Evaluation of statins as a new therapy to alleviate chronotropic dysfunction in cirrhotic rats.
Animals
Male
Rats
Anti-Inflammatory Agents
/ therapeutic use
Antioxidants
/ metabolism
Atorvastatin
/ metabolism
Cholesterol
/ metabolism
Fibrosis
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ therapeutic use
Ligation
Liver
/ metabolism
Liver Cirrhosis
/ pathology
Malondialdehyde
/ metabolism
Natriuretic Peptides
/ metabolism
NF-E2-Related Factor 2
/ metabolism
Nitric Oxide Synthase Type III
/ metabolism
Rats, Wistar
rhoA GTP-Binding Protein
/ metabolism
Tumor Necrosis Factor-alpha
/ metabolism
Atorvastatin
Bile duct ligation (BDL)
Chronotropic responses
Cirrhotic cardiomyopathy (CCM)
Endothelial nitric oxide synthase (eNOS)
Ras homolog family member A (RhoA)
Journal
Life sciences
ISSN: 1879-0631
Titre abrégé: Life Sci
Pays: Netherlands
ID NLM: 0375521
Informations de publication
Date de publication:
01 Nov 2022
01 Nov 2022
Historique:
received:
28
04
2022
revised:
06
09
2022
accepted:
12
09
2022
pubmed:
24
9
2022
medline:
7
10
2022
entrez:
23
9
2022
Statut:
ppublish
Résumé
Liver cirrhosis defines by regenerative nodules and fibrotic septa, causing a complication called cirrhotic cardiomyopathy (CCM) with chronotropic hypo-responsiveness. In addition to lowering cholesterol levels, statins yield antioxidant and anti-inflammatory effects. In liver diseases animal models, statins have been shown to decrease hepatic inflammation, fibrogenesis, and portal pressure (PP). Therefore, we evaluated the atorvastatin effect on the heart in cirrhotic rats. Bile duct ligation (BDL) or sham operation performed on male Wistar rats and grouped as cirrhotic; BDL/Saline, BDL/Ator-7d(days) (Atorvastatin 15 mg/kg/day), and BDL/Ator-14d groups, or control; Sham/Saline, Sham/Ator-7d, and Sham/Ator-14d groups. Corrected QT interval (QTc interval), chronotropic responses, serum brain natriuretic peptides (BNP), heart tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), and malondialdehyde (MDA) levels were studied along with atrial Ras homolog family member A (RhoA) and endothelial nitric oxide synthase (eNOS) gene expression. The chronotropic responses decreased in BDL/Saline and increased in BDL/Ator-7d group. The QTc interval, BNP, TNF-α, and MDA levels increased in BDL/Saline and decreased in BDL/Ator-14d group. The Nrf2 level did not change in BDL/Saline and increased in BDL/Ator-14d group. The liver inflammation and fibrosis increased in BDL/Saline and did not affect BDL/Ator-7d and BDL/Ator-14d groups. The RhoA expression was down-regulated in BDL/Saline, BDL/Ator-7d, and BDL/Ator-14d groups. The eNOS expression did not change in BDL/Saline and down-regulated in BDL/Ator-14d group. Atorvastatin alleviates the chronotropic hypo-responsiveness and down-regulates the atrial RhoA and eNOS gene expression along with anti-inflammatory, antioxidant, and anti-stress effects in CCM.
Identifiants
pubmed: 36150464
pii: S0024-3205(22)00666-X
doi: 10.1016/j.lfs.2022.120966
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Antioxidants
0
Atorvastatin
A0JWA85V8F
Cholesterol
97C5T2UQ7J
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Malondialdehyde
4Y8F71G49Q
Natriuretic Peptides
0
NF-E2-Related Factor 2
0
Nitric Oxide Synthase Type III
EC 1.14.13.39
rhoA GTP-Binding Protein
EC 3.6.5.2
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
120966Informations de copyright
Copyright © 2022. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Conflict of interest statement The authors declare no conflicts of interest related to this work or its publication.