A novel strategy for detoxification of deoxynivalenol via modification of both toxic groups.

Deoxynivalenol (DON) is the most abundant mycotoxin in cereal crops and derived foods and is of great concern in agriculture. Bioremediation strategies have long been sought to minimize the impact of mycotoxin contamination, but few direct and effective enzyme-catalyzed detoxification methods are currently available. In this study, we established a multi-enzymatic cascade reaction and successfully achieved detoxification at double sites: glutathionylation for the C-12,13 epoxide group and epimerization for the C-3 hydroxyl group. This yielded novel derivatives of DON, 3-epi-DON-13-glutathione (3-epi-DON-13-GSH) as well as its by-product, 3-keto-DON-13-GSH, for which precise structures were validated via liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS) and nuclear magnetic resonance (NMR) spectroscopy. Both cell viability and DNA synthesis assays demonstrated dramatically decreased cytotoxicity of the double-site modified product 3-epi-DON-13-GSH. These findings provide a promising and urgently needed novel method for addressing the problem of DON contamination in agricultural and industrial settings.

Biochemistry behind firmness retention of jujube fruit by combined treatment of acidic electrolyzed water and high-voltage electrostatic field.

Harvested jujube (Zizyphus jujuba Mill) is prone to softening due to active metabolism. This study investigated the effects of acidic electrolyzed water (AEW), high-voltage electrostatic field (HVEF) and their combination (AEW + HVEF) on softening and associated cell wall degrading enzymes (CWDEs), cell membrane integrity and antioxidant system of 'Huping' jujube during storage at 0 ± 1 °C. The results indicated that fruit subjected to AEW + HVEF, AEW or HVEF treatments maintained firmness 15.7%, 10.7%, and 5.3% higher than that of untreated control fruit at the end of 90 days cool storage. Fruit treated with AEW + HVEF could better maintain cell membrane integrity and exhibit lower activities of CWDEs and higher antioxidant capacity than that treated with either AEW or HVEF. Correlation analysis suggested that inhibition of softening was associated with reduction of CWDEs activities, and maintenance of membrane integrity and antioxidant system.

Investigation of sulfur-containing compounds in spears of green and white Asparagus officinalis through LC-MS and HS-GC-MS.

Asparagus officinalis is largely consumed as food in many parts of the world, and due to its content in secondary metabolites can be considered as a vegetable with health-promoting value. Part of its organoleptic qualities can be ascribed to the presence of sulfur-containing compounds, nevertheless qualitative data about the volatile and non-volatile pools of these compounds in green and white spears of asparagus are poorly investigated. Due to the wide alimentary use of this crop and the potential biological properties of S-containing compounds, research aimed at filling this gap is required. In this paper, a comprehensive characterization of S-metabolites in asparagus performed by LC-MS and GC-MS is reported. Both green and white varieties of asparagus were considered. The fresh vegetal material was subjected to different sample preparation procedures, such as solvent extraction, distillation, and headspace sampling. Furthermore, a derivatization protocol with 4,4'-dithiodipyridine was used for low-molecular weight thiols, and both derivatized and underivatized compounds were analysed by LC-MS. The methods allowed to identify 80 S-containing metabolites in asparagus samples, and to assess the distribution of these compounds in different parts of the spears. Results were discussed comparing the literature, and the identified compounds were considered to explain some peculiar taste and odorous properties of green and white asparagus, although further research is required to confirm our hypotheses. Overall, in this work we report for the first time an exhaustive characterization of S-compounds profile in spears of green and white Asparagus varieties. Furthermore, results indicate that multiple approaches should be used to study the S-containing metabolites of this plant, due to their diverse chemical properties.

The combined treatments of brassinolide and zeaxanthin better alleviate oxidative damage and improve hypocotyl length, biomass, and the quality of radish sprouts stored at low temperature.

The rot and deterioration of sprouts are closely related to their physiological state and postharvest storage quality. The study investigated the influences of brassinolide, zeaxanthin, and their combination on physiological metabolism, chlorophyll fluorescence, and nutritional quality of radish sprouts stored at 4 °C. The combined treatments enhanced hypocotyl length, fresh weight, contents of secondary metabolites, nutritional ingredients, glutathione, the photoprotective capacity of PSII, and FRAP level in radish sprouts compared with zeaxanthin alone. The combined treatments enhanced hypocotyl length, fresh weight, glutathione content, Fv/Fm value, and antioxidant capacity in sprouts compared to brassinolide alone. The combined treatment of zeaxanthin and brassinolide could make radish sprouts keep high biomass and antioxidant capacity by increasing the contents of stress-resistant metabolites and by weakening the photoinhibition of PSII in radish sprouts stored at 4 °C.

Modification of myofibrillar protein gelation under oxidative stress using combined inulin and glutathione.

The effects of inulin (1.5%), glutathione (GSH, 0.05%), and their combination (1.5% inulin + 0.05% GSH) on the conformational structure and gel performance of pork myofibrillar protein (MP) under oxidation condition were examined. The addition of GSH significantly prevented oxidation-induced carbonylation, reduction of α-helix content, and protein aggregation. As a result, treatment with GSH significantly reduced the particle size of oxidized MP by 35%, increased the solubility by 17.3%, and improved the gelling properties. The presence of inulin also obviously enhanced the gelling behavior of MP under oxidation condition, although it could hardly inhibit the modification of MP structure caused by oxidation. Treatment with inulin + GSH exhibited the highest cooking yield (84.2%) and the best textural characteristics, with a denser and more uniform network structure comprising evenly distributed small pores. The findings of this study provide a useful method for processing meat protein gel products with better oxidative stability and textural properties.

Histone demethylase UTX aggravates acetaminophen overdose induced hepatotoxicity through dual mechanisms.

Acetaminophen (APAP) overdose is a major cause of acute liver failure, while the underlying mechanisms of APAP hepatotoxicity are not fully understood. Recently, emerging evidence suggests that epigenetic enzymes play roles in APAP-induced liver injury. Here, we found that Utx (ubiquitously transcribed tetratricopeptide repeat, X chromosome, also known as KDM6A), a X-linked histone demethylase which removes the di- and tri-methyl groups from histone H3K27, was markedly induced in the liver of APAP-overdosed female mice. Hepatic deletion of Utx suppressed APAP overdose-induced hepatotoxicity in female but not male mice. RNA-sequencing analysis suggested that Utx deficiency in female mice upregulated antitoxic phase II conjugating enzymes, including sulfotransferase family 2 A member 1 (Sult2a1), thus reduces the amount of toxic APAP metabolites in injured liver; while Utx deficiency also alleviated ER stress through downregulating transcription of ER stress genes including Atf4, Atf3, and Chop. Mechanistically, Utx promoted transcription of ER stress related genes in a demethylase activity-dependent manner, while repressed Sult2a1 expression through mediating H3K27ac levels independent of its demethylase activity. Moreover, overexpression of Sult2a1 in the liver of female mice rescued APAP-overdose induced liver injury. Together, our results indicated a novel UTX-Sult2a1 axis for the prevention or treatment of APAP-induced liver injury.

The impact of glutathione metabolism in autism spectrum disorder.

This paper reviews the potential role of glutathione (GSH) in autism spectrum disorder (ASD). GSH plays a key role in the detoxification of xenobiotics and maintenance of balance in intracellular redox pathways. Recent data showed that imbalances in the GSH redox system are an important factor in the pathophysiology of ASD. Furthermore, ASD is accompanied by decreased concentrations of reduced GSH in part caused by oxidation of GSH into glutathione disulfide (GSSG). GSSG can react with protein sulfhydryl (SH) groups, thereby causing proteotoxic stress and other abnormalities in SH-containing enzymes in the brain and blood. Moreover, alterations in the GSH metabolism via its effects on redox-independent mechanisms are other processes associated with the pathophysiology of ASD. GSH-related regulation of glutamate receptors such as the N-methyl-D-aspartate receptor can contribute to glutamate excitotoxicity. Synergistic and antagonistic interactions between glutamate and GSH can result in neuronal dysfunction. These interactions can involve transcription factors of the immune pathway, such as activator protein 1 and nuclear factor (NF)-κB, thereby interacting with neuroinflammatory mechanisms, ultimately leading to neuronal damage. Neuronal apoptosis and mitochondrial dysfunction are recently outlined as significant factors linking GSH impairments with the pathophysiology of ASD. Moreover, GSH regulates the methylation of DNA and modulates epigenetics. Existing data support a protective role of the GSH system in ASD development. Future research should focus on the effects of GSH redox signaling in ASD and should explore new therapeutic approaches by targeting the GSH system.

A novel HPLC-MS/MS approach for the identification of biological thiols in vegetables.

Thiols are important natural molecules with diverse functions, ranging from acting as antioxidants that prevent chronic diseases to contributing aromas to foods and beverages. Biological thiols such as glutathione are of particular interest due to their functional roles, which include helping maintain cellular redox homeostasis and detoxifying reactive oxygen species. However, knowledge of thiol metabolism in plants is limited to studying known compounds, whereas other important thiol-containing metabolites could also exist. This work aimed to develop a new analytical approach for screening of thiols in plants, using four vegetal examples and beginning with HPLC-MS/MS in precursor ion scan mode, after extraction and thiol-specific derivatisation with 4,4'-dithiodipyridine (DTDP). Compound identity for prospective thiols was then proposed using HPLC with high resolution MS, and verified with authentic standards. This approach could lead to prospecting studies that identify thiols with potential roles in metabolic pathways, nutritional value of vegetables, or flavouring of foods.

Current etiological comprehension and therapeutic targets of acetaminophen-induced hepatotoxicity.

Acetaminophen (APAP) is the most popular mild analgesic and antipyretic drug used worldwide. APAP overdose leads to drug-induced hepatotoxicity and can cause hepatic failure if treatment delayed. It is adequately comprehended that the metabolism of high-dose APAP by cytochrome P450 enzymes generates N-acetyl-p-benzoquinone imine (NAPQI), a toxic metabolite, which leads to glutathione (GSH) depletion, oxidative stress, and activation of various complex molecular pathways that initiate liver injury and downstream hepatic necrosis. Administration of activated charcoal followed by N-acetylcysteine (NAC) is considered the mainstay therapy; however, including side effects and limitation of rescuing for the delayed patients where liver transplantation may be a lifesaving procedure. Many complex signal transduction pathways such as c-Jun NH2-terminal kinase (JNK), mammalian target of rapamycin (mTOR), nuclear factor (NF)-κB, and NF (erythroid-derived 2)- like 2 (Nrf2) are involved in the development of APAP hepatotoxicity, but yet hasn't been comprehensively studied; thus, the search for effective antidotes and better management strategies continues. Here, we reviewed the most current advances to elucidate the etiological factors and therapeutic targets that could provide better strategies for the management of APAP-induced hepatotoxicity.

Multivariate analysis reveals effect of glutathione-enriched inactive dry yeast on amino acids and volatile components of kiwi wine.

Principal component analysis (PCA) and partial least squares (PLS) regression were applied to investigate the effect of glutathione-enriched inactive dry yeast (g-IDY) on the amino acids and volatile components of kiwi wine. Results indicated that the addition of g-IDY had positive effect on most amino acids of kiwi wine, especially glutamine and glycine. In case of pure juice fermentation, the concentrations of ethyl decanoate, 2-methylbutyric acid, trans-2-nonenal and hexyl butyrate had notably positive correlation with the addition of g-IDY. PLS regression indicated that the amino acids were highly interrelated to the volatile compositions, and glycine had the strongest positive impact on the concentrations of esters and total volatile components. This might explain the similar effect of g-IDY on the amino acids and volatile components of kiwi wine. Besides, PLS regression showed that E-nose was a good method to predict volatile compositions of kiwi wine, especially esters.

Treatment of dilated cardiomyopathy in a mouse model of Friedreich's ataxia using N-acetylcysteine and identification of alterations in microRNA expression that could be involved in its pathogenesis.

Deficient expression of the mitochondrial protein, frataxin, leads to a deadly cardiomyopathy. Our laboratory reported the master regulator of oxidative stress, nuclear factor erythroid 2-related factor-2 (Nrf2), demonstrates marked down-regulation after frataxin deletion in the heart. This was due, in part, to a pronounced increase in Keap1. To assess if this can be therapeutically targeted, cells were incubated with N-acetylcysteine (NAC), or buthionine sulfoximine (BSO), which increases or decreases glutathione (GSH), respectively, or the NRF2-inducer, sulforaphane (SFN). While SFN significantly (p < 0.05) induced NRF2, KEAP1 and BACH1, NAC attenuated SFN-induced NRF2, KEAP1 and BACH1. The down-regulation of KEAP1 by NAC was of interest, as Keap1 is markedly increased in the MCK conditional frataxin knockout (MCK KO) mouse model and this could lead to the decreased Nrf2 levels. Considering this, MCK KO mice were treated with i.p. NAC (500- or 1500-mg/kg, 5 days/week for 5-weeks) and demonstrated slightly less (p > 0.05) body weight loss versus the vehicle-treated KO. However, NAC did not rescue the cardiomyopathy. To additionally examine the dys-regulation of Nrf2 upon frataxin deletion, studies assessed the role of microRNA (miRNA) in this process. In MCK KO mice, miR-144 was up-regulated, which down-regulates Nrf2. Furthermore, miRNA screening in MCK KO mice demonstrated 23 miRNAs from 756 screened were significantly (p < 0.05) altered in KOs versus WT littermates. Of these, miR-21*, miR-34c*, and miR-200c, demonstrated marked alterations, with functional clustering analysis showing they regulate genes linked to cardiac hypertrophy, cardiomyopathy, and oxidative stress, respectively.

