{"title":"缺血再灌注大鼠心脏预处理和后适应对正常心脏的持续保护作用由于毒性，PM2.5暴露的心脏无效","authors":"Bhavana Sivakumar, Gino A. Kurian","doi":"10.1002/jbt.70471","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>The present study addresses the toxicological impact of Particulate matter (PM<sub>2.5</sub>) exposure on the pharmacological efficacy of ischemia preconditioning (IPC) and postconditioning (POC) against ischemia-reperfusion (IR) injury. The primary motivation for this study is the gap in knowledge regarding the effectiveness of IPC and POC in PM<sub>2.5</sub> modified hearts. With the increasing prevalence of cardiac procedures involving IR and PM<sub>2.5</sub> toxicity, there is a growing need to understand their interaction. Female Wistar rats were subjected to PM<sub>2.5</sub> exposure for 3 h daily over a period of 21 days. Subsequently, their hearts were excised and mounted on a Langendorff perfusion apparatus. Three cycles of IPC and POC were applied, followed by the IR protocol. In contrast to hearts under normal conditions, neither IPC nor POC could reduce cardiac injury (infarct size, apoptosis, and inflammation) or enhance cardiac function in PM<sub>2.5</sub>-exposed hearts subjected to IR. The underlying reason for this ineffectiveness was identified as the inability to improve mitochondrial bioenergetic function and the expression of the declined master regulator gene Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α). Additionally, the compromised mitochondrial quality control genes resulting from PM<sub>2.5</sub> exposure could not be restored to their normal levels by these conventional strategies. Furthermore, the crucial pro-survival signaling pathways like phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) could not be reactivated by these strategies in PM<sub>2.5</sub>-exposed hearts undergoing IR, consequently preventing the restoration of cardioprotection. From the above results, we deduce that the therapeutic benefits of mechanical conditioning techniques such as IPC and POC were compromised in hearts exposed to PM<sub>2.5</sub>, primarily attributed to PM<sub>2.5</sub> induced mitochondrial dysfunction.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pre-Conditioning and Post-Conditioning of Ischemia Reperfused Rat Hearts: Sustained Protection in Normal Hearts; Ineffective in PM2.5 Exposed Hearts Due to Toxicity\",\"authors\":\"Bhavana Sivakumar, Gino A. Kurian\",\"doi\":\"10.1002/jbt.70471\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>The present study addresses the toxicological impact of Particulate matter (PM<sub>2.5</sub>) exposure on the pharmacological efficacy of ischemia preconditioning (IPC) and postconditioning (POC) against ischemia-reperfusion (IR) injury. The primary motivation for this study is the gap in knowledge regarding the effectiveness of IPC and POC in PM<sub>2.5</sub> modified hearts. With the increasing prevalence of cardiac procedures involving IR and PM<sub>2.5</sub> toxicity, there is a growing need to understand their interaction. Female Wistar rats were subjected to PM<sub>2.5</sub> exposure for 3 h daily over a period of 21 days. Subsequently, their hearts were excised and mounted on a Langendorff perfusion apparatus. Three cycles of IPC and POC were applied, followed by the IR protocol. In contrast to hearts under normal conditions, neither IPC nor POC could reduce cardiac injury (infarct size, apoptosis, and inflammation) or enhance cardiac function in PM<sub>2.5</sub>-exposed hearts subjected to IR. The underlying reason for this ineffectiveness was identified as the inability to improve mitochondrial bioenergetic function and the expression of the declined master regulator gene Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α). Additionally, the compromised mitochondrial quality control genes resulting from PM<sub>2.5</sub> exposure could not be restored to their normal levels by these conventional strategies. Furthermore, the crucial pro-survival signaling pathways like phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) could not be reactivated by these strategies in PM<sub>2.5</sub>-exposed hearts undergoing IR, consequently preventing the restoration of cardioprotection. From the above results, we deduce that the therapeutic benefits of mechanical conditioning techniques such as IPC and POC were compromised in hearts exposed to PM<sub>2.5</sub>, primarily attributed to PM<sub>2.5</sub> induced mitochondrial dysfunction.</p></div>\",\"PeriodicalId\":15151,\"journal\":{\"name\":\"Journal of Biochemical and Molecular Toxicology\",\"volume\":\"39 9\",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biochemical and Molecular Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70471\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70471","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Pre-Conditioning and Post-Conditioning of Ischemia Reperfused Rat Hearts: Sustained Protection in Normal Hearts; Ineffective in PM2.5 Exposed Hearts Due to Toxicity
The present study addresses the toxicological impact of Particulate matter (PM2.5) exposure on the pharmacological efficacy of ischemia preconditioning (IPC) and postconditioning (POC) against ischemia-reperfusion (IR) injury. The primary motivation for this study is the gap in knowledge regarding the effectiveness of IPC and POC in PM2.5 modified hearts. With the increasing prevalence of cardiac procedures involving IR and PM2.5 toxicity, there is a growing need to understand their interaction. Female Wistar rats were subjected to PM2.5 exposure for 3 h daily over a period of 21 days. Subsequently, their hearts were excised and mounted on a Langendorff perfusion apparatus. Three cycles of IPC and POC were applied, followed by the IR protocol. In contrast to hearts under normal conditions, neither IPC nor POC could reduce cardiac injury (infarct size, apoptosis, and inflammation) or enhance cardiac function in PM2.5-exposed hearts subjected to IR. The underlying reason for this ineffectiveness was identified as the inability to improve mitochondrial bioenergetic function and the expression of the declined master regulator gene Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α). Additionally, the compromised mitochondrial quality control genes resulting from PM2.5 exposure could not be restored to their normal levels by these conventional strategies. Furthermore, the crucial pro-survival signaling pathways like phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) could not be reactivated by these strategies in PM2.5-exposed hearts undergoing IR, consequently preventing the restoration of cardioprotection. From the above results, we deduce that the therapeutic benefits of mechanical conditioning techniques such as IPC and POC were compromised in hearts exposed to PM2.5, primarily attributed to PM2.5 induced mitochondrial dysfunction.
期刊介绍：
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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