Antioxidant Defense Capability Research Articles

Anti-skin aging effect of sea buckthorn proanthocyanidins in D-galactose-induced aging mice.

Oxidative stress in skin cells caused by changes in the external environment is one of the principal causes of skin aging. Sea buckthorn proanthocyanidins (SBPs) have good free radical scavenging ability. We established a senescence model by injecting 500 mg/kg D-galactose into the dorsal necks of mice, and then different doses of SBP (25, 50, and 100 mg/kg) were gavaged to explore the effects of SBP on the skin tissues of senescent mice and elucidate the related mechanism of action. The results reveal that SBP can alleviate the skin aging phenomenon caused by D-galactose-induced aging. It can also enhance the total antioxidant capacity in the body, thereby strengthening the body's antioxidant defense capability. In addition, SBP can effectively improve skin aging by regulating the TGF-β1/Smads pathway and MMPs/TIMP system, increasing the relative content of Col I and tropoelastin, further maintaining the stability of collagen fiber and elastic fiber structure. These results will provide the development and production of the antioxidant function of cosmetics and health products, providing a new train of thought.

Exogenous abscisic acid improves grain filling capacity under heat stress by enhancing antioxidative defense capability in rice

BackgroundHeat stress is a major restrictive factor that causes yield loss in rice. We previously reported the priming effect of abscisic acid (ABA) on rice for enhanced thermotolerance at the germination, seedling and heading stages. In the present study, we aimed to understand the priming effect and mechanism of ABA on grain filling capacity in rice under heat stress.ResultsRice plants were pretreated with distilled water, 50 μM ABA and 10 μM fluridone by leaf spraying at 8 d or 15 d after initial heading (AIH) stage and then were subjected to heat stress conditions of 38 °C day/30 °C night for 7 days, respectively. Exogenous ABA pretreatment significantly super-activated the ABA signaling pathway and improved the SOD, POD, CAT and APX enzyme activity levels, as well as upregulated the ROS-scavenging genes; and decreased the heat stress-induced ROS content (O2– and H2O2) by 15.0–25.5% in rice grain under heat stress. ABA pretreatment also increased starch synthetase activities in rice grain under heat stress. Furthermore, ABA pretreatment significantly improved yield component indices and grain yield by 14.4–16.5% under heat stress. ABA pretreatment improved the milling quality and the quality of appearance and decreased the incidence of chalky kernels and chalkiness in rice grain and improved the rice grain cooking quality by improving starch content and gel consistence and decreasing the amylose percentage under heat stress. The application of paraquat caused overaccumulation of ROS, decreased starch synthetase activities and ultimately decreased starch content and grain yield. Exogenous antioxidants decreased ROS overaccumulation and increased starch content and grain yield under heat stress.ConclusionTaken together, these results suggest that exogenous ABA has a potential priming effect for enhancing rice grain filling capacity under heat stress at grain filling stage mainly by inhibiting ROS overaccumulation and improving starch synthetase activities in rice grain.

Alfalfa MsATG13 Confers Cold Stress Tolerance to Plants by Promoting Autophagy.

Autophagy is a conserved cellular process that functions in the maintenance of physiological and metabolic balance. It has previously been demonstrated to improve plant tolerance to abiotic stress. Numerous autophagy-related genes (ATGs) that regulate abiotic stress have been identified, but there have been few functional studies showing how ATGs confer cold stress tolerance. The cold transcriptome data of the crown buds that experienced overwintering of the alfalfa (Medicago sativa L.) showed that MsATG13 is upregulated in response to cold stress. In the present study, we found that MsATG13 transgenic tobacco enhanced cold tolerance compared to wild-type (WT) plants. Transmission electron microscopy demonstrated that transgenic tobacco overexpressing MsATG13 formed more autophagosomes than WT plants in response to cold stress conditions. The transgenic tobacco increased autophagy levels due to upregulation of other ATGs that were necessary for autophagosome production under cold stress conditions. MsATG13 transgenic tobacco also increased the proline contents and antioxidant enzyme activities, enhancing the antioxidant defense capabilities under cold stress conditions. Furthermore, MsATG13 overexpression decreased levels of superoxide anion radicals and hydrogen peroxide under cold stress conditions. These findings demonstrate the role of MsATG13 in enhancing plant cold tolerance through modulation of autophagy and antioxidant levels.

The Role of Reactive Oxygen Species in Muscle: Beneficial/Harmful

Introduction: Skeletal muscle produces moderate quantities of oxidant species, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), due to its contractile action, high oxygen consumption, and metabolic rate (RNS). Under normal physiological circumstances, the generation and removal of ROS/RNS are in dynamic equilibrium.
 Content: The body reaches a condition of oxidative stress, however, when the oxidation products surpass the antioxidant defense capability. Increased oxidative stress has significant ramifications for the molecular, structural, and functional integrity of muscle. The release of reactive oxygen species (ROS) under pathological circumstances leads to cellular dysfunction and the progression of muscle disorders.
 Conclusion: The antioxidants can put ROS in optimal concentrations to perform physiological signals in muscle. At appropriate concentrations, ROS and RNS can regulate intracellular signal transduction. Thus, moderate quantities of radicals are advantageous to muscle, but high doses of ROS are harmful. The aim of this review is to know about the role of ROS in muscle.

The p-hydroxybenzoic acid enhanced lipid accumulation of Chlorella under antibiotic stress

Phytohormones are widely known to regulate plant growth under environmental stress, however, their roles of microalgae are not clear during the antibiotic wastewater treatment. A hypothesis was proposed that phytohormones were capable to relieve the inhibition of microalgae growth and improve the bioresources recovery from antibiotic wastewater. Chlorella and enrofloxacin (ENR) were utilized to simulate the antibiotic wastewater treatment by microalgae, and explored the roles of p-hydroxybenzoic acid (pHBA). With 10 mg/L ENR and 1 μM pHBA condition, the Chlorella biomass increased by 23%. Moreover, lipid production increased by 30%. Trace amounts of pHBA improved microalgae growth and lipid accumulation by up-regulating photosynthesis, glycolysis, and TCA cycle. Furthermore, pHBA stimulated the signal transduction pathways of microalgae to improve antioxidant defense capability. Therefore, pHBA enhanced tolerance of ENR and improved microalgae lipid production. This study provided a new clue into using microalgae to recover high-value bioresources from antibiotic wastewater.

Effect of Salt Stress on Growth and Physiological Properties of Asparagus Seedlings.

Salt stress could inhibit the growth and development of crops and negatively affect yield and quality. The objective of this study was to investigate the physiological responses of different asparagus cultivars to salt stress. Twenty days old seedlings ofasalt-tolerant Apollo andasalt-sensitive cultivar JL1 were subjected to 0 (CK) and120 mM NaCl stress for 20 d. Their changes in growth, ion contents, antioxidant enzyme activities and gene expression were analyzed. Salt stress significantly inhibited the growth of both cultivars, and JL1 showed a greater decrease than Apollo. The root development of Apollo was promoted by 120 mM NaCl treatment. The Na+ content in roots, stems, and leaves of both cultivars was increased under salt stress, while K+ content and K+/Na+ decreased. The salt-tolerant cultivar Apollo showed less extent of increase in Na+ and decrease in K+ content and kept a relatively high K+/Na+ ratio to compare with JL1. The contents of proline, soluble sugar and protein increased in Apollo, while thesesubstances changed differently in JL1 under salt stress. Activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were gradually increased under salt stress in Apollo, while the corresponding enzyme activities in JL1 were decreased at the late stage of salt stress. The expression of SOD, POD, and CAT genes of both cultivars changed in a similar way to the enzyme activities. Malondialdehyde (MDA) content was increased slightly in Apollo, while increased significantly in JL1. At the late stage of salt stress, Apollomaintained a relatively high K+/Na+, osmotic adjustment ability and antioxidant defense capability, and therefore exhibited higher tolerance to salt stress than that of JL1.

Priming effect of exogenous ABA on heat stress tolerance in rice seedlings is associated with the upregulation of antioxidative defense capability and heat shock-related genes