Antioxidant activity from inactivated yeast: Expanding knowledge beyond the glutathione-related oxidative stability of wine.

Maintaining wine oxidative stability during barrel ageing and shelf life storage remains a challenge. This study evaluated the antioxidant activities of soluble extracts from seven enological yeast derivatives (YDs) with increased glutathione (GSH) enrichment. YDs enriched in GSH appeared on average 3.3 times more efficient at quenching radical species than YDs not enriched in GSH. The lack of correlation (Spearman correlation ρ = 0.46) between the GSH concentration released from YDs and their radical scavenging activity shed light on other non-GSH compounds present. After 4-methyl-1,2-benzoquinone derivatization, UHPLC-Q-ToF MS analyses specifically identified 52 nucleophiles potentially representing an extensive molecular nucleophilic fingerprint of YDs. The comparative analysis of YD chemical oxidation conditions revealed that the nucleophilic molecular fingerprint of the YD was strongly correlated to its antiradical activity. The proposed strategy shows that nucleophiles co-accumulated with GSH during the enrichment of YDs are responsible for their antioxidant activities.

Bioavailability of coenzyme Q10 loaded in an oleogel formulation for oral therapy: Comparison with a commercial-grade solid formulation.

Coenzyme Q10 (CoQ10) is essential in mitochondrial bioenergetics and is a potent endogenous antioxidant. Low CoQ10 levels are associated with neurodegenerative, metabolic, muscular and cardiovascular disorders. Early treatment with high doses (5-50 mg/kg/day) demonstrated to limit the onset and progression of neuropathology. Recently, we developed an oleogel matrix able to support a high dose of oil-dissolved CoQ10, easy to swallow by CoQ10-deficient patients who suffer from secondary dysphagia. In the present study, we evaluated the bioavailability of oleogel-dissolved CoQ10 and plasma antioxidant status in healthy adults in single-dose and repeated-dose studies. The single-dose study demonstrated that, in terms of CoQ10 bioavailability, 1 g CoQ10/5g oleogel-disk was equivalent to the solid form (1 g CoQ10/three 00-size-capsules), whereas the repeated-dose study (14-days-administration) demonstrated a significantly higher increase in plasma CoQ10 when administered through the oleogel, which could be compatible with the levels necessary to achieve an adequate therapeutic response. Also, a trend to a higher plasma apparent half-life (greater than24 h) was observed for the oleogel-loaded-CoQ10. In conclusion, the oleogel matrix does not compromise the oil-dissolved CoQ10 bioavailability and can prevent the non-adherence to this vital supplementation in patients with high CoQ10 requirements. No significant variation in the plasma antioxidant status (vitamins A, E and C, glutathione and TBARs) was observed.

OSU-A9 induced-reactive oxygen species cause cytotoxicity in duodenal and gastric cancer cells by decreasing phosphorylated nuclear pyruvate kinase M2 protein levels.

