Hesham M. Hassan , Aqsa Bibi , Muhammad Faisal Hayat , Khalid J. Alzahrani , Fuad M. Alzahrani , Meshari A. Alsuwat , Maha A. Al-Aream
{"title":"azaleatin通过靶向TLR4/MyD88、JAK1/STAT3和NF-κB对亚砷酸钠诱导的Sprague Dawley大鼠亚慢性心脏毒性的心脏保护作用","authors":"Hesham M. Hassan , Aqsa Bibi , Muhammad Faisal Hayat , Khalid J. Alzahrani , Fuad M. Alzahrani , Meshari A. Alsuwat , Maha A. Al-Aream","doi":"10.1016/j.jtemb.2025.127763","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Sodium arsenite (SA) is a potent carcinogenic compound which is evident to prompt multiple organs damage including the heart. Azaleatin (AZA) is a novel therapeutic agent with excellent biological properties.</div></div><div><h3>Objectives</h3><div>The current investigation was executed to evaluate the mitigative efficacy of AZA against SA induced sub-chronic cardiotoxicity in rats through the evaluation of biochemical and histological parameters.</div></div><div><h3>Methodology</h3><div>Thirty-two rats were apportioned into control, SA (10 mg kg<sup>−1</sup>), SA (10 mg kg<sup>−1</sup>) + AZA (25 mg kg<sup>−1</sup>), and AZA (25 mg kg<sup>−1</sup>) exposed group. Biochemical parameters were evaluated through different techniques including qRT-PCR, ELISA and already reported standard assays. Histological analysis was performed to validate the tissue damage. The curative potential of AZA was re-validated through in-silico approaches.</div></div><div><h3>Findings</h3><div>SA intoxication upregulated the expression of nuclear factor-kappa B (NF-κB), myeloid differentiation primary response 88 (MyD88), janus kinase 1 (JAK1), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), signal transducer and activator of transcription 3 (STAT3), interleukin-1β (IL-1β), interleukin-6 (IL-6), & cyclooxygenase-2 (COX-2) while increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Moreover, the enzymatic activities glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), heme-oxygenase-1 (HO-1) and glutathione (GSH) were lowered whereas the levels of Troponin I, ProBNP, C-reactive protein, LDH, troponin-T, BNP and CPK were exacerbated following the SA exposure. Furthermore, SA intoxication promoted the levels of Bax, Caspase-9, and Caspase-3 while lowering the levels of Bcl-2. Cardiac tissues showed impaired histology after SA administration. Nonetheless, AZA therapy excellently ameliorated cardiac toxicity owing to its anti-inflammatory, antioxidative and anti-apoptotic potential.</div></div><div><h3>Conclusion</h3><div>SA intoxication induced severe cardiac toxicity via disrupting biochemical and histological parameters while AZA excellently restored cardiac health profile. Collectively, AZA may serve as a cardioprotective agent in counteracting SA induced sub-chronic cardiotoxicity.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"92 ","pages":"Article 127763"},"PeriodicalIF":3.6000,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cardioprotective potential of azaleatin against sodium arsenite instigated sub-chronic cardiotoxicity via targeting TLR4/MyD88, JAK1/STAT3, and NF-κB in Sprague Dawley rats\",\"authors\":\"Hesham M. Hassan , Aqsa Bibi , Muhammad Faisal Hayat , Khalid J. Alzahrani , Fuad M. Alzahrani , Meshari A. Alsuwat , Maha A. Al-Aream\",\"doi\":\"10.1016/j.jtemb.2025.127763\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Sodium arsenite (SA) is a potent carcinogenic compound which is evident to prompt multiple organs damage including the heart. Azaleatin (AZA) is a novel therapeutic agent with excellent biological properties.</div></div><div><h3>Objectives</h3><div>The current investigation was executed to evaluate the mitigative efficacy of AZA against SA induced sub-chronic cardiotoxicity in rats through the evaluation of biochemical and histological parameters.</div></div><div><h3>Methodology</h3><div>Thirty-two rats were apportioned into control, SA (10 mg kg<sup>−1</sup>), SA (10 mg kg<sup>−1</sup>) + AZA (25 mg kg<sup>−1</sup>), and AZA (25 mg kg<sup>−1</sup>) exposed group. Biochemical parameters were evaluated through different techniques including qRT-PCR, ELISA and already reported standard assays. Histological analysis was performed to validate the tissue damage. The curative potential of AZA was re-validated through in-silico approaches.