Activation of the MET receptor attenuates doxorubicin-induced cardiotoxicity in vivo and in vitro.

ABSTRACT:

Background and purpose

Doxorubicin anti-cancer therapy is associated with cardiotoxicity, resulting from DNA damage response (DDR). Hepatocyte growth factor (HGF) protects cardiomyocytes from injury, but its effective use is compromised by low biodistribution. In this study, we have investigated whether the activation of the HGF receptor-encoded by the Met gene-by an agonist monoclonal antibody (mAb) could protect against doxorubicin-induced cardiotoxicity.

Experimental approach

The mAb (5 mg·kg^-1 ) was injected in vivo into C57BL/6J mice, before doxorubicin (three doses of 7 mg·kg^-1 ). Cardiac functions were evaluated through MRI after treatment termination. Heart histological staining and mRNA levels of genes associated with heart failure (Acta1 and N

SUBMITTER: Gallo S 

PROVIDER: S-EPMC7280013 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature