Oxidative Stress-mediated Liver Injury Research Articles

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

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.

Riboflavin Bioenriched Soymilk Alleviates Oxidative Stress Mediated Liver Injury, Intestinal Inflammation, and Gut Microbiota Modification in B2 Depletion-Repletion Mice.

Epidemiological evidence emphasizes that ariboflavinosis can lead to oxidative stress, which in turn may mediate the initiation and progression of liver injury and intestinal inflammation. Although vitamin B2 has gained worldwide attention for its antioxidant defense, the relationship between B2 status, oxidative stress, inflammatory response, and intestinal homeostasis remains indistinct. Herein, we developed a B2 depletion-repletion BALB/c mice model to investigate the ameliorative effects of B2 bioenriched fermented soymilk (B2FS) on ariboflavinosis, accompanied by oxidative stress, inflammation, and gut microbiota modulation in response to B2 deficiency. In vivo results revealed that the phenotypic ariboflavinosis symptoms, growth rate, EGRAC status, and hepatic function reverted to normal after B2FS supplementation. B2FS significantly elevated CAT, SOD, T-AOC, and compromised MDA levels in the serum, simultaneously up-regulated Nrf2, CAT, and SOD2, and down-regulated Keap1 gene in the colon. The histopathological characteristics revealed significant alleviation in the liver and intestinal inflammation, confirmed by the downregulation of inflammatory (IL-1β and IL-6) and nuclear transcription (NF-κB) factors after B2FS supplementation. B2FS also increased the abundance and diversity of gut microbiota, increased the relative abundance of Prevotella and Absiella, as well as decreased Proteobacteria, Fusobacteria, Synergistetes, and Cyanobacteria in strong conjunction with antioxidant, anti-inflammatory properties, and gut homeostasis along with the remarkable increase in cecal SCFAs content. We hereby reveal that B2FS can effectively alleviate deleterious ariboflavinosis associated with oxidative stress mediated liver injury, chronic intestinal inflammation, and gut dysbiosis in the B2 depletion-repletion mice model via activation of the Nrf2 signaling pathway.

The protective effect of Veronica ciliata Fisch. Extracts on relieving oxidative stress-induced liver injury via activating AMPK/p62/Nrf2 pathway

Ethnopharmacological relevanceVeronica ciliata Fisch. existed in various Tibetan medicine prescriptions, which was recorded to treat liver diseases in the Tibetan medicine roll of Chinese materia medica. Hypothesis/purposeThe current study aimed to examine the effect of active constituents from V.ciliata relieving oxidative stress-mediated liver injury and clarify the underlying mechanism. Materials and methodstert-Butyl hydroperoxide (BHP) induced liver injury in mice model was established to evaluate the hepatoprotective effect of ethyl acetate extract of V. ciliata (EAFVC). Serum and liver indicators, as well as the histopathological change of liver were examined. Next, the constituents of EAFVC were separated and characterized by high-speed countercurrent chromatography (HSCCC) and Ultra performance liquid chromatography-mass spectrometer (UPLC-MS), respectively. Based on the above, the antioxidant activity of EAFVC and two fractions was evaluated using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2, 2'-azino-bis (3-ethylbenzothiazoli- ne-6-sulfonic acid) (ABTS) free radical scavenging assays. The hepatoprotective activity of EAFVC and its fractions/compounds attenuating ethanol-induced hepatocyte damage in BRL-3A cells was evaluated using the MTT method. The effect of the fraction and compounds with the strongest protective activity on ethanol-induced cytotoxicity, reactive oxygen species (ROS) accumulation, and glutathione (GSH) depletion was investigated. mRNA expression of nuclear factor-E2-related factor 2 (Nrf2) and nuclear factor of κB (NF-κB), as well as their downstream target genes, was determined by RT-qPCR. Finally, the potential mechanism of fraction 1 and luteolin on the AMPK/p62/Nrf2 signal pathway was studied using western blotting. ResultsFirstly, EAFVC could relieve liver impairment induced by t-BHP in mice. Next, fraction 1 enriched with polyphenolic compounds and luteolin derived from EAFVC were screened to yield the highest hepatoprotective activity against ethanol-induced hepatocyte damage. Further study demonstrated that fraction 1 and luteolin relieved BRL-3A cells damage by decreasing the aspartate aminotransferase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) activities, ROS accumulation, as well as the depletion of GSH. Also, we determined that fraction 1 and luteolin suppressed inflammation and apoptosis of BRL-3A cells. The mechanistic studies indicated that fraction 1 could attenuate oxidative stress, inflammation, and apoptosis by activating AMPK phosphorylation, which promotes autophagy associated protein expression (LC3-B, Beclin1 and p62) as well as promote phosphorylation of p62 -dependent autophagic degradation of Keap1, to induce Nrf2 dissociation from Keap1 and translocate to nuclear. Nrf2 in the nuclear activate cytoprotective related genes to exert hepatoprotective function. Finally, we found that luteolin activated the protein expression of p-AMPK, p-p62, p62, Nrf2, and its downstream target genes. ConclusionsThis study clarified that fraction 1 enriched phenolic compounds could attenuate ethanol-induced liver injury in BRL-3A cells via activating AMPK/p62/Nrf2 pathway. Luteolin could serve as the major bioactive component in the therapeutic effect of fraction 1. These active constituents in V. ciliata could be used as the potential drugs targeted activation of AMPK or p62 for relieving oxidative stress-mediated liver disorders.

