Betaine Intervention as a Novel Approach to Preventing Doxorubicin-Induced Cardiotoxicity
The anthracycline anticancer drug doxorubicin (Dox) is widely prescribed for treating lung, ovary, breast, lymphoma, sarcoma, and pediatric cancer. Mechanistically, Dox intercalates the DNA and inhibits the topoisomerase II enzyme in fast-proliferating cancer. The clinical application of Dox is limi...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Advances in Redox Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667137923000243 |
| _version_ | 1827590996906475520 |
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| author | Aiswarya Jaiswal Pushkar Singh Rawat Sumeet Kumar Singh Jasvinder Singh Bhatti Amit Khurana Umashanker Navik |
| author_facet | Aiswarya Jaiswal Pushkar Singh Rawat Sumeet Kumar Singh Jasvinder Singh Bhatti Amit Khurana Umashanker Navik |
| author_sort | Aiswarya Jaiswal |
| collection | DOAJ |
| description | The anthracycline anticancer drug doxorubicin (Dox) is widely prescribed for treating lung, ovary, breast, lymphoma, sarcoma, and pediatric cancer. Mechanistically, Dox intercalates the DNA and inhibits the topoisomerase II enzyme in fast-proliferating cancer. The clinical application of Dox is limited due to its cardiotoxicity, including congestive heart failure, alterations in myocardial structure, arrhythmia, and left ventricular dysfunction. Dox causes cardiotoxicity via various mechanisms, including oxidative stress, mitochondrial dysfunctioning, deranged Ca2+ homeostasis, inflammation, fibrosis, downregulating AMPK, etc. Betaine is a zwitterion-based drug known as N, N, N trimethylglycine that regulates the methionine cycle and homocysteine (a risk factor for cardiovascular disease) detoxification through betaine-homocysteine methyltransferases. Betaine is nontoxic and has several beneficial effects in different disease models. Betaine treatment decreases the amyloid β generation, reduces obesity, improves steatosis and fibrosis, and activates AMP-activated protein kinase (AMPK). Further, betaine downregulates 8‑hydroxy-2-deoxyguanosine, malondialdehyde, and upregulates catalases, glutathione peroxidase, and superoxide dismutase activity. Therefore, we hypothesized that betaine might be a rational drug candidate to effectively combat Dox-associated oxidative stress, inflammation, and mitochondrial dysfunction. |
| first_indexed | 2024-03-09T01:25:33Z |
| format | Article |
| id | doaj.art-9fe916f805c1404f84d0c30653ae7c87 |
| institution | Directory Open Access Journal |
| issn | 2667-1379 |
| language | English |
| last_indexed | 2024-03-09T01:25:33Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Advances in Redox Research |
| spelling | doaj.art-9fe916f805c1404f84d0c30653ae7c872023-12-10T06:18:52ZengElsevierAdvances in Redox Research2667-13792023-12-019100084Betaine Intervention as a Novel Approach to Preventing Doxorubicin-Induced CardiotoxicityAiswarya Jaiswal0Pushkar Singh Rawat1Sumeet Kumar Singh2Jasvinder Singh Bhatti3Amit Khurana4Umashanker Navik5Department of Pharmacology, Central University Punjab, Bathinda, Punjab 151401, IndiaDepartment of Pharmacology, Central University Punjab, Bathinda, Punjab 151401, IndiaDepartment of Pharmacology, Central University Punjab, Bathinda, Punjab 151401, IndiaLaboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda 151401, Punjab, IndiaInstitute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH Aachen University Hospital, Pauwelsstr. 30, Aachen D-52074, GermanyDepartment of Pharmacology, Central University Punjab, Bathinda, Punjab 151401, India; Corresponding author.The anthracycline anticancer drug doxorubicin (Dox) is widely prescribed for treating lung, ovary, breast, lymphoma, sarcoma, and pediatric cancer. Mechanistically, Dox intercalates the DNA and inhibits the topoisomerase II enzyme in fast-proliferating cancer. The clinical application of Dox is limited due to its cardiotoxicity, including congestive heart failure, alterations in myocardial structure, arrhythmia, and left ventricular dysfunction. Dox causes cardiotoxicity via various mechanisms, including oxidative stress, mitochondrial dysfunctioning, deranged Ca2+ homeostasis, inflammation, fibrosis, downregulating AMPK, etc. Betaine is a zwitterion-based drug known as N, N, N trimethylglycine that regulates the methionine cycle and homocysteine (a risk factor for cardiovascular disease) detoxification through betaine-homocysteine methyltransferases. Betaine is nontoxic and has several beneficial effects in different disease models. Betaine treatment decreases the amyloid β generation, reduces obesity, improves steatosis and fibrosis, and activates AMP-activated protein kinase (AMPK). Further, betaine downregulates 8‑hydroxy-2-deoxyguanosine, malondialdehyde, and upregulates catalases, glutathione peroxidase, and superoxide dismutase activity. Therefore, we hypothesized that betaine might be a rational drug candidate to effectively combat Dox-associated oxidative stress, inflammation, and mitochondrial dysfunction.http://www.sciencedirect.com/science/article/pii/S2667137923000243DoxorubicinOxidative stressInflammationCardiotoxicityBetaineAnti-oxidant |
| spellingShingle | Aiswarya Jaiswal Pushkar Singh Rawat Sumeet Kumar Singh Jasvinder Singh Bhatti Amit Khurana Umashanker Navik Betaine Intervention as a Novel Approach to Preventing Doxorubicin-Induced Cardiotoxicity Advances in Redox Research Doxorubicin Oxidative stress Inflammation Cardiotoxicity Betaine Anti-oxidant |
| title | Betaine Intervention as a Novel Approach to Preventing Doxorubicin-Induced Cardiotoxicity |
| title_full | Betaine Intervention as a Novel Approach to Preventing Doxorubicin-Induced Cardiotoxicity |
| title_fullStr | Betaine Intervention as a Novel Approach to Preventing Doxorubicin-Induced Cardiotoxicity |
| title_full_unstemmed | Betaine Intervention as a Novel Approach to Preventing Doxorubicin-Induced Cardiotoxicity |
| title_short | Betaine Intervention as a Novel Approach to Preventing Doxorubicin-Induced Cardiotoxicity |
| title_sort | betaine intervention as a novel approach to preventing doxorubicin induced cardiotoxicity |
| topic | Doxorubicin Oxidative stress Inflammation Cardiotoxicity Betaine Anti-oxidant |
| url | http://www.sciencedirect.com/science/article/pii/S2667137923000243 |
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