CCl4-Induced Liver Injury Was Ameliorated by Qi-Ge Decoction through the Antioxidant Pathway

Qi-Ge decoction (QGD), which is derived from the Huangqi Gegen decoction, contains three traditional Chinese herbs: Astragalus membranaceus (Huangqi), Pueraria lobata (Gegen), and Citri Reticulatae Blanco Pericarpium (Chenpi). Gastric mucosal damage caused by ethanol was prevented and alleviated by QGD. However, the role of QGD in protecting the liver from toxins has not been reported. High-performance liquid chromatography with diode-array detection was used to qualitatively analyze QGD. Positive control (silymarin 100 mg/kg/day), QGD (20, 10, or 5 g/kg/day), and Nrf2 inhibitor brusatol (0.4 mg/kg/2 d) were administered to rats for 7 days, and then, liver injury was induced by injecting 2 mL/kg 25% CCl4. After 24 h, blood and liver were collected for analysis and evaluation. QGD was found to contain 12 main components including calycosin, puerarin, and hesperidin. QGD treatment significantly reduced liver damage and decreased serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase activities. QGD increased superoxide dismutase and catalase activities, and glutathione levels, but decreased malondialdehyde levels in livers from CCl4-treated rats. Compared to rats treated with CCl4 alone, after QGD administration, mRNA and protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 were increased, while those of Kelch-like ECH-related protein 1 (Keap1) and cytochrome P450 (CYP)2E1 were decreased. However, these improvements in QGD were reversed by brusatol. In conclusion, QGD can achieve its hepatoprotective effect through an antioxidant mechanism by activating the Nrf2 pathway.

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Emodin Attenuates Acetaminophen-Induced Hepatotoxicity via Cgas-STING Pathway

10.21203/rs.3.rs-419469/v1 ◽

2021 ◽

Author(s):

Pan Shen ◽

Zhe Cheng ◽

Qiong Liu

Keyword(s):

Liver Injury ◽

Molecular Mechanisms ◽

Inflammatory Responses ◽

Interleukin 1 ◽

Chinese Herbs ◽

Inflammatory Factors ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Neuroprotective Effects ◽

Hepatocellular Damage

Abstract Background: Emodin, a natural bioactive compound from traditional Chinese herbs, exerts anti-inflammatory, anti-oxidants, anticancer, hepatoprotective, and neuroprotective effects. However, its protective effects in acetaminophen (APAP)-induced hepatotoxicity still unclear. Aim: The study explored the effects of emodin on APAP-induced hepatotoxicity and investigated the potential molecular mechanisms. Materials and Methods: C57BL/6 mice with pre-treatment of emodin (15, 30 mg/kg) for consecutive 5 days, then were given APAP (300 mg/kg) to make APAP-induced liver injury model. Mice were sacrificed to detected the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), and the liver tissues levels of glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD). Histological assessment, Western blot and ELISA were conducted. Results: Emodin pretreatment significantly reduced the levels of ALT, AST, and ALP, increased the levels of ALB, alleviated hepatocellular damage and apoptosis, attenuated the exhaustion of GSH, SOD, and accumulation of MDA, increased the expression of antioxidative enzymes, including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and NAD(P)H quinone dehydrogenase 1(NQO1). Additionally, emodin inhibited the expression of NLRP3 and reduced the levels of pro-inflammatory factors, including interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α). Emodin inhibited Cyclic GMP-AMP synthase (cGAS) and its downstream signaling effector stimulator of interferon genes (STING) expression for liver protection against APAP-induced inflammatory responses and apoptosis. Conclusion: The above results suggested that emodin protected hepatocytes from APAP induce liver injury via the up-regulation of Nrf2 mediated anti-oxidative stress pathway, the inhibition of NLRP3 inflammasome, and the down-regulation of the cGAS-STING signaling pathway.

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Hepatoprotective Effect of Polysaccharides Isolated from Dendrobium officinale against Acetaminophen-Induced Liver Injury in Mice via Regulation of the Nrf2-Keap1 Signaling Pathway

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/6962439 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 12

Author(s):

Guosheng Lin ◽

Dandan Luo ◽

Jingjing Liu ◽

Xiaoli Wu ◽

Jinfen Chen ◽

...