Heat stress is a major restrictive factor that suppresses rice production. In this study, we investigated the potential priming effect of exogenous abscisic acid (ABA) on heat tolerance in rice seedlings. Seedlings were pretreated with 10 µM ABA by root-drenched for 24 h and then subjected to heat stress conditions of 40 °C day/35 °C night. ABA pretreatment significantly decreased leaf withering by 2.5–28.5% and chlorophyll loss by 12.8–35.1% induced by heat stress in rice seedlings. ABA pretreatment also mitigated cell injury, as shown by lower malondialdehyde content, relative electrolytic conductivity, and expression of cell death-related genes OsKOD1, OsCP1, and OsNAC4, while expression of OsBI1, a cell death-suppressor gene, was upregulated by ABA pretreatment. Moreover, ABA pretreatment improved antioxidant defense capacity, as shown by an obvious upregulation of ROS-scavenging genes and a decrease in ROS content (O2− and H2O2), and downregulation of the OsRbohs genes. Application of fluridone, an ABA biosynthesis inhibitor, increased membrane injury and the accumulation of ROS under heat stress. Exogenous antioxidants (proanthocyanidins) significantly alleviated leaf withering by decreasing ROS overaccumulation and membrane injury induced by heat stress. In addition, ABA pretreatment significantly superinduced the expression of ABA-responsive genes SalT and OsWsi18, the ABA biosynthesis genes OsNCED3 and OsNCED4, and the heat shock-related genes OsHSP23.7, OsHSP17.7, OsHSF7, and OsHsfA2a. Taken together, these results suggest that exogenous ABA has a potential priming effect for enhancing heat stress tolerance of rice seedlings mainly by improving antioxidant defense capacity and heat shock-related genes.

Recent Insights into the Nutritional Antioxidant Therapy in Prevention and Treatment of Diabetic Vascular Complications: A Comprehensive Review.

Diabetes mellitus (DM) and DM-induced vascular complications are significant global healthcare problems, causing a decrease in patient quality of life. The main reason for the disability and mortality of patients is rapidly progressing micro-and macroangiopathies. Currently, free radical oxidation is recognized as one of the main mechanisms in the development of DM and associated complications. Under normal physiological conditions, the level of free radicals and antioxidant defense capabilities is balanced. However, imbalance occurs between the antioxidant defense system and pro-oxidants during chronic hyperglycemia and may invoke the formation of excess free radicals, leading to activation of lipid peroxidation and accumulation of highly toxic products of free radical oxidation. This is accompanied by varying degrees of insulin deficiency and insulin resistance in DM patients. Simultaneously with the activation of free radical generation, a decrease in the activity of antioxidant defense factors (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, vitamins C and E) and an acceleration of diabetic complications are seen. Therefore, we hypothesize that antioxidants may play a positive role in the treatment of DM patients to prevent DM-induced vascular complications. However, this has not been sufficiently studied. In this review, we discuss recent insights into the potential underlying mechanisms of oxidative stress-induced diabetic complications and the implications of antioxidants in mitigation of DM-induced vascular complications.

Spatiotemporal sonodynamic therapy for the treatment of rheumatoid arthritis based on Z-scheme heterostructure sonosensitizer of HO-1 inhibitor jointed bismuth nanotriangle

Although some advances in rheumatoid arthritis (RA) clinical therapy, treatment discontinuation and suboptimal response to therapy are yet unresolved challenges. Sonodynamic therapy (SDT) has drawn great attention in bio-applications, owing to its superiorities such as non-invasiveness and better penetration depth. However, SDT efficiency is restricted by inefficient electron (e-)-hole (h+) separation in sonosensitizer and O2 deficiency in RA. In this study, we for the first time designed a Z-scheme heterostructure sonosensitizer based on bismuth nanotriangles (Bi NTs) jointed heme oxygenase (HO-1) inhibitor (zinc protoporphyrin IX, ZnPP) with effective e--h+ separation capacity and high redox potentials. ZnPP would be pre-bonded to the overexpressed HO-1 in inflammatory joint fluid to suppress the antioxidant defense capability, thus reducing the ROS consumption. The nanoplatform could be activated by sono to achieve O2 and ROS synchronous production. The obtained O2 could alleviate hypoxia in inflamed joints to relieve synovial erosion and pannus. Then, the generated ROS could amplify the oxidative stress, which is associated with the release of cytochrome C, to trigger caspase-dependent apoptosis rather than necrosis to avoid further inflammation. The Z-scheme heterostructure Bi NTs-ZnPP/HSA overcomes the major obstacles of conventional sonosensitizer during the RA-SDT process and supplies a new strategy for RA treatment..

Effects of Zinc Adaptation on Histological Morphology, Antioxidant Responses, and Expression of Immune-Related Genes of Grass Carp (Ctenopharyngodon idella).

