Ethanol-induced Oxidative Stress Research Articles

Effects of PPARα against ethanol-induced oxidative stress in mouse gastric mucosa

Effects of PPARα against ethanol-induced oxidative stress in mouse gastric mucosa

Pine pollen extract alleviates ethanol-induced oxidative stress and apoptosis in HepG2 cells via MAPK signaling.

Pine pollen extract (PPE) has various effects such as antioxidant, hypoglycemic and anti-obesity. However, the anti-ALD mechanism of PPE has rarely been studied. In this study, PPE was prepared and chemical components such as total protein, total sugars, total phenols, total flavonoids and polyphenol composition were determined. The effect of PPE on HepG2 cells after ethanol damage was also measured. HepG2 cells were pre-treated with 200μg/mL and 400μg/mL of PPE for 24h followed by treatment with ethanol for 24h. The results suggested that PPE significantly decreased the production of LDH, ROS and MDA. Meanwhile, the levels of GSH and SOD were also increased. The levels of Nrf2, HO-1 and Keap1 were upregulated after PPE treatment. Additionally, Bax were downregulated and Caspase3 activation was inhibited after PPE treatment. What's more, PPE also attenuated the ethanol-induced phosphorylation levels of MAPK in HepG2 cells. Three major phenols were identified as p-coumaric acid, catechins and caffeic acid. These results suggest that PPE can be effective against ALD by alleviating MAPK pathway-mediated oxidative stress and apoptosis. In conclusion, PPE is a natural product with hepatoprotective potential.

A research of marigold flavonoids from marigold residues

In this paper, marigold flavonoids (MF) extracted from defatted marigold has been deeply investigated about the production technology, composition and content, antioxidant activity in vitro or in vivo, and acute oral toxicity for evaluating the comprehensive utilization possibilities. As result, the content of MF can reach 90 % when it is extracted by acetone/water (9:1, v/v) and after filtered when extracts were concentrated until reaching 20 % of soluble solids. Then, the obtained MF was analyzed and mainly composed of quercetagetin (84.7 %), 6-hydroxykahenol (5.0 %), quercetin (0.86 %) and patuletin (1.44 %). Next, results of in vitro antioxidant activity showed that MF has equivalent antioxidant activity with green tea polyphenols (GTP) and quercetin (Que), and significantly superior than other four antioxidants in hydroxyl radical scavenging ability. Results of in vivo antioxidant activity showed that MF can significantly decreased malondialdehyde (MDA) levels, whereas superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) significantly increased compared with ethanol-induced oxidative stress model in the liver tissues, which showed better antioxidant activity than Que. Finally, the acute toxicity tests in Sprague Dawley (SD) rats and ICR mice demonstrated that MF at a dose of 5000 mg/kg body weight failed to alter any of the parameters studied. Therefore, the LD50 value for MF oral toxicity was considered to be 5000 mg/kg body weight. In summary, MF can be a safe and potential antioxidant based on the experimental data in this paper.

Artabotrys odoratissimus Bark Extract Restores Ethanol Induced Redox Imbalance and Toxicity in Hepatocytes and In Vivo Model.

Alcohol-induced oxidative stress is a key player in the development of liver diseases, and herbal alternatives are important means of ameliorating the hepatotoxic effects. The study aimed to evaluate the hepatoprotective potentiality of Artabotrys odoratissimus, an important medicinal shrub from the family Annonaceae. The phenolic compounds from bark ethanol extract (BEE) were detected using RP-HPLC. The in vitro hepatoprotective activity against ethanol-induced damage was studied in HepG2 cells with cell viability assays, mitochondrial membrane potential (MMP) assay, reactive oxygen species (ROS) assay, double staining assay and western blotting. The in vivo mice model was used to evaluate the alcohol-induced stress with liver function enzymes, lipid profile and histopathology. All the thirteen phenolic compounds detected with HPLC were docked onto protein targets such as aspartate amino transferase (AST), alkaline phosphatase (ALP) and inducible nitric oxide synthase (NO). The RP-HPLC detected the presence of various phenolics including rutin, chlorogenic acid and catechin, amongst others. Co-administration of BEE with ethanol alleviated cell death, ROS and MMP in HepG2 cells compared to the negative control. The extract also modulated the MAP kinase/caspase-3 pathway, thereby showing protective effects in HepG2 cells. Also, pre-treatment for 14days with the extract in the mice model before a single toxic dose (5g/kg body weight) reduced the liver injury by bringing the levels of liver function enzymes, lipid profile and bilirubin to near normal. In silico analysis revealed that rutin showed the best binding affinity with all the target proteins in the study. These results provide evidence that BEE possesses significant hepatoprotective effects against ethanol-induced oxidative stress in hepatic cells and in vivo models, which is further validated with in silico analysis.