Keyword(s):

Liver Injury ◽

Signaling Pathway ◽

Nuclear Translocation ◽

Hepatoprotective Effect ◽

Dendrobium Officinale ◽

Regulatory Subunit ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Glutamate Cysteine Ligase ◽

Nrf2 Signaling Pathway

The effect of polysaccharides isolated from Dendrobium officinale (DOP) on acetaminophen- (APAP-) induced hepatotoxicity and the underlying mechanisms involved are investigated. Male Institute of Cancer Research (ICR) mice were randomly assigned to six groups: (1) control, (2) vehicle (APAP, 230 mg/kg), (3) N-acetylcysteine (100 mg/kg), (4) 50 mg/kg DOP, (5) 100 mg/kg DOP, and (6) 200 mg/kg DOP. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the serum and glutathione (GSH), malondialdehyde (MDA), catalase (CAT), total antioxidant capacity (T-AOC), myeloperoxidase (MPO), and reactive oxygen species (ROS) levels in the liver were determined after the death of the mice. The histological examination of the liver was also performed. The effect of DOP on the Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway was evaluated using Western blot analysis and real-time polymerase chain reaction (PCR). The results showed that DOP treatment significantly alleviated the hepatic injury. The decrease in ALT and AST levels in the serum and ROS, MDA, and MPO contents in the liver, as well as the increases in GSH, CAT, and T-AOC in the liver, were observed after DOP treatment. DOP treatment significantly induced the dissociation of Nrf2 from the Nrf2−Keap1 complex and promoted the Nrf2 nuclear translocation. Subsequently, DOP-mediated Nrf2 activation triggered the transcription and expressions of the glutamate–cysteine ligase catalytic (GCLC) subunit, glutamate–cysteine ligase regulatory subunit (GCLM), heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1) in APAP-treated mice. The present study revealed that DOP treatment exerted potentially hepatoprotective effects against APAP-induced liver injury. Further investigation about mechanisms indicated that DOP exerted the hepatoprotective effect by suppressing the oxidative stress and activating the Nrf2−Keap1 signaling pathway.

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Cpt1a promoted ROS-induced oxidative stress and inflammation in liver injury via the Nrf2/HO-1 and NLRP3 inflammasome signaling pathway

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2020-0165 ◽

2020 ◽

Author(s):

Xigang Luo ◽

Dapeng Sun ◽

Yinxiang Wang ◽

Fengxiang Zhang ◽

Yi Wang

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Signaling Pathway ◽

Nlrp3 Inflammasome ◽

Receptor Protein ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Over Expression ◽

Vitro Model

Various liver diseases caused by liver damage seriously affect people’s health. The purpose of this study was to clarify that the effects and mechanism of Carnitine palmitoyltransferase 1 (Cpt1a) on oxidative stress and inflammation in liver injury. It was found that the expression of Cpt1a mRNA was up-regulated in model mice of liver injury. So, over-expression of Cpt1a increased reactive oxygen species (ROS) production and malondialdehyde (MDA) levels, and reduced superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-px) levels in vitro model of liver injury. It was also shown that over-expression of Cpt1a suppressed the Nuclear factor-erythroid-2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) signaling pathway. In summary, these data indicate that Cpt1a promotes ROS-induced oxidative stress in liver injury via the Nrf2/HO-1 and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome signaling pathway.

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Salvianolic Acid C against Acetaminophen-Induced Acute Liver Injury by Attenuating Inflammation, Oxidative Stress, and Apoptosis through Inhibition of the Keap1/Nrf2/HO-1 Signaling

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/9056845 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 10

Author(s):

Chien-Ta Wu ◽

Jeng-Shyan Deng ◽

Wen-Chin Huang ◽

Po-Chou Shieh ◽

Mei-Ing Chung ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Liver Failure ◽