Trehalose alleviates oxidative stress-mediated liver injury and Mallor-Denk body formation via activating autophagy in mice.

Autophagy is a degradation pathway for long-lived cytoplasmic proteins or damaged organelles and also for many aggregate-prone and disease-causing proteins. Endoplasmic reticulum (ER) stress and oxidative stress are associated with the pathophysiology of various liver diseases. These stresses induce the accumulation of abnormal proteins, Mallory-Denk body (MDB) formation and apoptosis in hepatocytes. A disaccharide trehalose had been reported to induce autophagy and decrease aggregate-prone proteins and cytotoxicity in neurodegenerative disease models. But the effects of trehalose in hepatocytes have not been fully understood. We examined the effect of trehalose on autophagy, ER stress and oxidative stress-mediated cytotoxicity and MDB formation in hepatocytes using mice model with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) treatment for 3months. We administered trehalose by intraperitoneal injection of water containing 10% trehalose (0.02mg/g body weight) every other day for 3months. Our results demonstrated that trehalose induced autophagy and reduced ER stress, oxidative stress, MDB formation and apoptosis in hepatocytes of DDC-fed mice by Western blotting and immunostaining analyses. Electron microscopy revealed that trehalose induced autolysosome formation, which located is close to the MDBs. Thus, our findings suggest that trehalose can become a therapeutic agent for oxidative stress-related liver diseases via activating autophagy.

5-Caffeoylquinic acid ameliorates oxidative stress-mediated cell death via Nrf2 activation in hepatocytes

Context 5-Caffeoylquinic acid (5-CQA) is one of the most abundant compounds found in natural foods including coffee. Objective We investigated whether 5-CQA had a cytoprotective effect through the NF-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) signalling pathway. Materials and methods Nrf2 activation in response to 5-CQA treatment at the concentration of 10–100 μM is evaluated by Western blotting of Nrf2 and ARE reporter gene assay as well as its target gene expression in HepG2 cells. Intracellular reactive oxygen species (ROS) and glutathione (GSH) levels were measured in the tert-butyl hydroperoxide-induced hepatocytes to examined cytoprotective effect of 5-CQA (10–100 μM). The specific role of 5-CQA on Nrf2 activation was examined using Nrf2 knockout cells or Nrf2 specific inhibitor, ML-385. Results Nuclear translocation of Nrf2 is increased by 5-CQA in HepG2 cells which peaked at 6 h. Consequently, 5-CQA significantly increases the ARE reporter gene activity and downstream antioxidant proteins, including glutamate cysteine ligase (GCL), hemeoxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1, and Sestrin2. Nrf2 deficiency or inhibition completely antagonized ability of 5-CQA to induce HO-1 and GCL expression. Cells pre-treated with 5-CQA were rescued from tert-butyl hydroperoxide-induced ROS production and GSH depletion. Nrf2 activation by 5-CQA was due to increased phosphorylation of MAPKs, AMPK and PKCδ. Discussion and conclusions Taken together, our results demonstrate that as a novel Nrf2 activator, 5-CQA, may be a promising candidate against oxidative stress-mediated liver injury. Additional efforts are needed to assess 5-CQA, as a potential therapeutic in liver diseases in vivo and in humans.

Cudrania Tricuspidata Extract and Its Major Constituents Inhibit Oxidative Stress-Induced Liver Injury.

