Tirzepatide protects against doxorubicin-induced cardiotoxicity by inhibiting oxidative stress and inflammation via PI3K/Akt signaling.
Peptides
; 178: 171245, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38801993
ABSTRACT
BACKGROUND:
Doxorubicin (DOX) is a highly effective and widely used cytotoxic agent with application for various malignancies, but it's clinically limited due to its cardiotoxicity Oxidative stress and inflammation were reported to take part in DOX-induced cardiotoxicity. Tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist has been approved to treat type 2 diabetes. However, its role in DOX-induced cardiotoxicity and the underlying mechanisms has not been explored.METHODS:
The cardioprotective properties of Tirzepatide against DOX-induced cardiotoxicity are examined in this work both in vivo and in vitro. For four weeks, an intraperitoneal injection of 4â¯mg/kg DOX was used to cause cardiotoxicity in C57BL/6 mice. To ascertain the cardioprotective function and underlying mechanisms of Tirzepatide against DOX-induced cardiotoxicity, mice and H9c2 cells were treated with and without Tirzepatide.RESULTS:
Tirzepatide treatment significantly inhibited DOX-induced oxidative stress, inflammation and cardiac injury. Mechanistically, PI3K/Akt signaling pathway contributes to the protective effect of Tirzepatide against DOX-induced cardiotoxicity and inhibited PI3K/Akt signaling pathway with LY294002 almost blocked its therapeutic effect.CONCLUSIONS:
Collectively, Tirzepatide could alleviate DOX-induced oxidative stress, inflammation and cardiac injury via activating PI3K/Akt signaling pathway and Tirzepatide may be a novel therapeutic target for DOX-induced cardiotoxicity.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Doxorubicin
/
Oxidative Stress
/
Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt
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Cardiotoxicity
/
Inflammation
Limits:
Animals
Language:
En
Journal:
Peptides
Year:
2024
Document type:
Article