PMID- 33652036
OWN - NLM
STAT- MEDLINE
DCOM- 20210407
LR  - 20210407
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 273
DP  - 2021 May 15
TI  - Evaluation of the effect of heat shock protein 70 targeted drugs on cirrhotic 
      cardiomyopathy in biliary cirrhotic rats.
PG  - 119261
LID - S0024-3205(21)00246-0 [pii]
LID - 10.1016/j.lfs.2021.119261 [doi]
AB  - AIMS: Liver cirrhosis leads to cirrhotic cardiomyopathy (CCM) and chronotropic 
      incompetence (CI). Heat shock protein 70 (Hsp70) regulates cellular apoptosis and 
      autophagy in stress. Teprenone modulates the Hsp70 and protects against cellular 
      injury. Thus, we aimed to evaluate the effect of teprenone on CI in biliary 
      cirrhotic rats. MAIN METHODS: Liver cirrhosis was induced in male Wistar rats 
      through bile duct ligation (BDL). The chronotropic responses and QT interval were 
      studied through electrocardiography (ECG) in sham, cirrhotic, and 
      cirrhotic/teprenone (100 mg/kg) pre-treated groups. Brain natriuretic peptide 
      (BNP), tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), and monocyte 
      chemo-attractant protein-1 (MCP-1), and alanine aminotransferase (ALT) and 
      aspartate aminotransferase (AST) levels were investigated in serum. The Hsp70, 
      B-cell lymphoma 2 (Bcl-2), and B-cell lymphoma 2-associated X protein (Bax) 
      expressions were quantified through real-time polymerase chain reaction 
      (Real-time PCR). KEY FINDINGS: The chronotropic responses were decreased 
      significantly in cirrhotic and cirrhotic/teprenone groups. The QT interval and 
      serum BNP, TNF-alpha, IL-6, ALT, AST, and MCP-1 levels were increased significantly 
      in the cirrhotic and decreased significantly, except BNP, in the 
      cirrhotic/teprenone group. The Hsp70 and Bax expressions increased significantly 
      in cirrhotic and decreased significantly in the cirrhotic/teprenone group while 
      the Bcl-2 decreased significantly in cirrhotic and increased significantly in the 
      cirrhotic/teprenone group. SIGNIFICANCE: Teprenone does not relieve the CI and 
      BNP changes in CCM while other indices are treated. Given that CCM is a 
      multifactorial disease and needs to target other genes and proteins concurrent 
      with Hsp70 to relieve CCM.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Esmaeili, Zeinab
AU  - Esmaeili Z
AD  - Department of Pharmacology, School of Medicine, Tehran University of Medical 
      Sciences, Tehran, Iran.
FAU - Niaz, Qamar
AU  - Niaz Q
AD  - Department of Pharmacology, School of Medicine, Tehran University of Medical 
      Sciences, Tehran, Iran; On leave from the Department of Pharmacology and 
      Toxicology, Faculty of Bio-Sciences, University of Veterinary and Animal 
      Sciences, Lahore, Punjab, Pakistan. Electronic address: qamar.niaz@uvas.edu.pk.
FAU - Saffari, Partow Mirzaee
AU  - Saffari PM
AD  - Department of Pharmacology, School of Medicine, Tehran University of Medical 
      Sciences, Tehran, Iran.
FAU - Dehpour, Ahmad-Reza
AU  - Dehpour AR
AD  - Department of Pharmacology, School of Medicine, Tehran University of Medical 
      Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University 
      of Medical Sciences, Tehran, Iran.
FAU - Rezayat, Seyed Mahdi
AU  - Rezayat SM
AD  - Department of Pharmacology, School of Medicine, Tehran University of Medical 
      Sciences, Tehran, Iran. Electronic address: rezayat@tums.ac.ir.
FAU - Jazaeri, Farahnaz
AU  - Jazaeri F
AD  - Department of Pharmacology, School of Medicine, Tehran University of Medical 
      Sciences, Tehran, Iran. Electronic address: f-jazaeri@sina.tums.ac.ir.
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
DEP - 20210227
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Anti-Ulcer Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Diterpenes)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - S8S8451A4O (geranylgeranylacetone)
SB  - IM
MH  - Animals
MH  - Anti-Ulcer Agents/*pharmacology
MH  - Biomarkers/*metabolism
MH  - Cardiomyopathies/*drug therapy/etiology/metabolism/pathology
MH  - Diterpenes/*pharmacology
MH  - Gene Expression Regulation/*drug effects
MH  - HSP70 Heat-Shock Proteins/*antagonists & inhibitors
MH  - Liver Cirrhosis, Biliary/*complications
MH  - Male
MH  - Rats
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Bile duct ligation
OT  - Chronotropic responses
OT  - Cirrhotic cardiomyopathy
OT  - Heat shock protein 70
OT  - Liver cirrhosis
OT  - Teprenone
EDAT- 2021/03/03 06:00
MHDA- 2021/04/10 06:00
CRDT- 2021/03/02 20:08
PHST- 2020/10/13 00:00 [received]
PHST- 2021/02/13 00:00 [revised]
PHST- 2021/02/16 00:00 [accepted]
PHST- 2021/03/03 06:00 [pubmed]
PHST- 2021/04/10 06:00 [medline]
PHST- 2021/03/02 20:08 [entrez]
AID - S0024-3205(21)00246-0 [pii]
AID - 10.1016/j.lfs.2021.119261 [doi]
PST - ppublish
SO  - Life Sci. 2021 May 15;273:119261. doi: 10.1016/j.lfs.2021.119261. Epub 2021 Feb 
      27.