Carvacrol Ameliorates Cisplatin-Induced Cardiotoxicity By Regulating Notch/Hes1 Signaling Pathway, Oxidative Stress and Cell Death In Rat Cardiac Tissue

Authors : Nurhan Akaras, Özge Kandemir, Hasan Şimşek
Pages : 180-191
Doi:10.46810/tdfd.1564047
View : 133 | Download : 105
Publication Date : 2024-12-30
Article Type : Research Paper
Abstract :Cisplatin is one of the most active cytotoxic agents used mainly in the treatment of solid tumors. High doses and long-term use of Cisplatin are known to cause cardiotoxicity. In recent years, the antiapoptotic and antioxidant effects of Carvacrol in cardiovascular diseases have attracted attention. In this study, the effects of Carvacrol on Cisplatin-induced cardiotoxicity in a rat model were investigated using biochemical and histological methods. Twenty-eight rats were divided into 4 groups: 1. Control group, 2. Carvacrol group, 3. Cisplatin group, 4. Cisplatin + Carvacrol group. The expression of antioxidant enzymes, proinflammatory cytokines, apoptotic, and autophagic proteins was examined in heart tissue obtained from rats sacrificed after the last drug administration. Additionally, heart tissue was evaluated histopathologically. Cisplatin has been observed to cause oxidative stress and inflammatory damage in animal heart tissue. Carvacrol administration significantly increased antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities while suppressing inflammatory markers (NF-κB, TNF-α, IL-1β). Additionally, Cisplatin induced apoptotic (caspase-3, Bax, Bcl-2) and autophagic (Beclin-1, LC3A, LC3B) markers. It has been determined that carvacrol can protect heart tissues from the destructive effects of cisplatin by exerting anti-apoptotic and anti-autophagic effects. The expression levels of Notch1 and Hes1, which were decreased by cisplatin administration, were upregulated after administration of Carvacrol. H&E staining results showed that Carvacrol preserved myocardial tissue integrity. In conclusion, Carvacrol showed a cardioprotective effect against cisplatin-induced cardiotoxicity.
Keywords : Sisplatin, Karvakrol, Kardiyak Doku, Oksidatif Stres, Apoptozis, Sıçan

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