Zingerone Attenuates Carfilzomib-Induced Cardiotoxicity in Rats through Oxidative Stress and Inflammatory Cytokine Network

Carfilzomib (CFZ) is an anticancer medication acting as a selective proteasome inhibitor. However, it can cause cardiovascular problems, increasing mortality and morbidity. This study aimed to investigate whether zingerone (ZRN) could help reduce carfilzomib-induced cardiotoxicity in Wistar albino r...

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Bibliographic Details
Published in:	International journal of molecular sciences Vol. 23; no. 24; p. 15617
Main Authors:	Alam, Mohammad Firoz, Hijri, Sami I, Alshahrani, Saeed, Alqahtani, Saad S, Jali, Abdulmajeed M, Ahmed, Rayan A, Adawi, Mansour M, Algassmi, Sameeh M, Shaheen, Emad Sayed, Moni, Sivakumar S, Anwer, Tarique
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 09-12-2022 MDPI
Subjects:	Animals Antioxidants Antioxidants - metabolism Antioxidants - pharmacology Apoptosis Cancer Cardiotoxicity Cardiotoxicity - drug therapy Cardiotoxicity - etiology Cardiotoxicity - prevention & control cardiotoxicity histopathology Cardiovascular disease Cardiovascular diseases carfilzomib Caspase-3 Catalase Creatinine Cytokines Cytokines - pharmacology Drug dosages Enzymes Gene expression Glutathione - metabolism Heart attacks Heart failure Hematology IL-1β Inflammation Interleukin 6 Ischemia Kinases Lipid peroxidation Lipids Morbidity Multiple myeloma Oxidative Stress Proteasome inhibitors Proteasomes Pulmonary hypertension Rats Rats, Wistar Superoxide dismutase Tumor necrosis factor-α Zingerone apoptosis cytokines zingerone cardiotoxicity histopathology oxidative stress carfilzomib
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Summary:	Carfilzomib (CFZ) is an anticancer medication acting as a selective proteasome inhibitor. However, it can cause cardiovascular problems, increasing mortality and morbidity. This study aimed to investigate whether zingerone (ZRN) could help reduce carfilzomib-induced cardiotoxicity in Wistar albino rats. Rats were divided into five groups of six animals each. The first group received normal saline as a control (NC); the second group received multiple doses (six) of CFZ (4 mg/kg) intraperitoneally (IP); the third and fourth groups received zingerone (50 mg/kg and 100 mg/kg oral) along with six doses of CFZ for 16 days; and the fifth group received only 100 mg/kg zingerone orally. Hematological, biochemical, oxidative stress, and histopathological studies confirmed the findings of CFZ-induced cardiotoxicity. We found that ZRN significantly attenuated the effects of CFZ on oxidative stress by enhancing the antioxidant properties of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Additionally, ZRN reduces inflammatory cytokines and apoptotic markers, such as IL-1β, IL-6, TNFα, and caspase-3. Overall, zingerone prevents carfilzomib-induced cardiotoxicity in rats, as evidenced by histopathological studies.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms232415617