Bioinformatics and experimental studies jointly reveal that Sacubitril Valsartan improves myocardial oxidative stress and inflammation by regulating the MAPK signaling pathway to treat chemotherapy related cardiotoxicity.

Abstract

BACKGROUND:

CRC is a common but serious complication or sequela of tumor treatment, and new coping strategies are urgently needed. SV is a classic clinical cardiovascular protective drug, which has been widely used in the treatment of heart failure, hypertension and other diseases. It has good therapeutic effect in other cardiovascular diseases such as diabetes cardiomyopathy, ischemic cardiomyopathy and vascular disease, but it has not been proved by research that SV can prevent and treat CRC.

METHOD:

In this study, DOX was used to induce a rat CRC model and evaluate the therapeutic effect of SV on it. Subsequently, R software was applied to analyze the control group, SV group, and DOX group in databases GSE207283 and GSE22369, and to screen for common differentially expressed genes. Use the DAVID website for enrichment analysis and visualization. Use STRING website to analyze and visualize protein interaction networks of key genes. Finally, experimental verification was conducted on key genes.

RESULT:

Our research results show that SV has a protective effect on DOX induced myocardial injury by alleviating Weight loss, increasing Ejection fraction, and reducing the level of biomarkers of myocardial injury. Meanwhile, SV can effectively alleviate the above abnormalities. Bioinformatics and KEGG pathway analysis showed significant enrichment of metabolic and MAPK signaling pathways, suggesting that they may be the main regulatory pathway for SV treatment of CRC. Subsequent studies have also confirmed that SV can inhibit DOX induced myocardial injury through the MAPK signaling pathway, and alleviate DOX induced oxidative stress and inflammatory states.

CONCLUSION:

Our research indicates that SV is a potential drug for treating CRC and preliminarily elucidates its molecular mechanism of regulating the MAPK pathway to improve oxidative stress and inflammation.

• Authors: Hongwei Shi, Hao Lu, Yanlei Zheng, Peng Pu, Lai Wei, Desheng Hu, Heng Tang, Linlin Wang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 690 Pg. 149244 (Jan 01 2024) ISSN: 1090-2104 [Electronic] United States
• PMID: 38029488 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier Inc. All rights reserved.

Chemical References

• sacubitril
• Doxorubicin
• Valsartan

Topics

• Rats
• Animals
• Cardiotoxicity (drug therapy, etiology, prevention & control)
• Doxorubicin (pharmacology)
• Apoptosis
• Oxidative Stress
• Signal Transduction
• Heart Injuries (metabolism)
• Valsartan (therapeutic use, metabolism, pharmacology)
• Cardiomyopathies (pathology)
• Inflammation (pathology)
• Computational Biology
• Myocytes, Cardiac (metabolism)