Protective Role of Coenzyme Q10 in Modulating Apoptosis, Necrosis, and Autophagy Pathways Induced by Cyclophosphamide in Rat TesticularTissue

Veysel Yüksek; Semiha Dede; Ayşe Usta; Volkan Koşal

Makale detayları

Protective Role of Coenzyme Q10 in Modulating Apoptosis, Necrosis, and Autophagy Pathways Induced by Cyclophosphamide in Rat TesticularTissue

Yazarlar:

Veysel Yüksek | Semiha Dede | Ayşe Usta | Volkan Koşal

Yayıncı:

Igdir University

Ana Başlıklar:

Biyokimya ve Hücre Biyolojisi (Diğer)

Dergi:

Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.15 Issue 3, pp.798-808

Belge Tipi:

Makale

Yayın Tarihi:

1/2025

Belge Dili:

Türkçe

Document ID (Org No.):

2001356713

pISSN:

2536-4618

Anahtar kelimeler:

Özet:

 Cyclophosphamide CPC is one of the oldest anticancer drugs frequently used in cancer treatment. However, CPC is known to have adverse effects on the testis, spermatogenesis, and reproductive hormones. This study aimed to investigate the effect of Coenzyme Q10 CoQ10, a compound naturally found in the testis and seminal fluid and used in infertility treatment, on repairing the damage caused by CPC in testicular tissue. Thirty male Wistar Albino rats were divided into five groups, each consisting of six animals: Control, CPC, CoQ10, CPC  CoQ10-I CQ-I, and CPC  CoQ10-II CQ-II. The mRNA expression levels of junctional genes were detected in apoptotic caspase-8, caspase-9, caspase-3, BAX, BCL2, and BAK1, autophagic ATG3, ATG5, and LC3, and necrotic RIPK1 cell death mechanisms. cDNA was synthesized from total mRNA, and the gene expression levels of apoptosis markers were determined by RT-qPCR. Statistical significance was set at p0.05. CPC was found to upregulate caspase-9, caspase-3, and BAK1 mRNA levels compared to the control group p0.05. However, co-administration of CoQ10 with CPC significantly reduced the expression levels of caspase-9, caspase-3, and BAK1 p0.05. Additionally, a significant increase in BCL-2 gene expression was observed p0.05. CoQ10 treatment reduced the BAXBCL-2 ratio compared to the control and CPC groups p0.05. CPC reduced ATG3 and LC3 mRNA expression, but co-administration of CPC with CoQ10 increased LC3 expression p0.05; additionally, RIPK1 levels were lower in the CQ-I group compared to CPC p0.05. In conclusion, CoQ10 was found to reduce CPC-induced apoptosis, regulate autophagy, and prevent necroptosis, promoting cell survival. However, larger and longer-term studies are required for clinical implementation.

 Cyclophosphamide CPC is one of the oldest anticancer drugs frequently used in cancer treatment. However, CPC is known to have adverse effects on the testis, spermatogenesis, and reproductive hormones. This study aimed to investigate the effect of Coenzyme Q10 CoQ10, a compound naturally found in the testis and seminal fluid and used in infertility treatment, on repairing the damage caused by CPC in testicular tissue. Thirty male Wistar Albino rats were divided into five groups, each consisting of six animals: Control, CPC, CoQ10, CPC  CoQ10-I CQ-I, and CPC  CoQ10-II CQ-II. The mRNA expression levels of junctional genes were detected in apoptotic caspase-8, caspase-9, caspase-3, BAX, BCL2, and BAK1, autophagic ATG3, ATG5, and LC3, and necrotic RIPK1 cell death mechanisms. cDNA was synthesized from total mRNA, and the gene expression levels of apoptosis markers were determined by RT-qPCR. Statistical significance was set at p0.05. CPC was found to upregulate caspase-9, caspase-3, and BAK1 mRNA levels compared to the control group p0.05. However, co-administration of CoQ10 with CPC significantly reduced the expression levels of caspase-9, caspase-3, and BAK1 p0.05. Additionally, a significant increase in BCL-2 gene expression was observed p0.05. CoQ10 treatment reduced the BAXBCL-2 ratio compared to the control and CPC groups p0.05. CPC reduced ATG3 and LC3 mRNA expression, but co-administration of CPC with CoQ10 increased LC3 expression p0.05; additionally, RIPK1 levels were lower in the CQ-I group compared to CPC p0.05. In conclusion, CoQ10 was found to reduce CPC-induced apoptosis, regulate autophagy, and prevent necroptosis, promoting cell survival. However, larger and longer-term studies are required for clinical implementation.

 Cyclophosphamide CPC is one of the oldest anticancer drugs frequently used in cancer treatment. However, CPC is known to have adverse effects on the testis, spermatogenesis, and reproductive hormones. This study aimed to investigate the effect of Coenzyme Q10 CoQ10, a compound naturally found in the testis and seminal fluid and used in infertility treatment, on repairing the damage caused by CPC in testicular tissue. Thirty male Wistar Albino rats were divided into five groups, each consisting of six animals: Control, CPC, CoQ10, CPC  CoQ10-I CQ-I, and CPC  CoQ10-II CQ-II. The mRNA expression levels of junctional genes were detected in apoptotic caspase-8, caspase-9, caspase-3, BAX, BCL2, and BAK1, autophagic ATG3, ATG5, and LC3, and necrotic RIPK1 cell death mechanisms. cDNA was synthesized from total mRNA, and the gene expression levels of apoptosis markers were determined by RT-qPCR. Statistical significance was set at p0.05. CPC was found to upregulate caspase-9, caspase-3, and BAK1 mRNA levels compared to the control group p0.05. However, co-administration of CoQ10 with CPC significantly reduced the expression levels of caspase-9, caspase-3, and BAK1 p0.05. Additionally, a significant increase in BCL-2 gene expression was observed p0.05. CoQ10 treatment reduced the BAXBCL-2 ratio compared to the control and CPC groups p0.05. CPC reduced ATG3 and LC3 mRNA expression, but co-administration of CPC with CoQ10 increased LC3 expression p0.05; additionally, RIPK1 levels were lower in the CQ-I group compared to CPC p0.05. In conclusion, CoQ10 was found to reduce CPC-induced apoptosis, regulate autophagy, and prevent necroptosis, promoting cell survival. However, larger and longer-term studies are required for clinical implementation.

