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18 pages, 10520 KiB

Open AccessArticle

The Coumarin-Derivative Esculetin Protects against Lipotoxicity in Primary Rat Hepatocytes via Attenuating JNK-Mediated Oxidative Stress and Attenuates Free Fatty Acid-Induced Lipid Accumulation

by Mengmeng Xia, Zongmei Wu, Junyu Wang, Manon Buist-Homan and Han Moshage

Antioxidants 2023, 12(11), 1922; https://doi.org/10.3390/antiox12111922 - 27 Oct 2023

Cited by 3 | Viewed by 1330

Abstract

Coumarin derivates have been proposed as a potential treatment for metabolic-dysfunction-associated fatty liver disease (MAFLD). However, the mechanisms underlying their beneficial effects remain unclear. In the present study, we explored the potential of the coumarin derivate esculetin in MAFLD, focusing on hepatocyte lipotoxicity [...] Read more.

Coumarin derivates have been proposed as a potential treatment for metabolic-dysfunction-associated fatty liver disease (MAFLD). However, the mechanisms underlying their beneficial effects remain unclear. In the present study, we explored the potential of the coumarin derivate esculetin in MAFLD, focusing on hepatocyte lipotoxicity and lipid accumulation. Primary cultures of rat hepatocytes were exposed to palmitic acid (PA) and palmitic acid plus oleic acid (OA/PA) as models of lipotoxicity and lipid accumulation, respectively. Esculetin significantly reduced oxidative stress in PA-treated hepatocytes, as shown by decreased total reactive oxygen species (ROS) and mitochondrial superoxide production and elevated expression of antioxidant genes, including Nrf2 and Gpx1. In addition, esculetin protects against PA-induced necrosis. Esculetin also improved lipid metabolism in primary hepatocytes exposed to nonlipotoxic OA/PA by decreasing the expression of the lipogenesis-related gene Srebp1c and increasing the expression of the fatty acid β-oxidation-related gene Ppar-α. Moreover, esculetin attenuated lipid accumulation in OA/PA-treated hepatocytes. The protective effects of esculetin against lipotoxicity and lipid accumulation were shown to be dependent on the inhibition of JNK and the activation of AMPK, respectively. We conclude that esculetin is a promising compound to target lipotoxicity and lipid accumulation in the treatment of MAFLD. Full article

(This article belongs to the Special Issue Antioxidants in the Protection of Liver Injuries)

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16 pages, 2183 KiB

Open AccessArticle

Combination of Cysteine and Glutathione Prevents Ethanol-Induced Hangover and Liver Damage by Modulation of Nrf2 Signaling in HepG2 Cells and Mice

by Hyeongyeong Kim, Hyung Joo Suh, Ki-Bae Hong, Eun-Jin Jung and Yejin Ahn

Antioxidants 2023, 12(10), 1885; https://doi.org/10.3390/antiox12101885 - 20 Oct 2023

Viewed by 1482

Abstract

Excessive alcohol consumption increases oxidative stress, leading to alcoholic liver disease. In this study, the protective effects of a mixture of cysteine and glutathione against ethanol-induced hangover and liver damage were evaluated in mice and HepG2 cells. Ethanol (2 mL/kg) was orally administered [...] Read more.

Excessive alcohol consumption increases oxidative stress, leading to alcoholic liver disease. In this study, the protective effects of a mixture of cysteine and glutathione against ethanol-induced hangover and liver damage were evaluated in mice and HepG2 cells. Ethanol (2 mL/kg) was orally administered to the mice 30 min before receiving the test compounds (200 mg/kg), and the behavioral and oxidative stress-related biochemical parameters altered by ethanol were analyzed. Acute ethanol administration increased anxiety behavior and decreased balance coordination in mice (p < 0.001); however, a mixture of cysteine and glutathione (MIX) in a 3:1 ratio improved alcohol-induced behavior more effectively than the individual compounds (p < 0.001). The MIX group showed higher ethanol-metabolizing enzyme activity than the control group (p < 0.001) and significantly suppressed the elevation of serum alcohol (p < 0.01) and acetaldehyde (p < 0.001) levels after 1 h of ethanol administration. In HepG2 cells, 2.5 mM MIX accelerated ethanol metabolism and reduced cytochrome P450 2E1 mRNA expression (p < 0.001). MIX also increased the expression of antioxidant enzymes through the upregulation of nuclear erythroid 2-related factor 2 (Nrf2) signaling and consequently suppressed the overproduction of reactive oxygen species and malondialdehyde (p < 0.001). Collectively, MIX alleviates the hangover symptoms and attenuates the alcohol-induced oxidative stress by regulating the Nrf2 pathway. Full article

