Venetoclax Induces Cardiotoxicity through Modulation of Oxidative-Stress-Mediated Cardiac Inflammation and Apoptosis via NF-κB and BCL-2 Pathway

Cardiovascular damage induced by anticancer therapy has become the main health problem after tumor elimination. Venetoclax (VTX) is a promising novel agent that has been proven to have a high efficacy in multiple hematological diseases, especially acute myeloid leukemia (AML) and chronic lymphocytic...

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Bibliographic Details
Published in:	International journal of molecular sciences Vol. 23; no. 11; p. 6260
Main Authors:	AlAsmari, Abdullah F, Alghamdi, Adel, Ali, Nemat, Almeaikl, Muath A, Hakami, Hassan M, Alyousef, Meshal K, AlSwayyed, Mohammed, Alharbi, Metab, Alqahtani, Faleh, Alasmari, Fawaz, Alsaleh, Nasser
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 02-06-2022 MDPI
Subjects:	Acute myeloid leukemia Apoptosis Bcl-2 protein Cancer therapies Cardiotoxicity Chemotherapy Chronic lymphocytic leukemia Drug dosages Drug withdrawal Enzymes Gene expression Heart Hematological diseases Inflammation Leukemia Lymphoma Markers Mortality NF-κB protein Oxidative stress Proteins Toxicity Tumors venetoclax apoptosis cardiotoxicity venetoclax inflammation oxidative stress
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Summary:	Cardiovascular damage induced by anticancer therapy has become the main health problem after tumor elimination. Venetoclax (VTX) is a promising novel agent that has been proven to have a high efficacy in multiple hematological diseases, especially acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL). Considering its mechanism of action, the possibility that VTX may cause cardiotoxicity cannot be ruled out. Therefore, this study was designed to investigate the toxic effect of VTX on the heart. Male Sprague-Dawley rats were randomly divided into three groups: control, low-dose VTX (50 mg/kg via oral gavage), and high-dose VTX (100 mg/kg via oral gavage). After 21 days, blood and tissue samples were collected for histopathological, biochemical, gene, and protein analyses. We demonstrated that VTX treatment resulted in cardiac damages as evidenced by major changes in histopathology and markedly elevated cardiac enzymes and hypertrophic genes markers. Moreover, we observed a drastic increase in oxidative stress, as well as inflammatory and apoptotic markers, with a remarkable decline in the levels of . To the best of our knowledge, this study is the first to report the cardiotoxic effect of VTX. Further experiments and future studies are strongly needed to comprehensively understand the cardiotoxic effect of VTX.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms23116260