NRF2 ACTIVATOR DIMETHYL FUMARATE DIMINISHED STEATOSIS, INFLAMMATION AND LIPID PEROXIDATION IN THE LIVER OF BINGE ETHANOL-TREATED RATS

İlknur Bingül; Canan Küçükgergin; Asiye Işın Doğan Ekici; Semra Doğru Abbasoğlu; Müjdat Uysal

Makale detayları

NRF2 ACTIVATOR DIMETHYL FUMARATE DIMINISHED STEATOSIS, INFLAMMATION AND LIPID PEROXIDATION IN THE LIVER OF BINGE ETHANOL-TREATED RATS

Yazarlar:

İlknur Bingül | Canan Küçükgergin | Asiye Işın Doğan Ekici | Semra Doğru Abbasoğlu | Müjdat Uysal

Yayıncı:

Istanbul University

Ana Başlıklar:

Sağlık Hizmetleri ve Sistemleri (Diğer)

Dergi:

İstanbul Tıp Fakültesi Dergisi Vol.87 Issue 1, pp.11-20

Belge Tipi:

Makale

Yayın Tarihi:

1/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001314929

pISSN:

1305-6441

Anahtar kelimeler:

Özet:

 Objective: This study was conducted to explore the impact of dimethyl fumarate DMF, which has antioxidant and anti-inflammatory effects, on binge ethanol EtOH-induced hepatic steatosis, inflammation, and lipid peroxidation in rats. Material and Method: To examine the potential protective effect of DMF against EtOH-induced hepatic damage, rats were divided into four groups control, DMF, EtOH, and DMFEtOH. Rats were administered EtOH 4.5 gkg orally, 3 doses with 12-h intervals. DMF 30 mgkg; gavage was applied to rats 1 hour before each application of EtOH in the DMFEtOH group. Serum markers of liver damage, triglyceride TG, tumor necrosis factor-alpha TNF-α, lipid and protein oxidation products, myeloperoxidase MPO, and antioxidant enzymes together with histopathological examinations were performed in liver tissue. Protein expressions associated with antioxidant mechanism nuclear factor erythroid 2-related factor; Nrf2 and heme oxygenase- 1; HO-1, lipid metabolism sterol regulatory element-binding protein-1c; SREBP-1c and peroxisome proliferator-activated receptor-alpha; PPAR-α, oxidative stress cytochrome P4502E1; CYP2E1, and inflammation nuclear factor-kappa B; NF-κB were also investigated in the rats livers. Result: DMF reduced elevated levels of serum markers of liver damage and hepatic TG, TNF-α and reactive oxygen species levels, lipid and protein oxidation products, and MPO activity together with the alleviation of histopathological lesions in EtOH-treated rats. Increased Nrf2 and HO-1 and decreased SREBP-1c and CYP2E1 expressions were also detected in the DMFEtOH group compared with the EtOH group. Conclusion: Our results demonstrate that DMF may provide a protective effect against EtOH-induced hepatic lesions. These outcomes may be linked to the anti-oxidative, anti-inflammatory, and anti-lipogenic potential of DMF-induced Nrf2 activation.

