Details

Autor(en) / Beteiligte

• Fu, Yao
• Hu, Nan
• Cao, Ming
• Li, Wen-Feng
• Yang, Xin-Rui
• Gao, Jin-Lai
• Zhao, Jing
• Jiang, Man
• Ma, Ming-Hui
• Sun, Zhi-Jie
• Dong, De-Li

Titel

Anthelmintic niclosamide attenuates pressure-overload induced heart failure in mice

Ist Teil von

• European journal of pharmacology, 2021-12, Vol.912, p.174614-174614, Article 174614

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• The heart is a high energy demand organ and enhancing mitochondrial function is proposed as the next-generation therapeutics for heart failure. Our previous study found that anthelmintic drug niclosamide enhanced mitochondrial respiration and increased adenosine triphosphate (ATP) production in cardiomyocytes, therefore, this study aimed to determine the effect of niclosamide on heart failure in mice and the potential molecular mechanisms. The heart failure model was induced by transverse aortic constriction (TAC) in mice. Oral administration of niclosamide improved TAC-induced cardiac hypertrophy, cardiac fibrosis, and cardiac dysfunction in mice. Oral administration of niclosamide reduced TAC-induced increase of serum IL-6 in heart failure mice. In vitro, niclosamide within 0.1 μM increased mitochondrial respiration and ATP production in mice heart tissues. At the concentrations more than 0.1 μM, niclosamide reduced the increased interleukin- 6 (IL-6) mRNA expression in lipopolysaccharide (LPS)-stimulated RAW264.7 and THP-1 derived macrophages. In cultured primary cardiomyocytes and cardiac fibroblasts, niclosamide (more than 0.1 μM) suppressed IL-6- and phenylephrine-induced cardiomyocyte hypertrophy, and inhibited collagen secretion from cardiac fibroblasts. In conclusion, niclosamide attenuates heart failure in mice and the underlying mechanisms include enhancing mitochondrial respiration of cardiomyocytes, inhibiting collagen secretion from cardiac fibroblasts, and reducing the elevated serum inflammatory mediator IL-6. The present study suggests that niclosamide might be therapeutic for heart failure.