 Siklofosfamid CPC kanser tedavisinde sıklıkla kullanılan en eski antikanser ilaçlarından biridir. CPCnin testis, spermatogenez, üreme hormonları üzerinde olumsuz etkileri olduğu bilinmektedir. Bu çalışma, infertilite tedavisinde kullanılan ve testis ile seminal sıvıda doğal olarak bulunan Koenzim Q10un CoQ10, CPCnin testis dokusunda oluşturduğu hasarın onarılmasına etkisini belirlemeyi amaçlamıştır. 30 Albino Wistar erkek sıçan, her grupta 6 hayvan olacak şekilde 5 gruba Kontrol, Siklofosfamid CPC, Koenzim Q10 CoQ10, CPC  CoQ10-I CQ-I, CPC  CoQ10-II CQ-II ayrıldı. Apoptotik kaspaz-8, kaspaz-9, kaspaz-3, BAX, BCL2, ve BAK1, otofajik ATG3, ATG5 ve LC3 ve nekrotik RIPK1 hücre ölüm mekanizmalarındaki kavşak genlerin mRNA ekspresyon düzeyleri belirlendi. Toplam mRNAdan cDNA sentezlendi. mRNA gen ekspresyon seviyeleri RT-qPCR ile tespit edildi. Tüm grup çalışmaları için p0.05 istatistiksel olarak anlamlı kabul edildi. CPCnin kontrol grubuna göre kaspaz-9, kaspaz-3 ve BAK1 mRNA düzeylerini artırdığı tespit edilmiştir p0.05. CPC ile birlikte CoQ10 uygulandığında, kaspaz-9, kaspaz-3 ve BAK1 genlerinin ekspresyon seviyelerini düşürdüğü p0.05 tespit edilmiştir. Ayrıca, BCL-2 gen ekspresyonunda istatistiksel olarak anlamlı bir artış p0.05 gözlemlenmiştir. Hem kontrol grubuna hem de CPC grubuna kıyasla CoQ10 uygulamasının BAXBCL-2 oranını istatistiksel olarak azalttığı p0.05 ortaya konulmuştur. CPC, ATG3 ve LC3 mRNA ekspresyonunu düşürmüş, ancak CPC ile birlikte CoQ10 uygulaması LC3 ekspresyonunu artırmıştır p0.05; ayrıca RIPK1 seviyesi CQ-I grubunda CPCye göre azalmıştır p0.05. Sonuç olarak, CoQ10un, siklofosfamidin CPC neden olduğu apoptozu düşürdüğü, otofajiyi düzenlendiği ve nekroptozu önlemede rol oynadığı ve hücre sağkalımını desteklediği tespit edilmiştir. Ancak klinik uygulamalar için daha geniş ve uzun vadeli çalışmalar gerekmektedir.

Makale detayları

Protective Role of Coenzyme Q10 in Modulating Apoptosis, Necrosis, and Autophagy Pathways Induced by Cyclophosphamide in Rat TesticularTissue

Yazarlar:

Veysel Yüksek | Semiha Dede | Ayşe Usta | Volkan Koşal

Yayıncı:

Igdir University

Ana Başlıklar:

Biyokimya ve Hücre Biyolojisi (Diğer)

Dergi:

Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.15 Issue 3, pp.798-808

Belge Tipi:

Makale

Yayın Tarihi:

1/2025

Belge Dili:

Türkçe

Document ID (Org No.):

2001356713

pISSN:

2536-4618

Cyclophosphamide

Coenzyme Q10

Caspase-3

Caspase-9

ATG3

LC3Siklofosfamid

KoenzimQ10

Kaspaz-3

Kaspaz-9

ATG3

LC3

Sayı

Makale detayları

Yazarlar: Veysel Yüksek | Semiha Dede | Ayşe Usta | Volkan Koşal

Yayıncı: Igdir University

Ana Başlıklar: Biyokimya ve Hücre Biyolojisi (Diğer)

Dergi: Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.15 Issue 3, pp.798-808

Belge Tipi: Makale

Yayın Tarihi: 1/2025

Belge Dili: Türkçe

Document ID (Org No.): 2001356713

pISSN: 2536-4618

Sayı

Yazarlar:

Veysel Yüksek | Semiha Dede | Ayşe Usta | Volkan Koşal

Yayıncı:

Igdir University

Ana Başlıklar:

Biyokimya ve Hücre Biyolojisi (Diğer)

Dergi:

Iğdır Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.15 Issue 3, pp.798-808

Belge Tipi:

Makale

Yayın Tarihi:

1/2025

Belge Dili:

Türkçe

Document ID (Org No.):

2001356713

pISSN:

2536-4618