Acute Liver Failure ◽

Heme Oxygenase 1 ◽

Molecular Evidence ◽

Related Factor ◽

Drug Induced ◽

Mitochondrial Oxidative Stress ◽

Salvianolic Acid

Acetaminophen (APAP) overdose is one of the most common causes of drug-induced acute liver failure in humans. To investigate the hepatoprotective effect of salvianolic acid C (SAC) on APAP-induced hepatic damage, SAC was administered by daily intraperitoneal (i.p.) injection for 6 days before the APAP administration in mice. SAC prevented the elevation of serum biochemical parameters and lipid profile including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), and triacylglycerol (TG) against acute liver failure. Additionally, SAC reduced the content of malondialdehyde (MDA), the cytochrome P450 2E1 (CYP2E1), and the histopathological alterations and inhibited the production of proinflammatory cytokines in APAP-induced hepatotoxicity. Importantly, SAC effectively diminished APAP-induced liver injury by inhibiting nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR4), and mitogen-activated protein kinases (MAPKs) activation signaling pathway. Moreover, SAC enhanced the levels of hepatic activities of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, and Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in APAP-induced mice. SAC mainly inhibited the activation of apoptotic pathways by reduction of cytochrome c, Bax, and caspase-3 protein expression. Taken together, we provide the molecular evidence that SAC protected the hepatocytes from APAP-induced damage by mitigating mitochondrial oxidative stress, inflammatory response, and caspase-mediated antiapoptotic effect through inhibition of the Keap1/Nrf2/HO-1 signaling axis.

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Galangin Activates Nrf2 Signaling and Attenuates Oxidative Damage, Inflammation, and Apoptosis in a Rat Model of Cyclophosphamide-Induced Hepatotoxicity

Biomolecules ◽

10.3390/biom9080346 ◽

2019 ◽

Vol 9 (8) ◽

pp. 346 ◽

Cited By ~ 28

Author(s):

Aladaileh ◽

Abukhalil ◽

Saghir ◽

Hanieh ◽

Alfwuaires ◽

...

Keyword(s):

Nitric Oxide ◽

Dna Damage ◽

Liver Injury ◽

Oxidative Damage ◽

Biological Activities ◽

B Cell Lymphoma ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Quinone Acceptor

Cyclophosphamide (CP) is a widely used chemotherapeutic agent; however, its clinical application is limited because of its multi-organ toxicity. Galangin (Gal) is a bioactive flavonoid with promising biological activities. This study investigated the hepatoprotective effect of Gal in CP-induced rats. Rats received Gal (15, 30 and 60 mg/kg/day) for 15 days followed by a single dose of CP at day 16. Cyclophosphamide triggered liver injury characterized by elevated serum transaminases, alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and histopathological manifestations. Increased hepatic reactive oxygen species, malondialdehyde, nitric oxide, and oxidative DNA damage along with declined glutathione and antioxidant enzymes were demonstrated in CP-administered rats. CP provoked hepatic nuclear factor-kappaB (NF-κB) phosphorylation and increased mRNA abundance of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) both expression and serum levels. Gal prevented CP-induced liver injury, boosted antioxidants and suppressed oxidative stress, DNA damage, NF-κB phosphorylation and pro-inflammatory mediators. Gal diminished Bax and caspase-3, and increased B-cell lymphoma-2 (Bcl-2) in liver of CP-administered rats. In addition, Gal increased peroxisome proliferator-activated receptor gamma (PPARγ) expression and activated hepatic nuclear factor erythroid 2-related factor 2 (Nrf2) signaling showed by the increase in Nrf2, NAD(P)H: quinone acceptor oxidoreductase-1 (NQO-1) and heme oxygenase 1 (HO-1) in CP-administered rats. These findings suggest that Gal prevents CP hepatotoxicity through activation of Nrf2/HO-1 signaling and attenuation of oxidative damage, inflammation and cell death. Therefore, Gal might represent a promising adjuvant therapy to prevent hepatotoxicity in patients on CP treatment.

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Protective role of Salvia miltiorrhiza Polysaccharides on Florfenicol Induced Oxidative and Apoptotic Injury of Liver in Broilers

10.21203/rs.3.rs-501876/v1 ◽

2021 ◽

Author(s):

Xiao Wang ◽

Yuqing Cui ◽

Chao Han ◽

Yumeng Geng ◽

Di Zhang ◽

...

Keyword(s):

Nitric Oxide ◽

Liver Injury ◽

Protein Expression ◽

Liver Tissue ◽

Salvia Miltiorrhiza ◽

Protective Role ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Mrna And Protein Expression ◽

Liver Tissues

Abstract Salvia miltiorrhiza Polysaccharides (SMPs) can alleviate liver injury in mice, but there are few reports on liver injury of broilers, especially the liver injury caused by antibiotics. To explore the hepatoprotective effects of SMPs against florfenicol (FFC) induced broilers liver injury, the broilers were treated with FFC and SMPs. The results showed SMPs could significantly inhibit the decrease of weight gain and the increase of liver index induced by FFC (P < 0.05). SMPs could significantly reduce the contents of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) in serum and the malondialdehyde (MDA), nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in liver tissues (P < 0.05), also significantly increased the content of total protein (TP) in serum and superoxide dismutase (SOD), catalase (CAT) in liver tissues (P < 0.05). QPCR and western bolt results showed that SMPs significantly increased the mRNA and protein expression of cytochrome P4501A1 (CYP1A1), cytochrome P4502H1 (CYP2H1), nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone-1 (NQO-1) in liver tissue, also significantly reduced the rate of hepatocyte apoptosis and the mRNA and protein expression of p53, cytochrome-C (CytC), caspase-3 in liver tissue (P < 0.05). The results demonstrated that SMPs can inhibit the oxidative stress in hepatocytes by regulating the related proteins in Nrf2 pathway, thereby reducing the apoptosis of hepatocytes, and protecting liver injury.

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Exposure to Salinity and Light Spectra Regulates Glucosinolates, Phenolics, and Antioxidant Capacity of Brassica carinata L. Microgreens

Antioxidants ◽

10.3390/antiox10081183 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1183

Author(s):

Sylvia Maina ◽

Da Hye Ryu ◽

Jwa Yeong Cho ◽

Da Seul Jung ◽

Jai-Eok Park ◽

...

Keyword(s):

Oxidative Stress ◽

High Performance ◽

Antioxidant Activities ◽

Light Exposure ◽

Brassica Carinata ◽

Bioactive Metabolites ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Light Emitting ◽

Flight Mass Spectrometry

The effect of salt treatment on Brassica carinata (BC) microgreens grown under different light wavelengths on glucosinolates (GLs) and phenolic compounds were evaluated. Quantifiable GLs were identified using ultra-high performance-quadrupole time of flight mass spectrometry. Extracts’ ability to activate antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)) was evaluated on human colorectal carcinoma cells (HCT116). Furthermore, BC compounds’ ability to activate expression of nuclear transcription factor-erythroid 2 related factor (Nrf2) and heme-oxygenase-1 (HO-1) proteins was examined using specific antibodies on HCT116 cells. Sinigrin (SIN) was the abundant GLs of the six compounds identified and its content together with total aliphatic GLs increased in saline conditions. Fluorescent (FL) and blue plus red (B1R1) lights were identified as stable cultivation conditions for microgreens, promoting biomass and glucobrassicin contents, whereas other identified individual and total indole GLs behaved differently in saline and non-saline environments. Blue light-emitting diodes and FL light in saline treatments mostly enhanced SIN, phenolics and antioxidant activities. The increased SOD and CAT activities render the BC microgreens suitable for lowering oxidative stress. Additionally, activation of Nrf2, and HO-1 protein expression by the GLs rich extracts, demonstrate their potential to treat and prevent oxidative stress and inflammatory disorders. Therefore, effective salt treatments and light exposure to BC microgreens present an opportunity for targeted regulation of growth and accumulation of bioactive metabolites.

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Ethanol-induced gastric ulcer in rats and intervention of tert-butylhydroquinone: Involvement of Nrf2/HO-1 signalling pathway

Human & Experimental Toxicology ◽

10.1177/0960327119895559 ◽

2019 ◽

Vol 39 (4) ◽

pp. 547-562 ◽

Cited By ~ 4

Author(s):

Z Rahman ◽

DK Dwivedi ◽

GB Jena

Keyword(s):

