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

• Published in: Life sciences (1973) 2021-05, Vol.273, p.119261, Article 119261
• Main Authors: Esmaeili, Zeinab, Niaz, Qamar, Saffari, Partow Mirzaee, Dehpour, Ahmad-Reza, Rezayat, Seyed Mahdi, Jazaeri, Farahnaz
• Format: Article
• Language: English
• Subjects: Alanine; Alanine transaminase; Animals; Anti-Ulcer Agents - pharmacology; Apoptosis; Aspartate aminotransferase; Autophagy; BAX protein; Bcl-2 protein; Bcl-x protein; Bile; Bile duct ligation; Bile ducts; Biomarkers - metabolism; Brain natriuretic peptide; Brain tumors; Cardiomyopathies - drug therapy; Cardiomyopathies - etiology; Cardiomyopathies - metabolism; Cardiomyopathies - pathology; Cardiomyopathy; Chronotropic responses; Cirrhosis; Cirrhotic cardiomyopathy; Diterpenes - pharmacology; EKG; Electrocardiography; Gene Expression Regulation - drug effects; Heat shock protein 70; Heat shock proteins; HSP70 Heat-Shock Proteins - antagonists & inhibitors; Hsp70 protein; Interleukin 6; Liver; Liver cirrhosis; Liver Cirrhosis, Biliary - complications; Lymphocytes B; Lymphoma; Male; Monocyte chemoattractant protein 1; Monocytes; Phagocytosis; Polymerase chain reaction; Rats; Rats, Wistar; Real time; Rodents; Teprenone; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.119261

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. 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). 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. 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. [Display omitted]