Protective effect of Hovenia dulcis Thunb. leaf extracts against ethanol-induced DNA damage in SH-SY5Y cells

Ethnopharmacological relevanceHovenia dulcis Thunb. has been used as a medicinal herb for the treatment of hepatic diseases and alcohol intoxication.Aim of the study: The genotoxic effect and the antigenotoxic potential of ethanolic extract of H. dulcis leaves and its methanolic fraction were evaluated against ethanol-induced damages in SH-SY5Y cells. Materials and methodsThe phytochemical analysis and antioxidant activity of H. dulcis extracts were also assessed. In addition, a systems biology analysis was performed to investigate the molecular pathway of action of the H. dulcis leaves compounds. ResultsThe ethanolic extract and its methanolic fraction presented genotoxicity through comet assay at 0.5 and 0.25 mg/mL. On the other hand, both extracts showed protective action against ethanol at all concentrations. Additionally, an NBT assay was performed and demonstrated an ability of the extracts to reduce superoxide anion formation when SH-SY5Y cells were challenged with ethanol. HPLC analysis indicated the presence of quercitrin, isoquercitrin, and rutin. Further, system biology assays indicated a molecular action pathway, where the compounds from the leaves of H. dulcis, in addition to performing free radical scavenging activity, activate PP2A, and may inhibit the apoptosis pathway activated by ethanol-induced oxidative stress. ConclusionsThis work is important to indicate potential antigenotoxic and antioxidant properties of H. dulcis leaves, and its use can be investigated against DNA damage induced by ethanol.

Impact of Antioxidant rich fractions isolated from moss Fissidens grandiflora on alcohol-induced oxidative stress

The present study is aimed to evaluate the antioxidant and hepatoprotective properties of selected ethanolic fractions of Fissidens grandiflora in ethanol-induced oxidative stress in rats. Initially, ethanolic extract of F. grandiflora was fractionated using column chromatography. The preliminary antioxidant screening of these fractions identified two main bioactive fractions (F3 and F4), which were found to have significant radical scavenging and metal ion chelation properties compared with ascorbic acid. Based on the antioxidant profile, F3 and F4 were evaluated for hepatoprotective activity in ethanol-intoxicated rats. The Wistar rats were grouped (n = 6) and treated with F3 and F4 (100 and 200 mg/kg), ethanol (5 g/kg, 20%w/v) and silymarin (100 mg/kg) orally for 28 days. The outcomes of the study found that chronic administration of ethanol significantly (P < 0.0001) altered the liver parameters and oxidative stress markers (MDA, SOD, and CAT). The co-administration of F4 prominently ameliorated the oxidative stress induced by ethanol compared to F3. Histopathological studies further supported the significant protective action of F4. The present study demonstrates that the F. grandiflora possess significant antioxidant properties by augmenting the magnitude of the antioxidant enzymes SOD and CAT and further reducing MDA levels.

A Mixture of Kaempferol-3-O-sambubioside and Kaempferol-3-O-sophoroside from Malvaviscus arboreus Prevents Ethanol-Induced Gastric Inflammation, Oxidative Stress, and Histologic Changes.

Malvaviscus arboreus is used in traditional Mexican medicine to treat gastrointestinal diseases. Therefore, a mixture of Kaempferol-O-sambubioside and Kaempferol-O-sophoroside (MaSS) isolated from flowers of this species was tested as a preventive treatment on gastric lesions induced with ethanol in rats. MaSS was obtained by chromatographic methods and administered by oral pathway to male Sprague Dawley rats with ethanol-induced gastric lesions. Pretreatment with MaSS at doses of 30, 90, 120, and 180 mg/kg significantly prevents gastric lesions, inhibits the increment in relative stomach weight (%) in gastric IL-6, and also provokes an increment of IL-10 concentration and catalase activity. Finally, MaSS prevented edema in the mucosa and submucosa and diminished microscopic gastric lesions provoked by ethanol.