(This article belongs to the Special Issue Antioxidants in the Protection of Liver Injuries)

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16 pages, 3703 KiB

Open AccessArticle

Selenomethionine Attenuated H₂O₂-Induced Oxidative Stress and Apoptosis by Nrf2 in Chicken Liver Cells

by Lingyu Xie, Yibin Xu, Xiaoqing Ding, Kaixuan Li, Shuang Liang, Danlei Li, Yongxia Wang, Aikun Fu, Weixiang Yu and Xiuan Zhan

Antioxidants 2023, 12(9), 1685; https://doi.org/10.3390/antiox12091685 - 29 Aug 2023

Cited by 4 | Viewed by 1217

Abstract

Earlier studies have shown that selenomethionine (SM) supplements in broiler breeders had higher deposition in eggs, further reduced the mortality of chicken embryos, and exerted a stronger antioxidant ability in offspring than sodium selenite (SS). Since previous studies also confirmed that Se deposition [...] Read more.

Earlier studies have shown that selenomethionine (SM) supplements in broiler breeders had higher deposition in eggs, further reduced the mortality of chicken embryos, and exerted a stronger antioxidant ability in offspring than sodium selenite (SS). Since previous studies also confirmed that Se deposition in eggs was positively correlated with maternal supplementation, this study aimed to directly investigate the antioxidant activities and underlying mechanisms of SS and SM on the chicken hepatocellular carcinoma cell line (LMH). The cytotoxicity results showed that the safe concentration of SM was up to 1000 ng/mL, while SS was 100 ng/mL. In Se treatments, both SS and SM significantly elevated mRNA stability and the protein synthesis rate of glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), two Se-containing antioxidant enzymes. Furthermore, SM exerted protective effects in the H₂O₂-induced oxidant stress model by reducing free radicals (including ROS, MDA, and NO) and elevating the activities of antioxidative enzymes, which performed better than SS. Furthermore, the results showed that cotreatment with SM significantly induced apoptosis induced by H₂O₂ on elevating the content of Bcl-2 and decreasing caspase-3. Moreover, investigations of the mechanism revealed that SM might exert antioxidant effects on H₂O₂-induced LMHs by activating the Nrf2 pathway and enhancing the activities of major antioxidant selenoenzymes downstream. These findings provide evidence for the effectiveness of SM on ameliorating H₂O₂-induced oxidative impairment and suggest SM has the potential to be used in the prevention or adjuvant treatment of oxidative-related impairment in poultry feeds. Full article

(This article belongs to the Special Issue Antioxidants in the Protection of Liver Injuries)

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19 pages, 19512 KiB

Open AccessArticle

A Mixture of Fermented Schizandrae Fructus Pomace and Hoveniae Semen cum Fructus Extracts Synergistically Protects against Oxidative Stress-Mediated Liver Injury

by Jang-Soo Kim, Kyung-Hwan Jegal, Hye-Rim Park, Beom-Rak Choi, Jae-Kwang Kim and Sae-Kwang Ku

Antioxidants 2023, 12(8), 1556; https://doi.org/10.3390/antiox12081556 - 03 Aug 2023

Viewed by 1033

Abstract

Schizandrae Fructus (SF) and Hoveniae Semen cum Fructus (HSCF) have long been used as medicinal herbs for treating various diseases in Asian traditional medicine. In the current study, we investigated the protective effect of fermented SF pomace and HSCF extract 1:1 (w [...] Read more.

Schizandrae Fructus (SF) and Hoveniae Semen cum Fructus (HSCF) have long been used as medicinal herbs for treating various diseases in Asian traditional medicine. In the current study, we investigated the protective effect of fermented SF pomace and HSCF extract 1:1 (w:w) combination mixture (MSH) against carbon tetrachloride (CCl₄)-induced acute liver injury mice. After MSH (50–200 mg/kg) oral administration for 7 consecutive days, animals were injected intraperitoneally with CCl₄ (0.5 mL/kg). Histopathological observation revealed that administration of MSH synergistically decreased the degeneration of hepatocytes and the infiltration of inflammatory cells induced by CCl₄. Moreover, MSH administration reduced the activities of alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase in serum, and mitigated apoptotic cell death in hepatic parenchyma. In addition, MSH alleviated CCl₄-mediated lipid peroxidation by restoring endogenous antioxidants capacities including glutathione contents, superoxide dismutase, and catalase activities. In vitro assessments using tert-butyl hydroperoxide-induced oxidative stress in HepG2 cells revealed that MSH protects hepatocytes by lowering ROS generation and lipid peroxidation via upregulating the transcriptional activity of nuclear factor erythroid-2-related factor 2 and the expression of antioxidant genes. Furthermore, MSH synergistically attenuated the expression of proinflammatory cytokines in CCl₄-injured liver and lipopolysaccharide-stimulated RAW 264.7 cells. Taken together, these findings suggest that MSH has the potential to prevent acute liver damage by effectively suppressing oxidative stress and inflammation. Full article