The fruits, leaves, and roots of Cudrania tricuspidata have been reported to contain large amounts of vitamin B, vitamin C, and flavonoids. They exhibit various physiological activities such as antitumor and anti-inflammatory effects. However, the hepatoprotective effects of C. tricuspidata extracts against oxidative stress-mediated liver injury have not yet been investigated. We thus examined whether C. tricuspidata leaf extracts (CTEs) protect against oxidative stress-mediated liver injury in vitro and in vivo and elucidated the underlying mechanism. The cytoprotective effects of CTE through the NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) activation were presented and measured by biochemical analysis in HepG2 cells. To assess the protective effects of CTE in vivo, mice were administered with CTE (250 and 500 mg/kg; 5 days; p.o.) before a single dose of acetaminophen (APAP) (300 mg/kg; 24 h; i.p.). CTE increased ARE luciferase activity when compared with extracts of other parts of C. tricuspidata. CTE upregulated nuclear translocation of Nrf2 and its target gene expression. In addition, CTE inhibited the generation of reactive oxygen species (ROS) and cell death induced by arachidonic acid (AA) and iron (Fe) treatment in primary hepatocytes or HepG2 cells. The cytoprotective effects of CTE against oxidative stress might be due to kaempferol, the major flavonoid present in CTE. Kaempferol pretreatment blocked AA+Fe-induced ROS production and reversed glutathione depletion, which in turn led to decreased cell death. Furthermore, the protective effects of CTE against liver injury induced by excess APAP in mice or primary hepatocytes were observed. CTE could be a promising therapeutic candidate against oxidative stress-induced liver injury.

Aged Citrus Peel (Chenpi) Prevents Acetaminophen-Induced Hepatotoxicity by Epigenetically Regulating Nrf2 Pathway.

Excessive consumption of analgesic drug acetaminophen (APAP) can cause severe oxidative stress-mediated liver injury. Here, we investigated the protective effect and mechanism of aged citrus peel (Chenpi, CP), a Chinese herb usually used in foods in Asia, against APAP-induced hepatotoxicity. CP water (CP-WE), ethanolic (CP-EE), and water extraction residue ethanolic (CP-WREE) extracts were prepared. We found that CP-WREE contained higher content of bioactive flavonoids, including narirutin, nobiletin, and tangeretin, and more effectively enhanced the Nrf2 pathway in ARE-luciferase reporter gene transfected human HepG2-C8 cells. In mouse AML-12 hepatocytes, CP-WREE minimized APAP-induced damage and lipid peroxidation and increased mRNA and protein expressions of Nrf2 and its downstream defense enzymes (HO-1, NQO1, and UGT1A). CP-WREE also downregulated HDACs and DNMTs, upregulated KDMs, and increased the unmethylated Nrf2 promoter level. Additionally, CP-WREE blocked in vitro DNA methyltransferase activity. Taken together, CP-WREE might attenuate oxidative stress-induced hepatotoxicity through epigenetically regulating Nrf2-mediated cellular defense system.

Sipjeondaebo-tang Alleviates Oxidative Stress-Mediated Liver Injury through Activation of the CaMKK2-AMPK Signaling Pathway.

Sipjeondaebo-tang (SDT) is used frequently as a herbal prescription to treat deficiency syndromes in traditional Korean medicine. We investigated the hepatoprotective effects of SDT against oxidative stress and attempted to clarify the underlying molecular mechanisms. SDT pretreatment reduced arachidonic acid (AA) plus iron-mediated cytotoxicity in a concentration-dependent manner and prevented changes in apoptosis-related protein expression. In addition, SDT pretreatment significantly reduced glutathione depletion, hydrogen peroxide production, and mitochondrial dysfunction via treatment with AA plus iron. SDT increased the phosphorylation of AMP-activated protein kinase (AMPK) in accordance with the phosphorylation of Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2). Experiments using an AMPK chemical inhibitor (Compound C) or CaMKK2 chemical inhibitor (STO-609) suggested that the CaMKK2-AMPK signaling pathway contributes to SDT-mediated protection of mitochondria and cells. Moreover, administration of SDT for 4 consecutive days to mice significantly reduced the alanine aminotransferase and aspartate aminotransferase activities induced by carbon tetrachloride, and the numbers of degenerated hepatocytes, infiltrated inflammatory cells, nitrotyrosine-positive cells, and 4-hydroxynonenal-positive cells in liver tissue. Therefore, SDT protects hepatocytes from oxidative stress via CaMKK2-dependent AMPK activation and has the therapeutic potential to prevent or treat oxidative stress-related liver injury.

