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Doxorubicin is an anthracycline widely used for the treatment of various cancers; however, the drug has a common deleterious side effect, namely a dose-dependent cardiotoxicity. Doxorubicin treatment increases the generation of reactive oxygen species, which leads to oxidative stress in the cardiac cells and ultimately DNA damage and cell death. The most common DNA lesion produced by oxidative stress is 7,8-dihydro-8-oxoguanine (8-oxoguanine), and the enzyme responsible for its repair is the 8-oxoguanine DNA glycosylase (OGG1), a base excision repair enzyme. Here, we show that the OGG1 deficiency has no major effect on cardiac function at baseline or with pressure overload; however, we found an exacerbation of cardiac dysfunction as well as a higher mortality in Ogg1 knockout mice treated with doxorubicin. Our transcriptomic analysis also showed a more extensive dysregulation of genes in the hearts of Ogg1 knockout mice with an enrichment of genes involved in inflammation. These results demonstrate that OGG1 attenuates doxorubicin-induced cardiotoxicity and thus plays a role in modulating drug-induced cardiomyopathy. Copyright © 2022 Chukwuemeka George Anene-Nzelu et al.


Chukwuemeka George Anene-Nzelu, Peter Yiqing Li, Tuan Danh Anh Luu, Shi Ling Ng, Zenia Tiang, Bangfen Pan, Wilson Lek Wen Tan, Matthew Ackers-Johnson, Ching Kit Chen, Yee Phong Lim, Rina Wang Miao Qin, Wee Woon Chua, Lim Xin Yi, Roger Sik-Yin Foo, Yusaku Nakabeppu. 8-Oxoguanine DNA Glycosylase (OGG1) Deficiency Exacerbates Doxorubicin-Induced Cardiac Dysfunction. Oxidative medicine and cellular longevity. 2022;2022:9180267

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PMID: 35391931

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