 Objective: This study was conducted to explore the impact of dimethyl fumarate DMF, which has antioxidant and anti-inflammatory effects, on binge ethanol EtOH-induced hepatic steatosis, inflammation, and lipid peroxidation in rats. Material and Method: To examine the potential protective effect of DMF against EtOH-induced hepatic damage, rats were divided into four groups control, DMF, EtOH, and DMFEtOH. Rats were administered EtOH 4.5 gkg orally, 3 doses with 12-h intervals. DMF 30 mgkg; gavage was applied to rats 1 hour before each application of EtOH in the DMFEtOH group. Serum markers of liver damage, triglyceride TG, tumor necrosis factor-alpha TNF-α, lipid and protein oxidation products, myeloperoxidase MPO, and antioxidant enzymes together with histopathological examinations were performed in liver tissue. Protein expressions associated with antioxidant mechanism nuclear factor erythroid 2-related factor; Nrf2 and heme oxygenase- 1; HO-1, lipid metabolism sterol regulatory element-binding protein-1c; SREBP-1c and peroxisome proliferator-activated receptor-alpha; PPAR-α, oxidative stress cytochrome P4502E1; CYP2E1, and inflammation nuclear factor-kappa B; NF-κB were also investigated in the rats livers. Result: DMF reduced elevated levels of serum markers of liver damage and hepatic TG, TNF-α and reactive oxygen species levels, lipid and protein oxidation products, and MPO activity together with the alleviation of histopathological lesions in EtOH-treated rats. Increased Nrf2 and HO-1 and decreased SREBP-1c and CYP2E1 expressions were also detected in the DMFEtOH group compared with the EtOH group. Conclusion: Our results demonstrate that DMF may provide a protective effect against EtOH-induced hepatic lesions. These outcomes may be linked to the anti-oxidative, anti-inflammatory, and anti-lipogenic potential of DMF-induced Nrf2 activation.

 Objective: This study was conducted to explore the impact of dimethyl fumarate DMF, which has antioxidant and anti-inflammatory effects, on binge ethanol EtOH-induced hepatic steatosis, inflammation, and lipid peroxidation in rats. Material and Method: To examine the potential protective effect of DMF against EtOH-induced hepatic damage, rats were divided into four groups control, DMF, EtOH, and DMFEtOH. Rats were administered EtOH 4.5 gkg orally, 3 doses with 12-h intervals. DMF 30 mgkg; gavage was applied to rats 1 hour before each application of EtOH in the DMFEtOH group. Serum markers of liver damage, triglyceride TG, tumor necrosis factor-alpha TNF-α, lipid and protein oxidation products, myeloperoxidase MPO, and antioxidant enzymes together with histopathological examinations were performed in liver tissue. Protein expressions associated with antioxidant mechanism nuclear factor erythroid 2-related factor; Nrf2 and heme oxygenase- 1; HO-1, lipid metabolism sterol regulatory element-binding protein-1c; SREBP-1c and peroxisome proliferator-activated receptor-alpha; PPAR-α, oxidative stress cytochrome P4502E1; CYP2E1, and inflammation nuclear factor-kappa B; NF-κB were also investigated in the rats livers. Result: DMF reduced elevated levels of serum markers of liver damage and hepatic TG, TNF-α and reactive oxygen species levels, lipid and protein oxidation products, and MPO activity together with the alleviation of histopathological lesions in EtOH-treated rats. Increased Nrf2 and HO-1 and decreased SREBP-1c and CYP2E1 expressions were also detected in the DMFEtOH group compared with the EtOH group. Conclusion: Our results demonstrate that DMF may provide a protective effect against EtOH-induced hepatic lesions. These outcomes may be linked to the anti-oxidative, anti-inflammatory, and anti-lipogenic potential of DMF-induced Nrf2 activation.