Pyruvate kinase M2 (PKM2) is a key enzyme responsible for the final step of glycolysis. It is still unclear whether PKM2 is involved in reactive oxygen species (ROS)-mediated cytotoxicity in gastrointestinal cancer, and what mechanisms are involved. One duodenal (AZ521) and two gastric (NUGC and SCM-1) cancer cell lines were treated with an indole-3-carbinol derivative OSU-A9, which caused cytotoxicity in acute myeloid leukemia through ROS generation. OSU-A9 caused a dose- and time-dependent cytotoxicity and induced apoptosis in duodenal and gastric cancer cells through ROS generation. Pretreatment with ROS scavengers rescued cancer cells from apoptosis and concomitant poly (ADP-ribose) polymerase cleavage, implying a key role of ROS in OSU-A9-induced cell death. Moreover, OSU-A9-induced ROS generation decreased protein levels of pTyr105-PKM2, and this effect was rescued by pretreatment with ROS scavengers. Interestingly, pTyr105-PKM2 protein levels decreased in the cell nucleus rather than in the cytoplasm. PKM2 overexpression partially rescued the survival of duodenal and gastric cancer cells treated with OSU-A9. Furthermore, the anticancer activity of OSU-A9 extended in vivo, as OSU-A9 administered by oral gavage suppressed the growth of AZ521 xenograft tumors in nude mice without obvious toxicity. In conclusion, OSU-A9 inhibited duodenal and gastric cancer cell proliferation through ROS generation and caused a subsequent decrease in nuclear pTyr105-PKM2 protein. These findings provide evidence for the non-canonical activity of PKM2 in cancer cell survival. Furthermore, they highlight the potential role of PKM2 as a future therapeutic target for duodenal and gastric cancer.

Metabolic diversity conveyed by the process leading to glutathione accumulation in inactivated dry yeast: A synthetic media study.

Glutathione-rich inactivated dry yeasts (GSH-IDY) are purported to accumulate glutathione intracellularly and then released into the must. Glutathione is beneficial for wine quality, but research has highlighted that GSH-IDYs have a synergic antioxidant effect similar to that of molecular GSH. Combination of negative mode ultra-high-resolution Fourrier-Transform Ion-Cyclotron-Resonance Mass Spectrometry ((-)FT-ICR-MS), ultra-high-performance liquid chromatography coupled to a Quadrupole-Time of Flight mass spectrometer (UHPLC-Q-ToF-MS) and HPLC/Diode Detector Array (DAD)-Fluorescence spectroscopy was applied to three inactivated dry yeasts soluble fractions, with increasing intracellular glutathione concentration, in order to explore the chemical diversity released in different synthetic media. Using the mean of size exclusion chromatography/DAD and fluorescence detection we report than most of the signals detected were below the 5-75 kDa-calibrated region of the chromatogram, indicating that most of the soluble protein fraction is composed of low molecular weight soluble peptides. In light of these results, high-resolution mass spectrometry was used to scan and annotate the low molecular weight compounds from 50 to 1500 Da and showed that GSH level of enrichment in IDYs was correlated to a discriminant chemical diversity of the corresponding soluble fractions. Our results clearly show an impact of the GSH accumulation process not only visible on the glutathione itself, but also on the global diversity of compounds. Within the 1674 ions detected by (-)FT-ICR-MS, the ratio of annotated elemental formulas containing carbon, hydrogen, oxygen, nitrogen and sulfur (CHONS) to annotated elemental formulas containing carbon, hydrogen, oxygen (CHO) increased from 0.2 to 2.1 with the increasing levels of IDYs GSH content and 36 unique CHONS annotated formulas were unique to the IDY with the highest concentration of GSH. Amongst the 1674 detected ions 193 were annotated as potential peptides (from 2 to 5 residues), 61 ions were annotated as unique amino acid combinations and 46% of which being significantly more intense in GSH-rich IDY. Thus, the process leading to the accumulation of glutathione also involves other metabolic pathways which contribute to an increase in CHONS containing compounds potentially released in wine, notably peptides.

Pigment-depletion in Atlantic salmon (Salmo salar) post-smolt starved at elevated temperature is not influenced by dietary carotenoid type and increasing α-tocopherol level.

Pigment-depletion in the fillets of farmed Atlantic salmon (Salmo salar) arises after periods of elevated water temperatures with voluntary starving. This study tested the effects of dietary pre-loading with different pigment carotenoids (astaxanthin and/or canthaxanthin) combined with two α-tocopherol levels (normal and high: 500 and 1000 mg/kg, respectively) on pigment-depletion in vivo in Atlantic salmon after four weeks of challenge. We also tested whether oxidative stress manifested as an underlying depletion mechanism. Carotenoid levels in whole fillet homogenates were not decreased significantly post-challenge but fillet α-tocopherol concentrations were increased significantly in contrast to decreased oxidative stress indices. However, image analysis revealed localised fillet pigment-depletion following all dietary treatments. These data imply that localised pigment-depletion was not prevented by pre-loading of the fillet with different carotenoid-types/mixtures and increased of α-tocopherol levels from normal to high, respectively. Further, we suggest that oxidative stress might not facilitate pigment-depletion in vivo.