</div></div><div><h3>Findings</h3><div>SA intoxication upregulated the expression of nuclear factor-kappa B (NF-κB), myeloid differentiation primary response 88 (MyD88), janus kinase 1 (JAK1), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), signal transducer and activator of transcription 3 (STAT3), interleukin-1β (IL-1β), interleukin-6 (IL-6), & cyclooxygenase-2 (COX-2) while increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Moreover, the enzymatic activities glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), heme-oxygenase-1 (HO-1) and glutathione (GSH) were lowered whereas the levels of Troponin I, ProBNP, C-reactive protein, LDH, troponin-T, BNP and CPK were exacerbated following the SA exposure. Furthermore, SA intoxication promoted the levels of Bax, Caspase-9, and Caspase-3 while lowering the levels of Bcl-2. Cardiac tissues showed impaired histology after SA administration. Nonetheless, AZA therapy excellently ameliorated cardiac toxicity owing to its anti-inflammatory, antioxidative and anti-apoptotic potential.</div></div><div><h3>Conclusion</h3><div>SA intoxication induced severe cardiac toxicity via disrupting biochemical and histological parameters while AZA excellently restored cardiac health profile. Collectively, AZA may serve as a cardioprotective agent in counteracting SA induced sub-chronic cardiotoxicity.</div></div>\",\"PeriodicalId\":49970,\"journal\":{\"name\":\"Journal of Trace Elements in Medicine and Biology\",\"volume\":\"92 \",\"pages\":\"Article 127763\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-09-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Trace Elements in Medicine and Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0946672X25001762\",\"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 Trace Elements in Medicine and Biology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0946672X25001762","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Cardioprotective potential of azaleatin against sodium arsenite instigated sub-chronic cardiotoxicity via targeting TLR4/MyD88, JAK1/STAT3, and NF-κB in Sprague Dawley rats
Background
Sodium arsenite (SA) is a potent carcinogenic compound which is evident to prompt multiple organs damage including the heart. Azaleatin (AZA) is a novel therapeutic agent with excellent biological properties.
Objectives
The current investigation was executed to evaluate the mitigative efficacy of AZA against SA induced sub-chronic cardiotoxicity in rats through the evaluation of biochemical and histological parameters.
Methodology
Thirty-two rats were apportioned into control, SA (10 mg kg−1), SA (10 mg kg−1) + AZA (25 mg kg−1), and AZA (25 mg kg−1) exposed group. Biochemical parameters were evaluated through different techniques including qRT-PCR, ELISA and already reported standard assays. Histological analysis was performed to validate the tissue damage. The curative potential of AZA was re-validated through in-silico approaches.
Findings
SA intoxication upregulated the expression of nuclear factor-kappa B (NF-κB), myeloid differentiation primary response 88 (MyD88), janus kinase 1 (JAK1), toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), signal transducer and activator of transcription 3 (STAT3), interleukin-1β (IL-1β), interleukin-6 (IL-6), & cyclooxygenase-2 (COX-2) while increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Moreover, the enzymatic activities glutathione peroxidase (GPx), glutathione reductase (GSR), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), heme-oxygenase-1 (HO-1) and glutathione (GSH) were lowered whereas the levels of Troponin I, ProBNP, C-reactive protein, LDH, troponin-T, BNP and CPK were exacerbated following the SA exposure. Furthermore, SA intoxication promoted the levels of Bax, Caspase-9, and Caspase-3 while lowering the levels of Bcl-2. Cardiac tissues showed impaired histology after SA administration. Nonetheless, AZA therapy excellently ameliorated cardiac toxicity owing to its anti-inflammatory, antioxidative and anti-apoptotic potential.
Conclusion
SA intoxication induced severe cardiac toxicity via disrupting biochemical and histological parameters while AZA excellently restored cardiac health profile. Collectively, AZA may serve as a cardioprotective agent in counteracting SA induced sub-chronic cardiotoxicity.
期刊介绍:
The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods.
Also, we only publish those articles in which the quality assurance regarding the execution of experiments and achievement of results is guaranteed.