Carbon monoxide releasing molecule A-1 attenuates acetaminophen-mediated hepatotoxicity and improves survival of mice by induction of Nrf2 and related genes

Acute liver injury is frequently associated with oxidative stress. Here, we investigated the therapeutic potential of carbon monoxide releasing molecule A-1 (CORM A-1) in oxidative stress-mediated liver injury. Overnight-fasted mice were injected with acetaminophen (APAP; 300 mg/kg; intraperitoneally) and were sacrificed at 4 and 12 h. They showed elevated levels of serum transaminases, depleted hepatic glutathione (GSH) and hepatocyte necrosis. Mice injected with CORM A-1 (20 mg/kg) 1 h after APAP administration, had reduced serum transaminases, preserved hepatic GSH and reduced hepatocyte necrosis. Mice that received a lethal dose of APAP (600 mg/kg), died by 10 h; but those co-treated with CORM A-1 showed a 50% survival. Compared to APAP-treated mice, livers from those co-treated with CORM A-1, had upregulation of Nrf2 and ARE genes (HO-1, GCLM and NQO-1). APAP-treated mice had elevated hepatic mRNA levels of inflammatory genes (Nf-κB, TNF-α, IL1-β and IL-6), an effect blunted in those co-treated with CORM A-1. In tert-butyl hydroperoxide (t-BHP)-treated HepG2 cells, CORM A-1 augmented cell viability, reduced oxidative stress, activated the nuclear factor erythroid 2–related factor 2 (Nrf2) and anti-oxidant response element (ARE) genes. The molecular docking profile of CO in the kelch domain of Keap1 protein suggested that CO released from CORM A-1 mediated Nrf2 activation. Collectively, these data indicate that CORM A-1 reduces oxidative stress by upregulating Nrf2 and related genes, and restoring hepatic GSH, to reduce hepatocyte necrosis and thus minimize liver injury that contributes to an overall improved survival rate.

Liver injury induced in Balb/c mice by PM2.5 exposure and its alleviation by compound essential oils.

Accumulating evidence has suggested a strong link between exposure to air pollution and public health. In particular, inhaled airborne particulate matter <2.5 μm in aerodynamic diameter (PM2.5) can rapidly diffuse from the lungs to the systemic blood circulation and accumulate in the liver. In this study, we used a Balb/c mouse model to investigate liver injury caused by PM2.5 inhalation and the anti-inflammatory and antioxidant effects of compound essential oils (CEOs) in alleviating the extent of this injury. The results of serum biochemical and histopathological analyses showed that PM2.5 exposure induced inflammatory liver injury, meantime CEOs pretreatment attenuated PM2.5-induced liver inflammatory injury. Western blot and qRT-PCR assays showed that PM2.5 increased secretion of cytokines, however CEOs suppressed the production of IL-6 and TNF-α. Furthermore, heme oxygenase-1(HO-1) and superoxide dismutase-1(SOD-1) expression levels showed that PM2.5 could trigger oxidative stress-mediated liver injury, whereas CEOs pretreatment might protect against PM2.5-induced liver injury through regulation of the antioxidant system. Molecular analysis showed that the expression of TLR4, a protein which plays a key role in liver health and injury. Results showed that TLR4 was promoted by PM2.5 but inhibited by CEOs pretreatment in PM2.5-induced inflammatory liver injury. In addition, PM2.5-promoted secretion of cytokines by activating TLR4/MyD88 pathway, whereas CEOs might alleviate this type of liver inflammation inhibiting the activation of TLR4/MyD88 signaling pathway.

Epimedium koreanum Ameliorates Oxidative Stress-Mediated Liver Injury by Activating Nuclear Factor Erythroid 2-Related Factor 2.

Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100[Formula: see text][Formula: see text]g/mL) significantly inhibited AA[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA[Formula: see text][Formula: see text][Formula: see text]iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA[Formula: see text][Formula: see text][Formula: see text]iron via Nrf2 activation. In a CCl4-induced mouse model of liver injury, pretreatment with EKE (300[Formula: see text]mg/kg) for four consecutive days ameliorated CCl4-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.