The study was conducted to evaluate the effect of zinc adaptation on histological morphology and antioxidant and immune responses of grass carp(Ctenopharyngodon idella). A total of 180 young grass carp (20.0 ± 2.0g) was equally distributed into 9 groups, and triplicate groups were subjected to 0μg/L Zn2+ (control group), 200μg/L Zn2+, and 300μg/L Zn2+ solution for 42days, respectively. The results indicated that the liver and gill have obvious pathological changes after long-term adaptation to zinc except the intestine; the zinc adaptation can positively influence intestinal morphology. The activities of GPX (glutathione peroxidase activity), SOD (superoxide dismutase), and CAT (Catalase) were significantly increased in zinc treatment groups (P < 0.05). The genes expression levels of CuZnSOD (copper zinc superoxide dismutase), CAT, Hsp70 (heat shock protein-70), IL-1b (interleukin-1-b), and TGF-β1 (transforminggrowthfactor-β1) were upregulated in the gill and intestine of grass carp following waterborne adaptation to zinc solution for 42days (P < 0.05). In conclusion, zinc adaptation has different effects on organs of grass carp and may reduce the inflammatory response of the body's gills and intestines by improving the body's antioxidant and anti-stress defense capabilities.

The level of carbonylation of plasma proteins and peripheral blood leukocytes in patients with different duration of Alzheimer’s disease

The course of Alzheimer’s disease is associated with an increase in oxidative stress associated with an increase in the production of reactive oxygen species against the background of neurodegenerative inflammation, and a simultaneous depletion of the antioxidant defense capabilities of brain cells. The result is the oxidative modification of macromolecules: proteins, lipids, nucleic acids. Protein carbonylation products accumulate not only in neurons, and in direct correlation with the degree of increase in amyloidosis and neurodegeneration, but also in extra-neuronal tissues, including leukocytes. In the course of this study, the levels of spontaneous and induced oxidative modification of proteins were determined in the blood plasma and fractionated leukocytes of peripheral blood of patients with different durations of Alzheimer’s disease, and the value of the reserve-adaptive potential was assessed as markers of the severity of oxidative stress. It has been established that the course of Alzheimer’s disease has a greater effect on the accumulation of carbonyl derivatives in blood plasma. In patients with a disease duration of 5–10 years, the total level of aldehyde and ketone derivatives of modified plasma proteins exceeds the same indicator in subgroups with a shorter duration of the disease. This tendency is less typical for mononuclear leukocytes. The level of induced oxidative modification of proteins increases to a greater extent in blood plasma than in fractionated leukocytes. This indicates the depletion of the reserve-adaptive potential of plasma antioxidant capabilities, which is more pronounced in patients with a long course of Alzheimer’s disease. For polymorphonuclear leukocytes, such a pattern was not revealed, which is probably associated with a short cell life. In mononuclear leukocytes, as well as in plasma, there is a tendency to depletion of the reserve-adaptive potential, but to a lesser extent.

Maintenance of root water uptake contributes to salt-tolerance of a wild tomato species under salt stress

ABSTRACT Under salt stress, the regulatory mechanism of root water uptake in tomato species with different salt-tolerance remains unclear. Here, we compared water uptake, aquaporin expression and oxidative damage in roots of wild tomato Solanum pimpinellifolium ‘L03708ʹ and cultivated tomato Solanum lycopersicum ‘M82ʹ under salt stress (150 mM NaCl) and H2O2-caused oxidative stress which is usually induced by salt stress. The results showed that the seedling growth was inhibited and root hydraulic conductance in ‘M82ʹ was decreased under salt stress, whereas these were unchanged in ‘L03708ʹ. Under salt stress, the PIP1 aquaporin abundance was decreased in ‘M82ʹ but unchanged in ‘L03708ʹ, and the PIP2 abundance was decreased in both species. The membrane damage and hydrogen peroxide accumulation were more severe in ‘M82ʹ than ‘L03708ʹ under salt stress. Exogenous H2O2 increased the membrane electrolyte leakage and decreased the root hydraulic conductance, with the changes being more profound in ‘M82ʹ than ‘L03708ʹ. The PIP1 abundance was increased in ‘L03708ʹ but decreased in ‘M82ʹ by H2O2 treatment. These results suggest that the maintenance of PIP1 abundance and antioxidant defense capability in the wild tomato species may contribute to its maintenance of root water uptake and thus salt-tolerance under salt stress.

Exogenous application of ascorbic acid mitigates cadmium toxicity and uptake in Maize (Zea mays L.).