 Amaç: Bu çalışma, antioksidan ve anti-inflamatuar etkilere sahip dimetil fumaratın DMF sıçanlarda binge etanol EtOH ile indüklenen karaciğer steatozu, inflamasyon ve lipit peroksidasyonu üzerindeki etkisini araştırmak amacıyla yapıldı. Gereç ve Yöntem: EtOH ile indüklenen karaciğer hasarına karşı DMFnin potansiyel koruyucu etkisini incelemek için sıçanlar kontrol, DMF, EtOH ve DMFEtOH olmak üzere dört gruba ayrıldı. Sıçanlara EtOH 4,5 gkg oral, 12 saat arayla 3 doz verildi. DMFEtOH grubundaki sıçanlara her EtOH uygulamasından 1 saat önce DMF 30 mgkg; gavaj uygulandı. Karaciğer hasarı serum belirteçleri, trigliserid TG, tümör nekroz faktörü-alfa TNF-α, lipid ve protein oksidasyon ürünleri, miyeloperoksidaz MPO ve antioksidan enzimler ile birlikte karaciğer dokusunda histopatolojik incelemeler gerçekleştirildi. Karaciğerde antioksidan mekanizma nükleer faktör eritroid 2 ile ilişkili faktör; Nrf2 ve hem oksijenaz-1; HO-1, lipid metabolizması sterol düzenleyici element bağlayıcı protein-1c; SREBP-1c ve peroksizom proliferatör ile aktive olan reseptör-alfa; PPAR-α oksidatif stres sitokrom P4502E1; CYP2E1 ve inflamasyon nükleer faktör-kappa B; NF- κB ile ilişkili protein ekspresyonları da araştırıldı. Bulgular: DMF, EtOH uygulanan sıçanlarda histopatolojik lezyonların iyileşmesinin yanında artmış serum karaciğer hasarı belirteçlerini, hepatik TG, TNF-α ve reaktif oksijen türleri düzeylerini, lipid ve protein oksidasyon ürünlerini ve MPO aktivitesini de azalttı. DMFEtOH grubunda Nrf2 ve HO-1ekspresyonlarının EtOH grubuna göre arttığı ve SREBP-1c ve CYP2E1 ekspresyonlarının ise EtOH grubuna göre azaldığı saptandı. Sonuç: Sonuçlarımız, DMFnin EtOH tarafından indüklenen karaciğer lezyonlarının oluşumuna karşı koruyucu bir etki sağlayabileceğini göstermektedir. Bu etkiler, DMF ile indüklenen Nrf2 aktivasyonunun antioksidan, anti-inflamatuar ve anti-lipojenik potansiyeli ile ilişkili olabilir.

Makale detayları

NRF2 ACTIVATOR DIMETHYL FUMARATE DIMINISHED STEATOSIS, INFLAMMATION AND LIPID PEROXIDATION IN THE LIVER OF BINGE ETHANOL-TREATED RATS

Yazarlar:

İlknur Bingül | Canan Küçükgergin | Asiye Işın Doğan Ekici | Semra Doğru Abbasoğlu | Müjdat Uysal

Yayıncı:

Istanbul University

Ana Başlıklar:

Sağlık Hizmetleri ve Sistemleri (Diğer)

Dergi:

İstanbul Tıp Fakültesi Dergisi Vol.87 Issue 1, pp.11-20

Belge Tipi:

Makale

Yayın Tarihi:

1/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001314929

pISSN:

1305-6441

Dimethyl fumarate

nuclear factor erythroid 2-related factor

ethanol

liver damage

oxidative stressDimetil fumarat

nükleer faktör eritroid 2 ilişkili faktör

etanol

karaciğer hasarı

oksidatif stres

Sayı

Makale detayları

Yazarlar: İlknur Bingül | Canan Küçükgergin | Asiye Işın Doğan Ekici | Semra Doğru Abbasoğlu | Müjdat Uysal

Yayıncı: Istanbul University

Ana Başlıklar: Sağlık Hizmetleri ve Sistemleri (Diğer)

Dergi: İstanbul Tıp Fakültesi Dergisi Vol.87 Issue 1, pp.11-20

Belge Tipi: Makale

Yayın Tarihi: 1/2024

Belge Dili: İngilizce

Document ID (Org No.): 2001314929

pISSN: 1305-6441

Sayı

Yazarlar:

İlknur Bingül | Canan Küçükgergin | Asiye Işın Doğan Ekici | Semra Doğru Abbasoğlu | Müjdat Uysal

Yayıncı:

Istanbul University

Ana Başlıklar:

Sağlık Hizmetleri ve Sistemleri (Diğer)

Dergi:

İstanbul Tıp Fakültesi Dergisi Vol.87 Issue 1, pp.11-20

Belge Tipi:

Makale

Yayın Tarihi:

1/2024

Belge Dili:

İngilizce

Document ID (Org No.):

2001314929

pISSN:

1305-6441