Iranian Journal of War and Public Health

en Cardioprotective Potential of Celastrol in Sepsis-Induced Cardiotoxicity; Mouse Model of Endotoxemia تشخیص و درمان بیماری‌های جانبازان يا معلولان Diagnosis and Treatment of Veterans or Handicapped Diseases پژوهشی اصيل Original Research Aims: The study aimed to assess the cardioprotective potential of celastrol against cardiac injury induced by sepsis via amelioration of IL6, TNF, TLR4, IL10, F2-isoprostane, cardiac troponin, and CK-MB, as well as at histological level. Materials & Methods: Twenty-four Swiss albino mice aged between 6 and 8 weeks, weighted between 20 and 30g, were included and were randomly divided into four groups; Sham, Sepsis (laparotomy with CLP), Vehicle (treated with the equivalent volume of DMSO), and celastrol (treated with 2mg/kg IP 1hr before CLP) groups. By spectrophotometric assay, blood samples were then aspirated for cardiac troponin and CK-MB assessment. Part of the cardiac tissue was used to assess the levels of TNFα, IL6, IL10, F2-Isoprostane, and TLR4 by ELISA method; another part was used to assess the degree of cardiac tissue damage by histopathological analysis. Findings: Significant cardiac damage was noticed in the sepsis group (p≤0.05) as compared with the sham group, manifested by a significant elevation in inflammatory markers (TNFα, IL6, TLR4) and oxidative stress marker (F2-Isoprostane) as well as cardiac troponin and CK-MB, with a significant reduction in IL10. Pretreatment with celastrol resulted in a significant reduction in TNF, IL6, TLR4, F2-Isoprostane, troponin, and CK-MB with significant elevation in IL10 compared to the sepsis group. In the same manner, significant histological damage was encountered in the sepsis group compared to the sham group, while the celastrol-treated group exhibited minor histological damage compared to the sepsis group. Conclusion: Celastrol has cardio-protective effects against cardiac injury induced by endotoxemia. Celastrol,Sepsis,Troponin,TLR-4, 361 367 http://ijwph.ir/browse.php?a_code=A-10-1857-10&slc_lang=en&sid=1 F.A. Ghafil 15300319475328460027493 15300319475328460027493 No Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Kufa, Najaf, Iraq E.S. Hassan 15300319475328460027494 15300319475328460027494 Yes Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Kufa, Najaf, Iraq N.D. Aziz 15300319475328460027495 15300319475328460027495 No Department of Clinical Pharmacy, Collage of Pharmacy, University of Kerbala, Kerbala, Iraq M.M. Salim 15300319475328460027496 15300319475328460027496 No Department of Clinical Pathology, Faculty of Medicine, University of Kufa, Najaf, Iraq S.A. Majeed 15300319475328460027497 15300319475328460027497 No Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Kufa, Najaf, Iraq S.M.H. Rasheed 15300319475328460027498 15300319475328460027498 No Department of Clinical Microbiology, Faculty of Medicine, University of Kufa, Najaf, Iraq H.W. Mardan 15300319475328460027499 15300319475328460027499 No Middle Euphrates Center of Neurosciences, Al-Sadder Teaching Hospital, Al-Najaf Al-Ashraf Health Directorate, Najaf, Iraq