Microbial diversity associated with Tibetan kefir grains and its protective effects against ethanol-induced oxidative stress in HepG2 cells

Tibetan kefir grains (TKGs) and their products are multi-functional health supplements. This study aimed to explore the diversity of microorganisms in Tibetan kefir grains (TKGs) and the protective effect of isolates on ethanol-treated HepG2 cells. Metagenomic sequencing showed that Lactobacillus Kefiranofaciens was the most abundant bacterial taxon, while Kluyveromyces marxianus was the most abundant fungal taxum in TKGs. Thirteen isolates belonging to the genera Lactobacillus (3), Fructobacillus (1), Lactococcus (1), Pediococcus (1), Acetobacter (3), and Kluyveromyces (4), were obtained by cultivation methods. KEGG pathway analysis revealed that K. marxianus contributed four KEGG pathways related to hepatic disease. LC-MS analysis revealed CFEs are rich sources of peptides amino acids, lipids and amino acids. Cell-free extracts (CFEs) prepared from K. marxianus protected HepG2 cells from ethanol-induced injury. Treatment with CFEs from isolates YG-4 and YK-6 significantly increased cell viability and reduced ethanol cytotoxicity. Also, YG-4 and YK-6 decreased reactive oxygen species, malondialdehyde and alanine aminotransferase, increased superoxide dismutase and catalase, and reduced apoptosis and loss of potential in mitochondria. In addition, CFEs, especially YG-4-derived CFEs, decreased ethanol-induced inflammatory cytokines (IL-6, IL-17 and TNF-α), while YG-4 and YK-6 CFEs upregulated the regulatory cytokine IL-4. Thus, YG-4 had the most significant anti-inflammatory effects by reducing ethanol-induced oxidative stress. These isolates’ properties may provide new avenues to use K. maxianus in alcoholic liver disease.

Rhizophora mucronata Lam. (Mangrove) Bark Extract Reduces Ethanol-Induced Liver Cell Death and Oxidative Stress in Swiss Albino Mice: In Vivo and In Silico Studies.

The bark extract of Rhizophora mucronata (BERM) was recently reported for its prominent in vitro protective effects against liver cell line toxicity caused by various toxicants, including ethanol. Here, we aimed to verify the in vivo hepatoprotective effects of BERM against ethanol intoxication with the prediction of potential targets employing in silico studies. An oral administration of different concentrations (100, 200 and 400 mg/kg body weight) of BERM before high-dose ethanol via intraperitoneal injection was performed in mice. On day 7, liver sections were dissected for histopathological examination. The ethanol intoxication caused liver injury and large areas of necrosis. The pre-BERM administration decreased the ethanol-induced liver damage marker tumor necrosis factor-alpha (TNF-α) expression, reduced hepatotoxicity revealed by nuclear deoxyribonucleic acid (DNA) fragmentation and decreased oxidative stress indicated by malondialdehyde and glutathione contents. Our in silico studies have identified BERM-derived metabolites exhibiting the highest predicted antioxidant and free radical scavenger activities. Molecular docking studies showed that most of the metabolites were predicted to be enzyme inhibitors such as carbonic anhydrase inhibitors, which were reported to stimulate the antioxidant defense system. The metabolites predominantly presented acceptable pharmacokinetics and safety profiles, suggesting them as promising new antioxidant agents. Altogether, the BERM extract exerts antioxidative activities and shows promising hepatoprotective effects against ethanol intoxication. Identification of related bioactive compounds will be of interest for future use at physiological concentrations in ethanol-intoxicated individuals.

Quercetin alleviates ethanol-induced hepatic steatosis in L02 cells by activating TFEB translocation to compensate for inadequate autophagy.

This study aimed to investigate the therapeutic effect of quercetin on ethanol-induced hepatic steatosis in L02 cells and elucidate the potential mechanism. In brief, L02 cells were pretreated with or without ethanol (3%) for 24 h, then treated quercetin (80, 40, 20 μM) for 24 h. The transfection procedure was performed with transcription factor EB (TFEB) small interfering RNA (siRNA TFEB) for 24 h. Our results showed that quercetin autophagic flux in the L02 cells, via upregulating of microtubule associated protein light chain 3B (LC3-II) and lysosome-associated membrane protein 1 (LAMP1), then downregulating of protein sequestosome 1 (SQSTM1/p62). Mechanistically, quercetin activated TFEB nuclear translocation, contributing to lysosomal biogenesis and autophagic activation. Accordingly, the genetic inhibition of TFEB-dependent autophagy decreased ethanol-induced fat accumulation in L02 cells via regulating fatty acid β oxidation and lipid synthesis. Subsequently, quercetin-induced TFEB-dependent autophagic activation was also linked to inhibit oxidative stress via suppressing reactive oxygen species (ROS), enhancing activities of antioxidant enzymes, and promoting nuclear transfer of the nuclear factor E2-related factor 2 (Nrf2) translocation. Thus, we uncovered a novel protective mechanism against ethanol-induced hepatic steatosis and oxidative stress through TFEB-mediated lysosomal biogenesis and discovered insufficient autophagy as a novel previously unappreciated autophagic flux.

Functional Teas from Penthorum chinense Pursh Alleviates Ethanol-Induced Hepatic Oxidative Stress and Autophagy Impairment in Zebrafish via Modulating the AMPK/p62/Nrf2/mTOR Signaling Axis.

Penthorum chinense Pursh (PCP), a medicinal and edible plant, is widely used in many clinical liver diseases. Oxidative stress and autophagy impairment play crucial roles in the pathophysiology of alcoholic liver disease (ALD). Therefore, the aim of this study was to elucidate the mechanism of PCP in attenuating ethanol-induced liver injury. The liver-specific transgenic zebrafish larvae (lfabp: EGFP) at three days post-fertilization (3 dpf) were treated with different concentrations of PCP (100, 50and 25μg/mL) for 48h, aftersoaked in a 350mM ethanol for 32h. Whole-mount oil red O, H&E staining and biochemical kits were used to detect fatty liver function and fat accumulation, western blot (WB) and immunofluorescence were used to determine proteins expression, and RT-qPCR was used to further verify the related gene expression. PCP restored zebrafish liver function. Additionally, PCP (as dose-dependent) blocked the expression of cytochrome P450 2E1 (CYP2E1), the production of intracellular reactive oxygen species (ROS) and alleviated liver fat accumulation and oxidative damage. PCP exerted its hepatoprotective function by downregulating the expression of kelch-like ECH-associated protein 1 (Keap1), up-regulating the expression of nucleus factor-E2-related factor 2 (Nrf2) (transferring to the nucleus), and attenuating systemic oxidative stress. Furthermore, PCP reduced the expression of sequestosome 1 (p62/SQSTM1, p62), Atg13, and Beclin 1, up-regulating autophagy signaling pathway. Taken together, the molecular evidence that PCP protected the ethanol-induced hepatic oxidative stress and autophagy impairment through activating AMPK/p62/Nrf2/mTOR signaling axis.

Benzimidazole Derivatives as New Potential NLRP3 Inflammasome Inhibitors That Provide Neuroprotection in a Rodent Model of Neurodegeneration and Memory Impairment.

ObjectiveThe study investigated the effect of newly synthesized benzimidazole derivatives against ethanol-induced neurodegeneration. According to evidence, ethanol consumption may cause a severe insult to the central nervous system (CNS), resulting in mental retardation, neuronal degeneration, and oxidative stress. Targeting neuroinflammation and oxidative stress may be a useful strategy for preventing ethanol-induced neurodegeneration.MethodologyFirstly, the newly synthesized compounds were subjected to molecular simulation and docking in order to predict ligand binding status. Later, for in vivo observations, adult male Sprague Dawley rats were used for studying behavioral and oxidative stress markers. ELIZA kits were used to analyse tumour necrosis factor-alpha (TNF-), nuclear factor-B (NF-B), interleukin (IL-18), and pyrin domain-containing protein 3 (NLRP3) expression, while Western blotting was used to measure IL-1 and Caspase-1 expression.ResultsOur findings suggested that altered levels of antioxidant enzymes were associated with elevated levels of TNF-α, NF-B, IL-1, IL-18, Caspase-1, and NLRP3 in the ethanol-treated group. Furthermore, ethanol also caused memory impairment in rats, as measured by behavioural tests. Pretreatment using selected benzimidazole significantly increased the combat of the brain against ethanol-induced oxidative stress. The neuroprotective effects of benzimidazole derivatives were promoted by their free radical scavenging activity, augmentation of endogenous antioxidant proteins (GST, GSH), and amelioration of lipid peroxide (LPO) and other pro-inflammatory mediators. Molecular docking and molecular simulation studies further supported our hypothesis that the synthetic compounds Ca and Cb had an excellent binding affinity with proper bond formation with their targets (TNF-α and NLRP3).ConclusionIt is revealed that these benzimidazole derivatives can reduce ethanol-induced neuronal toxicity by regulating the expression of cytokines, antioxidant enzymes, and the inflammatory cascade.

Protective effect of curcumin on zebrafish liver under ethanol-induced oxidative stress

Oxidative stress has an important role in determining severe damage to the liver, including steatosis. Curcumin (CUR) is a natural polyphenol compound with antioxidant potential but its mechanism is still unclear. In this study, 2% ethanol (ETH) was used to establish a liver injury model in Tg (fabp10: Ps Red) transgenic zebrafish with the fluorescent liver. Ethanol-treated zebrafish had an increased vacuole rate at 144 h post-fertilization (hpf), thus confirming the effectiveness of the proposed model in inducing liver damage. However, when ethanol was submitted to co-exposure with curcumin, fluorescence area and signal intensity, as well as vacuole rate, were similar to the levels found in the control group. RNA-seq results showed that ethanol and CUR affected the regulation of catalytic activity and phenylalanine metabolism, biosynthesis of amino acids, and arginine and proline metabolism signaling pathways. QRT-PCR analysis also showed that treatment with CUR led to the downregulation of genes involved in the Nrf2-Keap1 signaling pathway and altered the expression pattern of genes related to glutathione metabolism (gsr, gpx1a, gstp1, gsto1, and idh1a). CUR also induced an increase in GSH content and recovered decreased GSH caused by ethanol exposure. The findings discussed herein indicate that CUR can promote glutathione synthesis, which aided in the recovery from ethanol-induced liver damage in zebrafish larvae.

Moringa oleifera mitigates ethanol-induced oxidative stress, fatty degeneration and hepatic steatosis by promoting Nrf2 in mice

BackgroundMoringa oleifera (M. oleifera) is cultivated throughout the world and it is known by numerous regional names and is consumed as medication for various diseases such as hypertension, diabetes, HIV and is potential source of nutrients and natural antioxidants making it among the most useful trees. MethodsWe evaluated the therapeutic potential of M. oleifera on ethanol-induced fatty liver. The mice were treated with 30% ethanol (EtOH) alone or in combination with different concentration of M. oleifera extracts (100, 200 and 400 mg/kg). We performed biochemical estimation for the serum of important liver damage markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and triglyceride (TG). We performed histopathological analysis from the liver tissues of different mice groups. We also performed ELISA assay, western blotting analysis and SPECT imaging to obtain our results. ResultsThe results for serum (AST, p < 0.0001), (ALT, p < 0.0006) and triglyceride (TG, p < 0.0003) were found to be significantly reduced in all doses of M. oleifera extract treatment groups in comparison with the ethanol group. H&E staining analysis and scoring revealed a significant reduction in lipid droplet accumulation and a significant reduction of liver steatosis (p < 0.0001), lobular inflammation (p < 0.0013), ballooning (p < 0.0004) and immunohistochemistry for TNF-α. M. oleifera also ameliorated ethanol-induced oxidative stress evaluated through MDA (p < 0.0001), H2DCFDA, JC-1 staining and a significant down-regulation of CYP2E1 enzyme (p < 0.0001) in the 200 and 400 mg/kg groups in comparison with EtOH groups. M. oleifera extract also boosted the antioxidant response evaluated through total GSH assay (p < 0.0001) and nuclear translocation of Nrf2. Furthermore, we performed SPECT imaging and evaluated the liver uptake value (LUV) to assess the extent of liver damage. LUV was observed to be lower in the ethanol group, whereas LUV was higher in control and M. olifera treated groups. ConclusionIn summary, from this experiment we conclude that M. oleifera extract has the potential to ameliorate ethanol-induced liver damage.

Gastroprotective effect of an active ingredients group of Lindera reflexa Hemsl. On Ethanol-Induced gastric ulcers in Rats: Involvement of VEGFR2/ERK and TLR-2/Myd88 signaling pathway

Lindera reflexa Hemsl. (LR) has been used for the treatment of gastrointestinal disorders. The present study was carried out to investigate the gastroprotective effect of an active ingredients group of Lindera reflexa Hemsl. (LRG) on ethanol-induced gastric ulcer in rats and its possible mechanisms. The ulcer area was measured, and samples of gastric tissue were taken for histochemical, pathological, and biochemical analyses. Pretreatment with LRG protected the gastric mucosa as seen by reduction the GUI and gastric juice volume, regulated gastric acid secretion. LRG counteracted the ethanol-induced oxidative stress by increasing the levels of depleted SOD and CAT as well as significantly attenuating the lipid peroxidation by reducing the levels of MDA and MPO. LRG also reduced release of inflammatory mediator TNF-α, increased the content of PGE2 and inhibited MTL secretion. Immunofluorescence and Western blot analyses confirmed that the co-localization of TLR-2 and MyD88 protein in the gastric mucosa of LRG-treated rats was significantly lower than that of rats with gastric ulcers. Furthermore, LRG also modulated the expression of Ki-67 antigens. LRG markedly increased the expression of phosphorylated form of extracellular signal-regulated kinaseVEGFR2, ERK1/2, AKT and p38, thereby protecting the gastric mucosa. These findings indicated that the gastroprotective effect of LRG is attributable to its antioxidant, anti-inflammatory, and antisecretory properties. In addition, LRG can ameliorate ethanol-induced gastric ulcers in rats by regulating the VEGFR2/ERK and TLR-2/MyD88 signaling pathways.

Bio-Assay Guided Identification of Antioxidant Fractions from Methanolic Extract of Polyalthia longifolia Seeds and their Hepatoprotective Effects against Ethanol Induced Oxidative Stress

The present study is aimed to evaluate the antioxidant and hepatoprotective properties of selected methanolic fractions of Polyalthia longifolia (Sonn.) Thwaite seeds in ethanol-induced oxidative stress in rats. Initially, methanolic extract of Polyalthia longifolia seeds was fractionated using column chromatography. The preliminary antioxidant screening of these fractions identified two main bioactive fractions (F3 and F5), which were found to have significant radical scavenging and metal ion chelation properties compared with ascorbic acid. Based on the antioxidant profile, F3 and F5 were evaluated for hepatoprotective activity in ethanol-intoxicated rats. The Wistar rats were grouped (n=6) and treated with F3 and F5 (200 and 400 mg/kg), ethanol (5 g/kg, 20 % w/v) and silymarin (100 mg/kg) orally for 28 d. The outcomes of the study found that chronic administration of ethanol significantly (p<0.0001) altered the liver parameters and oxidative stress markers (malondialdehyde, superoxide dismutase and catalase). The co-administration of F5 prominently ameliorated the oxidative stress induced by ethanol compared to F3. Histopathological studies further supported the significant protective action of F5. The present study demonstrates that the Polyalthia longifolia seeds possess significant antioxidant properties by augmenting the magnitude of the antioxidant enzymes superoxide dismutase and catalase and further reducing malondialdehyde levels.

Leonurine Protects Hepatocytes from Ethanol-Induced Oxidative Stress via JAK2-STAT3 Pathway

Leonurine Protects Hepatocytes from Ethanol-Induced Oxidative Stress via JAK2-STAT3 Pathway

Novel functional food from an invasive species Polygonum cuspidatum: safety evaluation, chemical composition, and hepatoprotective effects