Fatty acid metabolic flux and lipid peroxidation homeostasis maintain the biomembrane stability to improve citrus fruit storage performance.

Little is known about the variations of fresh fruit biomembrane and its physiological and biochemical characteristics during storage. A navel orange mutant 'Gannan No.1' (Citrus sinensis Osbeck) showed higher membrane stability and titratable acid while lower calyx senescence compared with wild-type 'Newhall'. The membrane damage was significantly reduced in 'Gannan No.1' under 10% polyethylene-glycol (41.16% vs. 8.77%) and 30% polyethylene-glycol (52.59% vs.16.11%) treatments on day 45 after harvest. Consistently, membrane electrolyte leakage and malondialdehyde were significantly decreased in 'Gannan No.1', and superoxide dismutase and glutathione reductase were activated. A metabolic analysis was performed to evaluate membrane fatty acid unsaturation and peroxidation. Linolenic acid and hexadecylenic acid contributed to the higher degree of unsaturated fatty acids in 'Gannan No.1'. Furthermore, 'Gannan No.1' accumulated stress-resistant metabolites such as proline, α-tocopherol and glutathione. Correlation analysis of membrane homeostasis indexes with quality parameters showed the importance of biomembrane stability in maintaining citrus fruit quality.

Metabolic variation in the pulps of two durian cultivars: Unraveling the metabolites that contribute to the flavor.

Durian (Durio zibethinus M.) is a major economic fruit crop in Thailand. In this study, two popular cultivars, namely Chanee and Mon Thong, were collected from three orchards located in eastern Thailand. The pulp metabolome, including 157 annotated metabolites, was explored using capillary electrophoresis-time of flight/mass spectrometry (CE-TOF/MS). Cultivars and harvest years had more impact on metabolite profile separation than cultivation areas. We identified cultivar-dependent metabolite markers related to durian fruit quality traits, such as nutritional value (pyridoxamine), odor (cysteine, leucine), and ripening process (aminocyclopropane carboxylic acid). Interestingly, durian fruit were found to contain high amounts of γ-glutamylcysteine (810.3 ±â€¯257.5 mg/100 g dry weight) and glutathione (158.1 ±â€¯80.4 mg/100 g dry weight), which act as antioxidants and taste enhancers. This metabolite information could be related to consumer preferences and exploited for durian fruit quality improvement.

Laccase-mediated crosslinking of gluten-free amadumbe flour improves rheological properties.

The absence of gluten in gluten-free flours presents a challenge to their application in baking. Enzymatic modification of the protein and polysaccharides may result in a network that mimics gluten. In the current study, the effects of laccase on the rheological properties of amadumbe dough were investigated. Thiol and total phenolic contents of dough decreased by up to 28% and 93%, respectively, as laccase activity was increased (0-3 U/g flour). Both G' and G″ of laccase-treated dough increased significantly due to laccase-catalysed cross-linking of proteins and polysaccharides esterified with phenolics, as demonstrated by relevant model reactions. Tan δ decreased with increase in laccase activity indicating an increase in the elastic character of the dough. The improvement in dough viscoelasticity may enable the retention of adequate carbon dioxide during proofing and production of more acceptable gluten-free bread.

Persimmon vinegar polyphenols protect against hydrogen peroxide-induced cellular oxidative stress via Nrf2 signalling pathway.

Since polyphenols are known to exhibit antioxidative properties, we prepared and characterized persimmon vinegar polyphenols (PVP) in this study. Furthermore, we investigated the protective effect of PVP on hydrogen peroxide (H2O2)-induced oxidative stress in HepG2 cells and its underlying mechanisms. Our results showed that flavon-3-ols were the predominant polyphenols in PVP. Pre-treatment with PVP significantly decreased (p < 0.05) H2O2-induced cell damage in a dose-dependent manner, accompanied by decrease in lactate dehydrogenase (LDH) leakage, aminotransferase activities, and ROS accumulation. Moreover, PVP upregulated the expression of antioxidative enzymes, such as heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1), and increased the levels of glutathione. Western blotting results showed that PVP induced the nuclear translocation of nuclear factor (erythroid-derived-2)-related factor 2 (Nrf2). Taken together, our results indicated that PVP effectively protected HepG2 cells against oxidative stress via activation of the Nrf2 antioxidative pathway.