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

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 o...

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Main Authors: İlknur Bingül, Canan Küçükgergin, Asiye Işın Doğan Ekici, Semra Doğru Abbasoğlu, Mehmet Müjdat Uysal
Format: Article
Language:English
Published: Istanbul University Press 2024-01-01
Series:İstanbul Tıp Fakültesi Dergisi
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Online Access:https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/C69D8D8E34F84D2983EC84D6DF81E0A2
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author İlknur Bingül
Canan Küçükgergin
Asiye Işın Doğan Ekici
Semra Doğru Abbasoğlu
Mehmet Müjdat Uysal
author_facet İlknur Bingül
Canan Küçükgergin
Asiye Işın Doğan Ekici
Semra Doğru Abbasoğlu
Mehmet Müjdat Uysal
author_sort İlknur Bingül
collection DOAJ
description 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 DMF+EtOH. Rats were administered EtOH (4.5 g/kg orally, 3 doses with 12-h intervals). DMF (30 mg/kg; gavage) was applied to rats 1 hour before each application of EtOH in the DMF+EtOH 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 DMF+EtOH 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.
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institution Kabale University
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publishDate 2024-01-01
publisher Istanbul University Press
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series İstanbul Tıp Fakültesi Dergisi
spelling doaj-art-8e08b9595d4a4010a4f3f6fef629517f2025-08-20T03:52:47ZengIstanbul University Pressİstanbul Tıp Fakültesi Dergisi1305-64412024-01-01871112010.26650/IUITFD.1344655123456NRF2 ACTIVATOR DIMETHYL FUMARATE DIMINISHED STEATOSIS, INFLAMMATION AND LIPID PEROXIDATION IN THE LIVER OF BINGE ETHANOL-TREATED RATSİlknur Bingül0https://orcid.org/0000-0002-6432-3541Canan Küçükgergin1https://orcid.org/0000-0002-1797-5889Asiye Işın Doğan Ekici2https://orcid.org/0000-0003-4062-9519Semra Doğru Abbasoğlu3https://orcid.org/0000-0003-3467-9763Mehmet Müjdat Uysal4https://orcid.org/0000-0002-8802-8766İstanbul Üniversitesi, İstanbul, Türkiyeİstanbul Üniversitesi, İstanbul, TürkiyeAcıbadem Üniversitesi, İstanbul, Türkiyeİstanbul Üniversitesi, İstanbul, Türkiyeİstanbul Üniversitesi, İstanbul, TürkiyeObjective: 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 DMF+EtOH. Rats were administered EtOH (4.5 g/kg orally, 3 doses with 12-h intervals). DMF (30 mg/kg; gavage) was applied to rats 1 hour before each application of EtOH in the DMF+EtOH 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 DMF+EtOH 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.https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/C69D8D8E34F84D2983EC84D6DF81E0A2dimethyl fumaratenuclear factor erythroid 2-related factorethanolliver damageoxidative stress
spellingShingle İlknur Bingül
Canan Küçükgergin
Asiye Işın Doğan Ekici
Semra Doğru Abbasoğlu
Mehmet Müjdat Uysal
NRF2 ACTIVATOR DIMETHYL FUMARATE DIMINISHED STEATOSIS, INFLAMMATION AND LIPID PEROXIDATION IN THE LIVER OF BINGE ETHANOL-TREATED RATS
İstanbul Tıp Fakültesi Dergisi
dimethyl fumarate
nuclear factor erythroid 2-related factor
ethanol
liver damage
oxidative stress
title NRF2 ACTIVATOR DIMETHYL FUMARATE DIMINISHED STEATOSIS, INFLAMMATION AND LIPID PEROXIDATION IN THE LIVER OF BINGE ETHANOL-TREATED RATS
title_full NRF2 ACTIVATOR DIMETHYL FUMARATE DIMINISHED STEATOSIS, INFLAMMATION AND LIPID PEROXIDATION IN THE LIVER OF BINGE ETHANOL-TREATED RATS
title_fullStr NRF2 ACTIVATOR DIMETHYL FUMARATE DIMINISHED STEATOSIS, INFLAMMATION AND LIPID PEROXIDATION IN THE LIVER OF BINGE ETHANOL-TREATED RATS
title_full_unstemmed NRF2 ACTIVATOR DIMETHYL FUMARATE DIMINISHED STEATOSIS, INFLAMMATION AND LIPID PEROXIDATION IN THE LIVER OF BINGE ETHANOL-TREATED RATS
title_short NRF2 ACTIVATOR DIMETHYL FUMARATE DIMINISHED STEATOSIS, INFLAMMATION AND LIPID PEROXIDATION IN THE LIVER OF BINGE ETHANOL-TREATED RATS
title_sort nrf2 activator dimethyl fumarate diminished steatosis inflammation and lipid peroxidation in the liver of binge ethanol treated rats
topic dimethyl fumarate
nuclear factor erythroid 2-related factor
ethanol
liver damage
oxidative stress
url https://cdn.istanbul.edu.tr/file/JTA6CLJ8T5/C69D8D8E34F84D2983EC84D6DF81E0A2
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