Sulforaphane protects against acetaminophen-induced hepatotoxicity

Oxidative stress is closely associated with acetaminophen (APAP)-induced toxicity. Heme oxygenase-1 (HO-1), an antioxidant defense enzyme, has been shown to protect against oxidant-induced tissue injury. This study investigated whether sulforaphane (SFN), as a HO-1 inducer, plays a protective role against APAP hepatotoxicity in vitro and in vivo. Pretreatment of primary hepatocyte with SFN induced nuclear factor E2-factor related factor (Nrf2) target gene expression, especially HO-1 mRNA and protein expression, and suppressed APAP-induced glutathione (GSH) depletion and lipid peroxidation, which eventually leads to hepatocyte cell death. A comparable effect was observed in mice treated with APAP. Mice were treated with 300 mg/kg APAP 30 min after SFN (5 mg/kg) administration and were then sacrificed after 6 h. APAP alone caused severe liver injuries as characterized by increased plasma AST and ALT levels, GSH depletion, apoptosis, and 4-hydroxynonenal (4-HNE) formations. This APAP-induced liver damage was significantly attenuated by pretreatment with SFN. Furthermore, while hepatic reactive oxygen species (ROS) levels were increased by APAP exposure, pretreatment with SFN completely blocked ROS formation. These results suggest that SFN plays a protective role against APAP-mediated hepatotoxicity through antioxidant effects mediated by HO-1 induction. SFN has preventive action in oxidative stress-mediated liver injury.

Troxerutin protects against 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47)-induced liver inflammation by attenuating oxidative stress-mediated NAD+-depletion

Emerging evidence indicates that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) induces liver injury through enhanced ROS production and lymphocytic infiltration, which may promote a liver inflammatory response. Antioxidants have been reported to attenuate the cellular toxicity associated with polybrominated diphenyl ethers (PBDEs). In this study, we investigated the effect of troxerutin, a trihydroxyethylated derivative of the natural bioflavonoid rutin, on BDE-47-induced liver inflammation and explored the potential mechanisms underlying this effect. Our results showed that NAD+-depletion was involved in the oxidative stress-mediated liver injury in a BDE-47 treated mouse model, which was confirmed by Vitamin E treatment. Furthermore, our data revealed that troxerutin effectively alleviated liver inflammation by mitigating oxidative stress-mediated NAD+-depletion in BDE-47 treated mice. Consequently, troxerutin remarkably restored SirT1 protein expression and activity in the livers of BDE-47-treated mice. Mechanistically, troxerutin dramatically repressed the nuclear translocation of NF-κB p65 and the acetylation of NF-κB p65 (Lys 310) and Histone H3 (Lys9) to abate the transcription of inflammatory genes in BDE-47-treated mouse livers. These inhibitory effects of troxerutin were markedly blunted by EX527 (SirT1 inhibitor) treatment. This study provides novel mechanistic insights into the toxicity of BDE-47 and indicates that troxerutin might be used in the prevention and therapy of BDE-47-induced hepatotoxicity.

Diallyl trisulfide (DATS) effectively attenuated oxidative stress-mediated liver injury and hepatic mitochondrial dysfunction in acute ethanol-exposed mice

The protective effects of diallyl trisulfide (DATS) on acute ethanol-induced liver injury were investigated. Mice were pretreated with DATS (30 mg/kg bw) for 7 d before being exposed to ethanol (4.8 g/kg bw). The biochemical indices (aspartate amino transferase, AST; alanine amino transferase, ALT; triglyceride, TG) were examined to evaluate the protective effects. Mitochondria were isolated for the mitochondrial permeability transition (MPT), membrane potential (Δ Ψ m) and adenosine nucleotide pool assay. The lipid peroxidation (malondialdehyde, MDA), non-enzymatic antioxidant (glutathione, GSH) and enzymatic antioxidants (superoxide dismutase, SOD; catalase, CAT; glutathione reductase, GR; glutathione peroxidase, GSH-Px) were measured both in the liver homogenate and isolated mitochondria. Acute ethanol exposure resulted in the significant increase of the ALT, AST and TG levels and hepatic mitochondria dysfunction shown as MPT, and the decreases of Δ Ψ m, ATP and energy charge (EC). However, DATS pretreatment dramatically attenuated these adverse effects. Beside this, DATS was found to significantly inhibit the increase of the hepatic and mitochondrial MDA levels, which were decreased by 33.3% ( P < 0.01) and 39.0% ( P < 0.01), respectively. In addition, DATS pretreatment markedly suppressed the ethanol-induced decrease of the hepatic GSH level and increased the mitochondrial GSH level. Moreover, the activities of the hepatic antioxidant enzymes (SOD, CAT, and GR) and the mitochondrial antioxidant enzymes (SOD, GR, and GSH-Px) were significantly boosted. Thus, we concluded that DATS dramatically attenuated acute ethanol-induced liver injury and mitochondrial dysfunction. The increase of the hepatic and mitochondrial GSH levels and the elevation of the antioxidant enzymes activities should account for the preventive effects.