{"title":"The potential treatment of N-acetylcysteine as an antioxidant in the radiation-induced heart disease.","authors":"Yan-Ling Li, Gang Wang, Bo-Wen Wang, Yong-Hong Li, Yong-Xia Ma, Yuan Huang, Wen-Ting Yan, Ping Xie","doi":"10.21037/cdt-24-19","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Radiation-induced heart disease (RIHD) is a serious complication of thoracic tumor radiotherapy that substantially affects the quality of life of cancer patients. Oxidative stress plays a pivotal role in the occurrence and progression of RIHD, which prompted our investigation of an innovative approach for treating RIHD using antioxidant therapy.</p><p><strong>Methods: </strong>We used 8-week-old male Sprague-Dawley (SD) rats as experimental animals and H9C2 cells as experimental cells. N-acetylcysteine (NAC) was used as an antioxidant to treat H9C2 cells after X-ray irradiation in this study. In the present study, the extent of cardiomyocyte damage caused by X-ray exposure was determined, alterations in oxidation/antioxidation levels were assessed, and changes in the expression of genes related to mitochondria were examined. The degree of myocardial tissue and cell injury was also determined. Dihydroethidium (DHE) staining, reactive oxygen species (ROS) assays, and glutathione (GSH) and manganese superoxide dismutase (Mn-SOD) assays were used to assess cell oxidation/antioxidation. Flow cytometry was used to determine the mitochondrial membrane potential and mitochondrial permeability transition pore (mPTP) opening. High-throughput transcriptome sequencing and bioinformatics analysis were used to elucidate the expression of mitochondria-related genes in myocardial tissue induced by X-ray exposure. Polymerase chain reaction (PCR) was used to verify the expression of differentially expressed genes.</p><p><strong>Results: </strong>X-ray irradiation damaged myocardial tissue and cells, resulting in an imbalance of oxidative and antioxidant substances and mitochondrial damage. NAC treatment increased cell counting kit-8 (CCK-8) levels (P=0.02) and decreased lactate dehydrogenase (LDH) release (P=0.02) in cardiomyocytes. It also reduced the level of ROS (P=0.002) and increased the levels of GSH (P=0.04) and Mn-SOD (P=0.01). The mitochondrial membrane potential was restored (P<0.001), and mPTP opening was inhibited (P<0.001). Transcriptome sequencing and subsequent validation analyses revealed a decrease in the expression of mitochondria-related genes in myocardial tissue induced by X-ray exposure, but antioxidant therapy did not reverse the related DNA damage.</p><p><strong>Conclusions: </strong>Antioxidants mitigated radiation-induced myocardial damage to a certain degree, but these agents did not reverse the associated DNA damage. These findings provide a new direction for future investigations by our research group, including exploring the treatment of RIHD-related DNA damage.</p>","PeriodicalId":9592,"journal":{"name":"Cardiovascular diagnosis and therapy","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384455/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular diagnosis and therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.21037/cdt-24-19","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/21 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Radiation-induced heart disease (RIHD) is a serious complication of thoracic tumor radiotherapy that substantially affects the quality of life of cancer patients. Oxidative stress plays a pivotal role in the occurrence and progression of RIHD, which prompted our investigation of an innovative approach for treating RIHD using antioxidant therapy.
Methods: We used 8-week-old male Sprague-Dawley (SD) rats as experimental animals and H9C2 cells as experimental cells. N-acetylcysteine (NAC) was used as an antioxidant to treat H9C2 cells after X-ray irradiation in this study. In the present study, the extent of cardiomyocyte damage caused by X-ray exposure was determined, alterations in oxidation/antioxidation levels were assessed, and changes in the expression of genes related to mitochondria were examined. The degree of myocardial tissue and cell injury was also determined. Dihydroethidium (DHE) staining, reactive oxygen species (ROS) assays, and glutathione (GSH) and manganese superoxide dismutase (Mn-SOD) assays were used to assess cell oxidation/antioxidation. Flow cytometry was used to determine the mitochondrial membrane potential and mitochondrial permeability transition pore (mPTP) opening. High-throughput transcriptome sequencing and bioinformatics analysis were used to elucidate the expression of mitochondria-related genes in myocardial tissue induced by X-ray exposure. Polymerase chain reaction (PCR) was used to verify the expression of differentially expressed genes.
Results: X-ray irradiation damaged myocardial tissue and cells, resulting in an imbalance of oxidative and antioxidant substances and mitochondrial damage. NAC treatment increased cell counting kit-8 (CCK-8) levels (P=0.02) and decreased lactate dehydrogenase (LDH) release (P=0.02) in cardiomyocytes. It also reduced the level of ROS (P=0.002) and increased the levels of GSH (P=0.04) and Mn-SOD (P=0.01). The mitochondrial membrane potential was restored (P<0.001), and mPTP opening was inhibited (P<0.001). Transcriptome sequencing and subsequent validation analyses revealed a decrease in the expression of mitochondria-related genes in myocardial tissue induced by X-ray exposure, but antioxidant therapy did not reverse the related DNA damage.
Conclusions: Antioxidants mitigated radiation-induced myocardial damage to a certain degree, but these agents did not reverse the associated DNA damage. These findings provide a new direction for future investigations by our research group, including exploring the treatment of RIHD-related DNA damage.
期刊介绍:
The journal ''Cardiovascular Diagnosis and Therapy'' (Print ISSN: 2223-3652; Online ISSN: 2223-3660) accepts basic and clinical science submissions related to Cardiovascular Medicine and Surgery. The mission of the journal is the rapid exchange of scientific information between clinicians and scientists worldwide. To reach this goal, the journal will focus on novel media, using a web-based, digital format in addition to traditional print-version. This includes on-line submission, review, publication, and distribution. The digital format will also allow submission of extensive supporting visual material, both images and video. The website www.thecdt.org will serve as the central hub and also allow posting of comments and on-line discussion. The web-site of the journal will be linked to a number of international web-sites (e.g. www.dxy.cn), which will significantly expand the distribution of its contents.