(This article belongs to the Special Issue Antioxidants in the Protection of Liver Injuries)

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13 pages, 7443 KiB

Open AccessArticle

Hepatic-Modulatory Effects of Chicken Liver Hydrolysate-Based Supplement on Autophagy Regulation against Liver Fibrogenesis

by Yi-Ling Lin, Chih-Ying Chen, Deng-Jye Yang, Yi-Hsieng Samuel Wu, Yue-Jia Lee, Yi-Chou Chen and Yi-Chen Chen

Antioxidants 2023, 12(2), 493; https://doi.org/10.3390/antiox12020493 - 15 Feb 2023

Cited by 2 | Viewed by 1509

Abstract

Chicken-liver hydrolysates (CLHs) have been characterized as performing several biofunctions by our team. This study aimed to investigate if a CLH-based supplement (GBHP01^TM) can ameliorate liver fibrogenesis induced by thioacetamide (TAA) treatment. Our results showed that the TAA treatment caused lower [...] Read more.

Chicken-liver hydrolysates (CLHs) have been characterized as performing several biofunctions by our team. This study aimed to investigate if a CLH-based supplement (GBHP01^TM) can ameliorate liver fibrogenesis induced by thioacetamide (TAA) treatment. Our results showed that the TAA treatment caused lower body weight gains and enlarged livers, as well as higher serum ALT, AST, and ALP levels (p < 0.05). This liver inflammatory and fibrotic evidence was ameliorated (p < 0.05) by supplementing with GBHP01^TM; this partially resulted from its antioxidant abilities, including decreased TBARS values but increased TEAC levels, reduced GSH contents and catalase/GPx activities in the livers of TAA-treated rats (p < 0.05). Additionally, fewer nodules were observed in the appearance of the livers of TAA-treated rats after supplementing with GBHP01^TM. Similarly, supplementing GBHP01^TM decreased fibrotic scars and the fibrotic score in the livers of TAA-treated rats (p < 0.05). Moreover, the increased hepatic IL-6, IL-1β, and TNF-α levels after TAA treatment were also alleviated by supplementing with GBHP01^TM (p < 0.05). Meanwhile, GBHP01^TM could decrease the ratio of LC3B II/LC3B I, but upregulated P62 and Rab7 in the livers of TAA-treated rats (p < 0.05). Taking these results together, the CLH-based supplement (GBHP01^TM) can be characterized as a natural agent against liver fibrogenesis. Full article

(This article belongs to the Special Issue Antioxidants in the Protection of Liver Injuries)

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15 pages, 4914 KiB

Open AccessArticle

Antioxidative and Cytoprotective Efficacy of Ethanolic Extracted Cranberry Pomace against Salmonella Enteritidis Infection in Chicken Liver Cells

by Nada Ahmed, Mohamed El-Fateh, Magdy S. Amer, Reham A. El-Shafei, Muhammad Bilal, Moussa S. Diarra and Xin Zhao

Antioxidants 2023, 12(2), 460; https://doi.org/10.3390/antiox12020460 - 11 Feb 2023

Cited by 2 | Viewed by 1893

Abstract

Salmonella enterica serovar Enteritidis is a globally significant zoonotic foodborne pathogen. Chicken liver is a vital organ that has been recently implicated in several reported human salmonellosis outbreaks in the U.S. One promising strategy for reducing Salmonella in chickens could be through supplementation [...] Read more.

