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

Nurhan Akaras; Özge Kandemir; Hasan Şimşek

Makale detayları

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

Yazarlar:

Nurhan Akaras | Özge Kandemir | Hasan Şimşek

Yayıncı:

Bingol University

Ana Başlıklar:

Biyokimya ve Hücre Biyolojisi (Diğer)

Dergi:

Türk Doğa ve Fen Dergisi Vol.13 Issue 4, pp.180-191

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001336405

pISSN:

2149-6366

Anahtar kelimeler:

Özet:

 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. HE staining results showed that Carvacrol preserved myocardial tissue integrity. In conclusion, Carvacrol showed a cardioprotective effect against cisplatin-induced cardiotoxicity.

 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. HE staining results showed that Carvacrol preserved myocardial tissue integrity. In conclusion, Carvacrol showed a cardioprotective effect against cisplatin-induced cardiotoxicity.

 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. HE staining results showed that Carvacrol preserved myocardial tissue integrity. In conclusion, Carvacrol showed a cardioprotective effect against cisplatin-induced cardiotoxicity.

 Sisplatin esas olarak katı tümörlerin tedavisinde kullanılan en aktif sitotoksik ajanlardan biridir. Sisplatinin yüksek doz ve uzun süreli kullanımı kardiyotoksisiteye neden olduğu bilinmektedir. Son yıllarda kardiyovasküler hastalıklarda Karvakrolün antiapoptotik ve antioksidan etkileri ilgi görmüştür. Bu çalışmada, bir sıçan modelinde Karvakrolün Sisplatin kaynaklı kardiyotoksisite üzerindeki etkileri biyokimyasal ve histolojik yöntemler kullanılarak araştırılmıştır. Yirmi sekiz sıçan 4 gruba ayrıldı: 1. kontrol grubu, 2. Karvakrol grubu, 3. Sisplatin grubu, 4. Sisplatin  Karvakrol grubu. Son ilaç uygulamasından sonra öldürülen sıçanlardan elde edilen kalp dokusunda antioksidan enzimlerin, proinflamatuar sitokinlerin, apoptotik ve otofajik proteinlerin ekspresyonu incelenmiştir. Ayrıca kalp dokusu histopatolojik olarak değerlendirilmiştir. Sisplatinin hayvanların kalp dokusunda oksidatif strese ve inflamatuar hasara neden olduğu gözlenmiştir. Karvakrol uygulamasının antioksidan enzim süperoksit dismutaz ve glutatyon peroksidaz aktivitelerini önemli ölçüde artırırken, inflamatuar belirteçleri NF-κB, TNF-α, IL-1β baskıladı. Ayrıca Sisplatinin apoptotik caspase-3, Bax, Bcl-2 ve otofajik Beclin-1, LC3A, LC3B belirteçleri indükledi. Karvakrolün ise anti-apoptotik ve anti-otofajik etki göstererek kalp dokularını Sisplatinin yıkıcı etkisinden koruyabildiği belirlenmiştir. Sisplatin uygulaması ile azalmış Notch1 ve Hes1 ekspresyon seviyeleri Karvakrol uygulamasından sonra düzenlenmiştir. HE boyama sonuçları Karvakrolün miyokardiyal doku bütünlüğünü koruduğunu göstermiştir. Sonuç olarak, Karvakrol Sisplatin kaynaklı kardiyotoksisiteye karşı kardiyoprotektif bir etki gösterdi.

Makale detayları

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

Yazarlar:

Nurhan Akaras | Özge Kandemir | Hasan Şimşek

Yayıncı:

Bingol University

Ana Başlıklar:

Biyokimya ve Hücre Biyolojisi (Diğer)

Dergi:

Türk Doğa ve Fen Dergisi Vol.13 Issue 4, pp.180-191

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001336405

pISSN:

2149-6366

Cisplatin

Carvacrol

Cardiac Tissue

Oxidative Stress

Apoptosis

RatSisplatin

Karvakrol

Kardiyak Doku

Oksidatif Stres

Apoptozis

Sıçan

Sayı

Makale detayları

Yazarlar: Nurhan Akaras | Özge Kandemir | Hasan Şimşek

Yayıncı: Bingol University

Ana Başlıklar: Biyokimya ve Hücre Biyolojisi (Diğer)

Dergi: Türk Doğa ve Fen Dergisi Vol.13 Issue 4, pp.180-191

Belge Tipi: Makale

Yayın Tarihi: 12/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001336405

pISSN: 2149-6366

Sayı

Yazarlar:

Nurhan Akaras | Özge Kandemir | Hasan Şimşek

Yayıncı:

Bingol University

Ana Başlıklar:

Biyokimya ve Hücre Biyolojisi (Diğer)

Dergi:

Türk Doğa ve Fen Dergisi Vol.13 Issue 4, pp.180-191

Belge Tipi:

Makale

Yayın Tarihi:

12/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001336405

pISSN:

2149-6366