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. 2021 May 15:273:119261.
doi: 10.1016/j.lfs.2021.119261. Epub 2021 Feb 27.

Evaluation of the effect of heat shock protein 70 targeted drugs on cirrhotic cardiomyopathy in biliary cirrhotic rats

Zeinab Esmaeili  1 , Qamar Niaz  2 , Partow Mirzaee Saffari  1 , Ahmad-Reza Dehpour  3 , Seyed Mahdi Rezayat  4 , Farahnaz Jazaeri  5
Affiliations

Evaluation of the effect of heat shock protein 70 targeted drugs on cirrhotic cardiomyopathy in biliary cirrhotic rats

Zeinab Esmaeili et al. Life Sci. .

Abstract

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-α), 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-α, 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.

Keywords: Bile duct ligation; Chronotropic responses; Cirrhotic cardiomyopathy; Heat shock protein 70; Liver cirrhosis; Teprenone.

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