Salmonella enterica serovar Enteritidis is a globally significant zoonotic foodborne pathogen. Chicken liver is a vital organ that has been recently implicated in several reported human salmonellosis outbreaks in the U.S. One promising strategy for reducing Salmonella in chickens could be through supplementation with natural antimicrobial additives. Ethanolic extracted cranberry pomace (CPOH) is an excellent source of bioactive polyphenolic compounds with antioxidant and antimicrobial activities. However, the protective effect of CPOH against S. Enteritidis-induced chicken hepatic cell damage remains unclear. In this study, we used a chicken hepatoma cell (LMH) infection model to investigate the protective effects and potential mechanisms of CPOH. CPOH increased the viability of S. Enteritidis-infected LMH cells. Furthermore, CPOH reduced the adhesion and invasion of S. Enteritidis to LMH cells. CPOH downregulated the expression of Rho GTPase genes that are essential for Salmonella’s entry into LMH cells. Additionally, the expression of antioxidant regulatory genes, such as Nrf2, HO-1, Txn, and Gclc, was increased. Our data show that CPOH effectively protected LMH cells from cell damage through the inhibition of S. Enteritidis adhesion and invasion, as well as the induction of the expression of master antioxidant genes. These findings offer opportunities to develop sustainable, safe, and economic strategies to reduce the colonization and pathogenesis of Salmonella. Full article

(This article belongs to the Special Issue Antioxidants in the Protection of Liver Injuries)

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Review

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26 pages, 1762 KiB

Open AccessReview

The Roles of NFR2-Regulated Oxidative Stress and Mitochondrial Quality Control in Chronic Liver Diseases

by Jeong-Su Park, Nodir Rustamov and Yoon-Seok Roh

Antioxidants 2023, 12(11), 1928; https://doi.org/10.3390/antiox12111928 - 29 Oct 2023

Cited by 2 | Viewed by 1690

Abstract

Chronic liver disease (CLD) affects a significant portion of the global population, leading to a substantial number of deaths each year. Distinct forms like non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (ALD), though they have different etiologies, highlight shared pathologies [...] Read more.

Chronic liver disease (CLD) affects a significant portion of the global population, leading to a substantial number of deaths each year. Distinct forms like non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (ALD), though they have different etiologies, highlight shared pathologies rooted in oxidative stress. Central to liver metabolism, mitochondria are essential for ATP production, gluconeogenesis, fatty acid oxidation, and heme synthesis. However, in diseases like NAFLD, ALD, and liver fibrosis, mitochondrial function is compromised by inflammatory cytokines, hepatotoxins, and metabolic irregularities. This dysfunction, especially electron leakage, exacerbates the production of reactive oxygen species (ROS), augmenting liver damage. Amidst this, nuclear factor erythroid 2-related factor 2 (NRF2) emerges as a cellular protector. It not only counters oxidative stress by regulating antioxidant genes but also maintains mitochondrial health by overseeing autophagy and biogenesis. The synergy between NRF2 modulation and mitochondrial function introduces new therapeutic potentials for CLD, focusing on preserving mitochondrial integrity against oxidative threats. This review delves into the intricate role of oxidative stress in CLD, shedding light on innovative strategies for its prevention and treatment, especially through the modulation of the NRF2 and mitochondrial pathways. Full article

(This article belongs to the Special Issue Antioxidants in the Protection of Liver Injuries)

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15 pages, 806 KiB

Open AccessReview

Preventative and Therapeutic Effects of Astaxanthin on NAFLD

by Nor Hafiza Sayuti, Khairul Najmi Muhammad Nawawi, Jo Aan Goon, Norfilza Mohd Mokhtar, Suzana Makpol and Jen Kit Tan

Antioxidants 2023, 12(8), 1552; https://doi.org/10.3390/antiox12081552 - 03 Aug 2023

Cited by 3 | Viewed by 1995

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a significant public health issue owing to its high incidence and consequences, and its global prevalence is presently 30% and rising, necessitating immediate action. Given the current controversies related to NAFLD, the search for novel therapeutic interventions [...] Read more.

Non-alcoholic fatty liver disease (NAFLD) is a significant public health issue owing to its high incidence and consequences, and its global prevalence is presently 30% and rising, necessitating immediate action. Given the current controversies related to NAFLD, the search for novel therapeutic interventions continues. Astaxanthin is a carotenoid that primarily originates from marine organisms. It is the best antioxidant among carotenoids and one of the most significant components in treating NAFLD. The use of astaxanthin, a xanthophyll carotenoid, as a dietary supplement to treat chronic metabolic diseases is becoming more evident. According to growing data, astaxanthin may be able to prevent or even reverse NAFLD by reducing oxidative stress, inflammation, insulin resistance, lipid metabolism, and fibrosis. Astaxanthin might become a viable therapeutic or treatment option for NAFLD in the upcoming years. Elucidating the impact and mechanism of astaxanthin on NAFLD would not only establish a scientific basis for its clinical application, but also potentially enhance the precision of experimental methodology for future investigations targeting NAFLD treatment. This review explores the potential preventive and therapeutic effects of astaxanthin on liver disorders, especially NAFLD. Full article

(This article belongs to the Special Issue Antioxidants in the Protection of Liver Injuries)

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