Duygu Kizir, Esra Nur Yeşilkent, Neslihan Öztürk, Medine Sibel Karağaç, Murat Isıyel, Hilal Tosun, Habibe Karadaş, Hamid Ceylan, Melike Karaman, Yeliz Demir
{"title":"esculetin 对大鼠多柔比星诱导的肝毒性的保护作用：洞察Caspase、FOXOs和热休克蛋白通路的调节作用","authors":"Duygu Kizir, Esra Nur Yeşilkent, Neslihan Öztürk, Medine Sibel Karağaç, Murat Isıyel, Hilal Tosun, Habibe Karadaş, Hamid Ceylan, Melike Karaman, Yeliz Demir","doi":"10.1002/jbt.23861","DOIUrl":null,"url":null,"abstract":"<p>Doxorubicin (DOX) is an anthracycline antibiotic widely employed to treat carcinoma. Nevertheless, severe cardiotoxic side effects restrict its clinical use. Esculetin, a natural flavonoid, is found abundantly in plants. This study evaluated the protective effects of esculetin against DOX-induced hepatotoxicity in rat livers. Forty-eight rats were randomly divided into six groups with eight rats in each group: control (I), DOX (II), esculetin (III, 50 mg/kg), esculetin (IV, 100 mg/kg), DOX+esculetin 50 (V, DOX+esculetin 50 mg/kg), and DOX+esculetin 100 (VI, DOX+esculetin 100 mg/kg). The administration of esculetin effectively mitigated alterations in the measured biochemical parameters induced by DOX. Gene expression analyses demonstrated that esculetin treatment significantly reduced the DOX-induced expression of <i>Foxo1, Hspa1a, Hsp4a, Hsp5a, Casp3,</i> and <i>Casp9</i> while increasing the DOX-induced expression of <i>Foxo3</i>. These findings suggest that esculetin, with its antioxidant and anti-inflammatory effects, might be a therapeutic option for protecting against DOX-induced hepatotoxicity.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The protective effects of esculetin against Doxorubicin-Induced hepatotoxicity in rats: Insights into the modulation of Caspase, FOXOs, and heat shock protein pathways\",\"authors\":\"Duygu Kizir, Esra Nur Yeşilkent, Neslihan Öztürk, Medine Sibel Karağaç, Murat Isıyel, Hilal Tosun, Habibe Karadaş, Hamid Ceylan, Melike Karaman, Yeliz Demir\",\"doi\":\"10.1002/jbt.23861\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Doxorubicin (DOX) is an anthracycline antibiotic widely employed to treat carcinoma. Nevertheless, severe cardiotoxic side effects restrict its clinical use. Esculetin, a natural flavonoid, is found abundantly in plants. This study evaluated the protective effects of esculetin against DOX-induced hepatotoxicity in rat livers. Forty-eight rats were randomly divided into six groups with eight rats in each group: control (I), DOX (II), esculetin (III, 50 mg/kg), esculetin (IV, 100 mg/kg), DOX+esculetin 50 (V, DOX+esculetin 50 mg/kg), and DOX+esculetin 100 (VI, DOX+esculetin 100 mg/kg). The administration of esculetin effectively mitigated alterations in the measured biochemical parameters induced by DOX. Gene expression analyses demonstrated that esculetin treatment significantly reduced the DOX-induced expression of <i>Foxo1, Hspa1a, Hsp4a, Hsp5a, Casp3,</i> and <i>Casp9</i> while increasing the DOX-induced expression of <i>Foxo3</i>. These findings suggest that esculetin, with its antioxidant and anti-inflammatory effects, might be a therapeutic option for protecting against DOX-induced hepatotoxicity.</p>\",\"PeriodicalId\":15151,\"journal\":{\"name\":\"Journal of Biochemical and Molecular Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-09-20\",\"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.23861\",\"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.23861","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
The protective effects of esculetin against Doxorubicin-Induced hepatotoxicity in rats: Insights into the modulation of Caspase, FOXOs, and heat shock protein pathways
Doxorubicin (DOX) is an anthracycline antibiotic widely employed to treat carcinoma. Nevertheless, severe cardiotoxic side effects restrict its clinical use. Esculetin, a natural flavonoid, is found abundantly in plants. This study evaluated the protective effects of esculetin against DOX-induced hepatotoxicity in rat livers. Forty-eight rats were randomly divided into six groups with eight rats in each group: control (I), DOX (II), esculetin (III, 50 mg/kg), esculetin (IV, 100 mg/kg), DOX+esculetin 50 (V, DOX+esculetin 50 mg/kg), and DOX+esculetin 100 (VI, DOX+esculetin 100 mg/kg). The administration of esculetin effectively mitigated alterations in the measured biochemical parameters induced by DOX. Gene expression analyses demonstrated that esculetin treatment significantly reduced the DOX-induced expression of Foxo1, Hspa1a, Hsp4a, Hsp5a, Casp3, and Casp9 while increasing the DOX-induced expression of Foxo3. These findings suggest that esculetin, with its antioxidant and anti-inflammatory effects, might be a therapeutic option for protecting against DOX-induced hepatotoxicity.
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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