Cadmium (Cd) contamination in agricultural soils is a prevalent environmental issue and poses potential threats to food security. Foliar ascorbic acid might prove a potent tool to alleviate toxicity of Cd toxicity in maize. An experiment was conducted with objectives to study exogenous ascorbic acid-modulated improvements in physiochemical attributes of maize under Cd toxicity. The experiment was conducted under completely randomized design. Treatments were comprised of varying concentrations of foliar ascorbic acid viz. 0.0, 0.1, 0.3, and 0.5 mM of AsA. Toxicity of Cd decreased the maize growth, increased lipid peroxidation, disturbed protein metabolism, and reduced the antioxidant defense capabilities compared with the control. However, foliar AsA significantly improved maize growth and development, photosynthetic capabilities, and protein concentrations in Cd-stressed maize plants. Meanwhile, the malondialdehyde contents and hydrogen peroxide accumulation levels in Cd-stressed maize plants decreased remarkably with increasing AsA concentrations. Furthermore, the combined treatments conspicuously boosted activities of superoxide dismutase, peroxidase, catalase, and glutathione reductase under the Cd stress alone. In addition, the application of AsA reduced the Cd uptake by 10.3-12.3% in grains. Conclusively, foliar ascorbic acid alleviated the negative effects of Cd stress in maize and improved photosynthetic processes, osmolytes, and antioxidant defense systems.

Bismuth Sulfide Nanorods with Retractable Zinc Protoporphyrin Molecules for Suppressing Innate Antioxidant Defense System and Strengthening Phototherapeutic Effects

Bismuth (Bi)-based nanomaterials (NMs) are widely used for computed tomography (CT) imaging guided photothermal therapy, however, the photodynamic property is hardly exhibited by these NMs due to the fast electron-hole recombination within their narrow bandgap. Herein, a sophisticated nanosystem is designed to endow bismuth sulfide (Bi2 S3 ) nanorods (NRs) with potent photodynamic property. Zinc protoporphyrin IX (ZP) is linked to Bi2 S3 NRs through a thermoresponsive polymer to form BPZP nanosystems. The stretching ZP could prebind to the active site of heme oxygenase-1 overexpressed in cancer cells, suppressing the cellular antioxidant defense capability. Upon NIR laser irradiation, the heat released from Bi2 S3 NRs could retract the polymer and drive ZP to the proximity of Bi2 S3 NRs, facilitating an efficient electron-hole separation in ZP and Bi2 S3 NRs, and leading to reactive oxygen species generation. In vitro and in vivo studies demonstrate the promising photodynamic property of BPZP, together with their photothermal and CT imaging performance.

Peroxisomal Malfunction Caused by Mitochondrial Toxin 3-NP: Protective Role of Oxytocin.

Peroxisomes are single membrane cell organelles with a diversity of metabolic functions. Here we studied the peroxisomal dysfunction and oxidative stress after 3-nitropropionic acid (3-NP) induced neurotoxicity and the possible protective effects of oxytocin. Adult male and female rats were subjected to OXT and/or 3-NP treatment. The antioxidant enzymes, Superoxide dismutase (SOD) and Catalase (CAT) activities as well as expression level of Peroxin 14 (Pex14), a marker for peroxisomal number and Peroxisomal membrane protein of 70 kDa (PMP70), a metabolic transporter in peroxisome in different brain regions of both sexes were studied. The results indicated that 3-NP significantly decreased the expression level of Pex14 and PMP70 in various studied areas in male and female rats. In addition, 3-NP reduced the SOD and CAT activity in different brain regions in both sexes. OXT treatment increased the expression level of peroxisomal proteins Pex14 and PMP70 which are representative of peroxisome performance improvement. Besides, it ameliorated the antioxidant system capability through increasing the activity of the SOD and CAT in all studied brain regions including Striatum, Hippocampus, Prefrontal Cortex and Amygdala with no differences in male and female rats. This study demonstrated that toxin 3-NP, could ultimately cause peroxisomal malfunction and so determines the contribution of peroxisomal dysfunction in the etiology of HD pathology. OXT significantly increased peroxisomal function and antioxidant system defense capability, therefore illustrates that OXT might be an alternate treatment approach for the neurodegenerative diseases like HD.

Recent advances in mitochondria-targetable organic molecule fluorescent probes for imaging of ROS