Abstract Accidentally, we found that the shoots of Polygonum cuspidatum (SPC) have been consumed for centuries as a traditional vegetable in the Shennongjia region of China. Local residents believe that SPC has biological effects such as antibacterial, anti-aging, and antioxidant. To provide scientific support for the use of SPC as a functional food, SPC was evaluated in terms of safety, chemical composition, and antioxidant activity both in vivo and in vitro. In the first, SPC exhibited no adverse cytotoxic effects or acute toxicity in mice. Then the chemical composition of SPC was determined by ultrahigh performance liquid chromatography–electrospray ioniza­tion–quadrupole time of flight tandem mass spectrometry (UHPLC-ESI-QTOF-MS/MS). Twenty-two compounds were identified from the SPC extracts, including phenolic, flavonoid, stilbene, and anthraquinone. Finally, an acute ethanol-induced oxidative stress model in mice showed hepatoprotective effects. In brief, our study indicated that SPC is a safe, multifunctional food with antioxidant and hepatoprotective activities. Importantly, the consumption of SPC as a functional food provides a novel strategy for the efficient utilization of the invasive plant.

Suppression of colonic oxidative stress caused by chronic ethanol administration and attenuation of ethanol-induced colitis and gut leakiness by oral administration of sesaminol in mice.

Chronic consumption of excess ethanol is one of the major risk factors for colorectal cancer (CRC), and the pathogenesis of ethanol-related CRC (ER-CRC) involves ethanol-induced oxidative-stress and inflammation in the colon and rectum, as well as gut leakiness. In this study, we hypothesised that oral administration of sesaminol, a sesame lignan, lowers the risk of ER-CRC because we found that it is a strong antioxidant with very low prooxidant activity. This hypothesis was examined using a mouse model, in which 2.0% v/v ethanol was administered ad libitum for 2 weeks with or without oral gavage with sesaminol (2.5 mg per day). Oral sesaminol administration suppressed the ethanol-induced colonic lesions and the ethanol-induced elevation of the colonic levels of oxidative stress markers (8-hydroxy-2'-deoxyguanosine, malondialdehyde, and 4-hydroxyalkenals). It consistently suppressed the chronic ethanol-induced expressions of cytochrome P450-2E1 and inducible nitric oxide synthase and upregulated heme oxygenase-1 expression, probably via the nuclear factor erythroid-derived 2-like 2 pathway in the mouse colon. Oral sesaminol administration also suppressed the chronic ethanol-induced elevation of colonic inflammation marker levels, such as those of tumour necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1, probably via the nuclear factor-kappa B pathway. Moreover, it prevented the chronic ethanol-induced gut leakiness by restoring tight junction proteins, giving rise to lower plasma endotoxin levels compared with those of ethanol-administered mice. All of these results suggest that dietary supplementation of sesaminol may lower the risk of ER-CRC by suppressing each of the above-mentioned steps in ER-CRC pathogenesis.

Methylene Blue Protects Against Acute Ethanol-Induced Oxidative Stress and Organ Damage

Ethanol (EtOH) intake is an important global health problem which affects many organs such as the brain, liver and stomach. The aim of the study was to examine the effect of the redox dye methylene blue (MethyB) on oxidative stress and histologic damage to the liver, gastric mucosa, and brain induced high dose ethanol (EtOH). Male rats were treated with EtOH (2 ml/rat, 96%) via intragastric route (for two consecutive days). MethyB (20 or 40 mg/kg, intraperitoneally) was given immediately after EtOH administration. The control group received saline. Rats were euthanized three hours after the last treatment. Brain and liver levels of malondialdehyde (MDA), reduced glutathione (GSH), and paraoxonase-1 (PON-1) as well as brain 5-lipoxygenase (5-LOX) and butyrylcholinesterase (BChE) were determined. Histopathological assessment of brain, liver and gastric damage was done. Results indicated that compared to saline treated animals, EtOH caused significant increase in MDA, along with decreased GSH and PON-1 activity in brain and liver. Additionally, it significantly increased 5-LOX and decreased brain BChE activity. The EtOH group showed the presence of dead and red neurons, and damage of glial cells. The liver exhibited vacuolar degeneration, apoptotic hepatocytes and foci of necrosis. The gastric mucosa showed areas of tissue damage, mucosal atrophy, and loss of normal architecture of glandular cells. The EtOH induced biochemical and histopathological alterations were alleviated after treatment with MethyB at a dose-dependent manner. These results demonstrate that MethyB is able to protect against from acute effects of EtOH on brain, liver and gastric tissue via an antioxidant action. MethyB might be of value in reducing tissue injury in acute EtOH intoxication.