Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death

GOKÇIMEN, ALPASLAN; Bayrak, Erhan; Gurses, Kadri Murat; Birtekocak, Fatih; Gencer, Cevat

doi:10.4274/meandros.galenos.2023.81084

Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death

Cevat Gencer, (Aydın Adnan Menderes Üniversitesi Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, Aydın, Türkiye)

Alpaslan GÖKÇİMEN, (Aydın Adnan Menderes Üniversitesi Tıp Fakültesi, Histoloji ve Embriyoloji Anabilim Dalı, Aydın, Türkiye)

Erhan BAYRAK, (Sivas Numune Hastanesi, Histoloji ve Embriyoloji Kliniği, Sivas, Türkiye)

Fatih BİRTEKOCAK, (Aydın Adnan Menderes Üniversitesi Tıp Fakültesi Biyokimya Anabilim Dalı, Aydın, Türkiye)

Kadri Murat GÜRSES (Selçuk Üniversitesi Tıp Fakültesi, Kardiyoloji Anabilim Dalı, Konya, Türkiye)

Meandros Medical And Dental Journal

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Yıl: 2023 Cilt: 24 Sayı: 2 Sayfa Aralığı: 148 - 154 Metin Dili: İngilizce DOI: 10.4274/meandros.galenos.2023.81084 İndeks Tarihi: 26-07-2023

Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death

Öz:

Objective: The liver is one of the most important internal organs in the human body and has high regenerative properties. It performs the functions of protein synthesis, intake, storage, and distribution of nutrients and vitamins from the blood. In this study, we investigated the curative effect of metformin (Met) on doxorubicin (DOX)-induced liver damage. Materials and Methods: A total of 32 Wistar-albino rats were divided into four groups: control, Met, DOX, and DOX + Met groups. The DOX and DOX + Met groups received four doses of DOX. Met was gavaged daily for 15 days in the DOX + Met and Met groups. Structural liver injury was evaluated with hematoxylin-eosin, picro-sirius, TUNEL, and nuclear factor kB (NF-kB) antibody staining. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total antioxidative status (TAS), total oxidative status (TOS), and hydroxyproline levels were measured as biochemical parameters. Results: The DOX group was found to have a significant structural liver injury characterized by hyperchromatic nuclei in hepatocytes, widespread sinusoidal dilatations, and granular and vacuolar degeneration. Increased NF-kB staining and the apoptotic index were also detected in the DOX group. Biochemical tests revealed an increase in ALT, AST, and TOS levels and a decrease in TAS levels in the DOX group. Met administration provided a significant improvement in the structural changes caused by DOX. In addition, the DOX + Met group had lower NF-kB staining, apoptotic index, ALT, and TOS levels and a higher TAS level compared to the DOX group. Conclusion: Our findings indicate that Met alleviates DOX-induced structural liver injury by reducing oxidative stress, inflammation, and excessive cell death.

Anahtar Kelime:

Metformin, Sıçanlarda Oksidatif Stresi, Enflamasyonu ve Aşırı Hücre Ölümünü Azaltarak Doksorubisin Kaynaklı Karaciğer Hasarını Azaltır

Öz:

Amaç: Karaciğer, yenilenme özelliği yüksek olan insan vücudundaki en önemli iç organlardan biridir. Protein sentezi, besin maddelerinin ve vitaminlerin kandan alınması, depolanması ve dağıtılması işlevlerini yerine getirmektedir. Bu araştırmada, doksorubisin (DOX) ile oluşturulan karaciğer hasarı üzerindeki metforminin (Met) iyileştirici etkisinin araştırılması amaçlanmıştır. Gereç ve Yöntemler: Toplam 32 Wistar-albino sıçan dört gruba ayrıldı: kontrol, Met, DOX ve DOX + Met grupları. DOX ve DOX + Met gruplarına dört doz DOX verildi. DOX + Met ve Met gruplarında 15 gün süreyle günde Met verildi. Yapısal karaciğer hasarı, hematoksilen-eozin, pikro-sirius, TUNEL ve nükleer faktör kB (NF-kB) antikor boyaması ile değerlendirildi. Biyokimyasal değerlendirmeler için alanin aminotransferaz (ALT), aspartat aminotransferaz (AST), total antioksidan durum (TAS), total oksidatif durum (TOS) ve hidroksiprolin düzeyleri ölçüldü. Bulgular: DOX grubunda, hepatositlerde hiperkromatik çekirdekler, yaygın sinüzoidal dilatasyonlar, granüler ve vakuoler dejenerasyon ile karakterize önemli yapısal karaciğer hasarı olduğu bulundu. DOX grubunda artmış NF-kB boyama ve apoptotik indeks de tespit edildi. Biyokimyasal testler DOX grubunda ALT, AST ve TOS düzeylerinde artış ve TAS düzeyinde azalma gösterdi. Met uygulaması,DOX’un neden olduğu yapısal değişikliklerde belirgin bir iyileşme sağladığı gözlemlenmiştir. Ayrıca DOX + Met grubunda DOX grubuna göre NF-kB boyama, apoptotik indeks, ALT ve TOS düzeyleri daha düşük ve TAS düzeyi daha yüksekti. Sonuç: Bulgularımız, Met’in oksidatif stresi, enflamasyonu ve aşırı hücre ölümünü azaltarak DOX kaynaklı yapısal karaciğer hasarının etkisini hafiflettiğini göstermektedir.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	Gencer C, GOKÇIMEN A, Bayrak E, Birtekocak F, Gurses K (2023). Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death. , 148 - 154. 10.4274/meandros.galenos.2023.81084
Chicago	Gencer Cevat,GOKÇIMEN ALPASLAN,Bayrak Erhan,Birtekocak Fatih,Gurses Kadri Murat Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death. (2023): 148 - 154. 10.4274/meandros.galenos.2023.81084
MLA	Gencer Cevat,GOKÇIMEN ALPASLAN,Bayrak Erhan,Birtekocak Fatih,Gurses Kadri Murat Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death. , 2023, ss.148 - 154. 10.4274/meandros.galenos.2023.81084
AMA	Gencer C,GOKÇIMEN A,Bayrak E,Birtekocak F,Gurses K Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death. . 2023; 148 - 154. 10.4274/meandros.galenos.2023.81084
Vancouver	Gencer C,GOKÇIMEN A,Bayrak E,Birtekocak F,Gurses K Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death. . 2023; 148 - 154. 10.4274/meandros.galenos.2023.81084
IEEE	Gencer C,GOKÇIMEN A,Bayrak E,Birtekocak F,Gurses K "Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death." , ss.148 - 154, 2023. 10.4274/meandros.galenos.2023.81084
ISNAD	Gencer, Cevat vd. "Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death". (2023), 148-154. https://doi.org/10.4274/meandros.galenos.2023.81084

APA	Gencer C, GOKÇIMEN A, Bayrak E, Birtekocak F, Gurses K (2023). Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death. Meandros Medical And Dental Journal, 24(2), 148 - 154. 10.4274/meandros.galenos.2023.81084
Chicago	Gencer Cevat,GOKÇIMEN ALPASLAN,Bayrak Erhan,Birtekocak Fatih,Gurses Kadri Murat Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death. Meandros Medical And Dental Journal 24, no.2 (2023): 148 - 154. 10.4274/meandros.galenos.2023.81084
MLA	Gencer Cevat,GOKÇIMEN ALPASLAN,Bayrak Erhan,Birtekocak Fatih,Gurses Kadri Murat Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death. Meandros Medical And Dental Journal, vol.24, no.2, 2023, ss.148 - 154. 10.4274/meandros.galenos.2023.81084
AMA	Gencer C,GOKÇIMEN A,Bayrak E,Birtekocak F,Gurses K Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death. Meandros Medical And Dental Journal. 2023; 24(2): 148 - 154. 10.4274/meandros.galenos.2023.81084
Vancouver	Gencer C,GOKÇIMEN A,Bayrak E,Birtekocak F,Gurses K Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death. Meandros Medical And Dental Journal. 2023; 24(2): 148 - 154. 10.4274/meandros.galenos.2023.81084
IEEE	Gencer C,GOKÇIMEN A,Bayrak E,Birtekocak F,Gurses K "Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death." Meandros Medical And Dental Journal, 24, ss.148 - 154, 2023. 10.4274/meandros.galenos.2023.81084
ISNAD	Gencer, Cevat vd. "Metformin Alleviates Doxorubicin-induced Liver Injury in Rats via Reducing Oxidative Stress, inflammation and Excessive Cell Death". Meandros Medical And Dental Journal 24/2 (2023), 148-154. https://doi.org/10.4274/meandros.galenos.2023.81084