-3322(18)35470-2 [pii]
LID - 10.1016/j.biopha.2018.11.142 [doi]
AB  - OBJECTIVE: The objective of the present investigation was to explore the possible 
      effect of the 5-HT3 receptor antagonist tropisetron on the expression levels of 
      the inflammatory factors interleukin 6 (IL-6), creatine kinase isoenzyme (CK-MB), 
      soluble growth stimulating gene 2 protein (sST2) and immunoglobulin E (IgE), as 
      well as the cardiac action potential in septic rats. METHODS: The cecal ligation 
      and perforation (CLP) method was utilized to construct abdominal infarction in 
      rats. A total of 68 male adult Sprague Dawley rats were used, including 40 for 
      assessing survival and 28 for detecting the expression levels of IL-6 and IgE, 
      myocardial injury, cardiac dysfunction and the cardiac action potential. These 28 
      rats were divided into the sham (6 rats), sham + Tropisetron (6 rats), CLP (8 
      rats) and CLP + Tropisetron (8 rats) groups. Twenty-four hours after 
      establishment of the sepsis rat model, immunohistochemistry was used to analyze 
      5-HT3 receptor protein expression, and enzyme-linked immunosorbent assay (ELISA) 
      was employed to monitor the serum levels of IL-6, CKMB, sST2 and IgE. 
      Furthermore, the structure of the myocardium in various groups was examined by 
      H&E staining. RESULTS: The levels of IL-6, CK-MB, sST2 and IgE in the sepsis 
      group were significantly higher than those of the sham group (P <  0.01). 
      Furthermore, the heart rate in the sepsis group was lower than that of the sham 
      group (P <  0.01), and the time of atrial ventricular action potential in the 
      sepsis group was longer than that of the sham group (P <  0.05). In addition, 
      immunohistochemical analyses showed that the area, intensity and index of 5-HT3 
      receptor in the sepsis group were significantly lower than those of the sham 
      group (P <  0.01). Importantly, the 5-HT3 receptor antagonist Tropisetron 
      exhibited significant inhibitory effects IL-6, CK-MB, sST2 and IgE expression 
      levels, and inductive effects on atrial ventricular action potential in the 
      sepsis group. CONCLUSIONS: Sepsis leads to systemic inflammatory reaction, 
      resulting in myocardial injury, structural changes and immune imbalance. The 
      inhibitory effect of tropisetron on inflammation, and the regulatory inflammatory 
      disorder by the efferent vagus nerve may be one of the important mechanisms 
      leading to cardiac electrophysiological changes in sepsis.
CI  - Copyright (c) 2018. Published by Elsevier Masson SAS.
FAU - Liu, Zhengjiang
AU  - Liu Z
AD  - Department of Cardiology, the Six Affiliated Hospital of Guangzhou Medical 
      University/ Qingyuan People's Hospital, Qingyuan 511500, China. Electronic 
      address: 29542006j@sina.com.
FAU - Zeng, Zhiheng
AU  - Zeng Z
AD  - Department of Cardiology, the First Affiliated Hospital of Guangdong 
      Pharmaceutical University, Guangzhou 510080, China.
FAU - Wu, Changdong
AU  - Wu C
AD  - NO.1 Deppartment of ICU, the People's Hospital of Xinjiang Uygur Autonomous 
      Region, Urumqi 830000, China.
FAU - Liu, Hua
AU  - Liu H
AD  - Department of Cardiology, the Six Affiliated Hospital of Guangzhou Medical 
      University/ Qingyuan People's Hospital, Qingyuan 511500, China.
LA  - eng
PT  - Journal Article
DEP - 20181204
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Inflammation Mediators)
RN  - 0 (Serotonin 5-HT3 Receptor Antagonists)
RN  - 6I819NIK1W (Tropisetron)
SB  - IM
MH  - Action Potentials/*drug effects/physiology
MH  - Animals
MH  - Disease Models, Animal
MH  - Heart/*drug effects/physiology
MH  - Inflammation/drug therapy/metabolism
MH  - Inflammation Mediators/*antagonists & inhibitors/metabolism
MH  - Isolated Heart Preparation/methods
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sepsis/*drug therapy/metabolism
MH  - Serotonin 5-HT3 Receptor Antagonists/pharmacology/*therapeutic use
MH  - Tropisetron/pharmacology/*therapeutic use
OTO - NOTNLM
OT  - 5-HT3
OT  - Cardiac electrophysiology
OT  - IL-6
OT  - IgE
OT  - Sepsis
OT  - sST2
EDAT- 2018/12/12 06:00
MHDA- 2019/04/19 06:00
CRDT- 2018/12/12 06:00
PHST- 2018/08/07 00:00 [received]
PHST- 2018/11/22 00:00 [revised]
PHST- 2018/11/28 00:00 [accepted]
PHST- 2018/12/12 06:00 [pubmed]
PHST- 2019/04/19 06:00 [medline]
PHST- 2018/12/12 06:00 [entrez]
AID - S0753-3322(18)35470-2 [pii]
AID - 10.1016/j.biopha.2018.11.142 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2019 Feb;110:380-388. doi: 10.1016/j.biopha.2018.11.142. 
      Epub 2018 Dec 4.