Gastric Ulcer ◽

Physiological Stress ◽

Mucosal Damage ◽

Gastric Mucosal Damage ◽

Health Concern ◽

Related Factor ◽

Gastric Mucosal Lesion ◽

Nuclear Factor ◽

Standard Drug ◽

Anti Inflammatory

Gastric ulcer (GU) is the most common health concern that occurs due to alcohol consumption, smoking and physiological stress. Ethanol-induced GU in animal model resembles the pathophysiology of human ulcer. The present study was designed to investigate the cytoprotective and anti-inflammatory properties of tert-butylhydroquinone (tBHQ), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, against gastric mucosal damage induced by acute exposure of ethanol (5 ml/kg). The intervention of tBHQ (25 and 50 mg/kg, per os (po)) and omeprazole (20 mg/kg, po) was done for 10 consecutive days. Omeprazole was chosen as a standard drug because it is prescribed for the treatment of GU. Pretreatment of tBHQ decreased gastric mucosal lesion, ulcer index, apoptotic cells and lipid peroxidation level induced by ethanol. Furthermore, the intervention of tBHQ increased gastric mucosa integrity, pH, reduced glutathione, collagen and mucus-producing goblet cells. Intervention of tBHQ increased the expression of antioxidant markers such as Nrf2, haeme oxygenase-1 and catalase and decreased the expressions of inflammatory markers such as nuclear factor kappa-light-chain-enhancer of activated B cells and cyclooxygenase-2. The cytoprotective potential of tBHQ against gastric mucosal damage might be due to its ability to enhance cellular antioxidants and anti-inflammatory responses.

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UJI AKTIVITAS ANTIULCER AIR ALKALI TERIONISASI PADA MENCIT PUTIH JANTAN (MUS MUSCULUS)

JUPE : Jurnal Pendidikan Mandala ◽

10.36312/jupe.v6i1.2275 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Adriyan Suhada ◽

Bq. Fitria Maharani ◽

Ni Komang Wijiani Yanti ◽

Nur'aini Nur'aini

Keyword(s):

Mus Musculus ◽

Mucosal Damage ◽

Positive Control ◽

Negative Control ◽

Gastric Mucosal Damage ◽

Group Vi ◽

Alkaline Water ◽

Water Group ◽

Group I ◽

Water Ph

Alkaline water is water that has antioxidant content and has a structure that is rich in active hydrogen that can cure stomach ulcers. The purpose of this study was to determine the effectiveness of ionized alkaline water as an antiulcers in male white mice (mus musculus). Method of induction of gastric ulcer using aspirin, used as many as 24 male mice (mus musculus) aged 2-3 months used as mice test animals divided into 6 groups each group consisting of 3 animals all groups were given ulcer treatment for 7 days, then group I (negative control) were given aquadest group II (positive control) were given sucralfate, group III were given ph 8 alkaline water group IV was given ph 9.0 alkaline water, group V was given ph 9.5 alkaline water, and group VI was given alkaline water pH 11.5 treatment of each group for the next 7 days on the 14th day the mice were dissected and the gastric mucosa structure was observed and the mucosal damage value was determined. The results showed that alkaline water 9.5 and 11.5 had lower mucosal damage values than negative controls. It can be concluded that the alkaline water ph 9.5 and 11.5 are said to be effective in reducing gastric mucosal damage compared to the negative group given aquadest.

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Dendrobium officinale Flower Extraction Mitigates Alcohol-Induced Liver Injury in Mice: Role of Antisteatosis, Antioxidative, and Anti-Inflammatory

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/1421853 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Yu-Lin Wu ◽

Si-Han Huang ◽

Chun-Mei He ◽

Bo Qiu ◽

Jing-Jing Liu ◽

...

Keyword(s):

Liver Injury ◽

Protective Effect ◽

Serum Levels ◽

Dendrobium Officinale ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Nuclear Factor ◽

Quinone Oxidoreductase ◽

Inflammatory Infiltration ◽

Anti Inflammatory

The study aimed to evaluate the protective effect of Dendrobium officinale flower extraction (DOFE) on alcohol-induced liver injury and its probable mechanisms in mice. The chemical composition of DOFE was performed via UPLC/MS. Male Kunming mice were used to establish alcohol-induced liver injury models by oral gavage of 56% alcohol. Results showed that DOFE dramatically attenuated the increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triacylglycerol (TG). Meanwhile, hematoxylin and eosin and Oil Red O staining showed that DOFE attenuated degeneration, inflammatory infiltration, and lipid droplet accumulation. DOFE was also found to suppress the activity of malonaldehyde (MDA) and enhanced the level of glutathione (GSH) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the liver. The protection of DOFE against oxidative stress was associated with the downregulation of hepatic cytochrome P450 2E1 (CYP2E1) and upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H quinone oxidoreductase l (NQO1). Additionally, DOFE suppressed inflammation via downregulating Toll-like receptor-4 (TLR-4) and nuclear factor kappa-B P65 (NF-κB P65). Thus, DOFE exhibited a significant protective effect against alcohol-induced liver injury through its antisteatosis, antioxidative, and anti-inflammatory effect.

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