Mitochondria, as the “energy power house” of the cell, utilize the oxygen to engage in oxidative phosphorylation accompanying production of triphosadenine (ATP), which will supply energy for the cell and organism. Meanwhile, various reactive oxygen species (ROS) will produce rapidly in mitochondria coupling with the electron leak in respiratory chain. The mitochondrial ROS plays important function in many processes, such as maintaining redox equilibrium, regulating cellular proliferation, differentiation and apoptosis. When the level of ROS exceeds the antioxidant defense capability of organism, various diseases will appear. Therefore, developing new methods to detect the level of ROS in mitochondria is of great importance for exploring the functional regulation effect of ROS. It’s still a huge challenge to accurately monitor ROS for chemistry, biology and medicine due to the properties of ROS, including low concentration, short lifetime and high reactivity. Fluorescence imaging is a powerful tool to track ROS in live cell and in vivo , because of its remarkable advantages, such as high temporal-spatial resolution, excellent biocompatibility and high sensitivity. In recent years, many fluorescent probes have been developed and applied for fluorescence imaging of ROS within mitochondria. In this review, we mainly summarize the progress of mitochondria-targetable organic small molecule fluorescent probes for detection of various ROS. Furthermore, future research directions for the construction of novel mitochondrial fluorescent probes as well as dissection of the cellular function of ROS by utilizing fluorescence imaging are prospected.

Oxygen exchange and energy metabolism in erythrocytes of Rett syndrome and their relationships with respiratory alterations.

Rett syndrome (RTT) is a neurodevelopmental disorder, mainly affecting females, which is associated to a mutation on the methyl-CpG-binding protein 2 gene. In the pathogenesis and progression of classic RTT, red blood cell (RBC) morphology has been shown to be an important biosensor for redox imbalance and chronic hypoxemia. Here we have evaluated the impact of oxidation and redox imbalance on several functional properties of RTT erythrocytes. In particular, we report for the first time a stopped-flow measurement of the kinetics of oxygen release by RBCs and the analysis of the intrinsic affinity of the hemoglobin (Hb). According to our experimental approach, RBCs from RTT patients do not show any intrinsic difference with respect to those from healthy controls neither in Hb's oxygen-binding affinity nor in O2 exchange processes at 37°C. Therefore, these factors do not contribute to the observed alteration of the respiratory function in RTT patients. Moreover, the energy metabolism of RBCs, from both RTT patients and controls, was evaluated by ion-pairing HPLC method and related to the level of malondialdehyde and to the oxidative radical scavenging capacity of red cells. Results have clearly confirmed significant alterations in antioxidant defense capability, adding important informations concerning the high-energy compound levels in RBCs of RTT subjects, underlying possible correlations with inflammatory tissue alterations.

English

This study aims to determine the toxicity, genotoxicity and antioxidative defense capacities of isopentanyl ferulate (IF), an ester derivative of ferulic acid (FA). Therefore, albino mice (25-30 g) were treated with 1000 to 3000 mg/kg orally (p.o.) and intraperitoneally (i.p.) to determine median lethal dose (LD50), biochemical and hematological parameters, motor coordination and genotoxic activity by comet assay. In addition, oxidative defense was assessed in Saccharomyces cerevisiae with one proficient (Sod wt), three single mutant (Sod1∆, Sod2∆ and Cat1∆) and two double mutants (Sod1∆Sod2∆ and Sod1∆Cat1∆), where IF in a dose range of 0.10 to 0.30 g/ml was used. Results suggest that IF produced LD50 by 1494.54 mg/kg. There was a bit change in biochemical and hematological parameters compared to the control group. Although, IF did not affect locomotor activity in test animals (both sexes) assessed by open field test (OFT) but it produced genotoxic activity at doses 1500 mg/kg (i.p.) and 3000 mg/kg (p.o.), whosever is higher than the LD50. Antioxidative defense to the S. cerevisiae cells and damage repair capability in both comet and S. cerevisiae assays indicate IF for a promising pharmacological moiety. In conclusion, IF produced low toxicity, genotoxicity at high dose with antioxidative defense and damage repair capability. Key words: Antioxidant, genotoxicity, isopentanyl ferulate, toxicity.

Abstract 4310: Regular intake of high-fat diet exacerbates oxidative stress-mediated DNA hypermethylation and activation of Nrf2-Keap1 signaling in UVB-induced skin tumors in SKH-1 hairless mice

Abstract Generation of reactive oxygen species (ROS) is an essential metabolic process for maintaining normal cellular homeostasis; however elevated and sustained levels of ROS contribute in many human diseases, including cancer. Sustained and excessive cellular ROS result in genetic as well as epigenetic alterations, leading to deregulation of oncogenes and tumor suppressor genes. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a ubiquitous transcription factor, capable of eliciting the coordinated induction of cytoprotective genes in response to oxidative stress. Upon oxidative insult, Nrf2 rapidly translocate to nucleus, activates genes encoding anti-oxidative enzymes such as heme oxygenase 1 (HO-1) and superoxide dismutase (SOD). Earlier, we have shown that regular intake of high-fat diet (HF-diet) enhances tumor development in UV-exposed SKH-1 hairless mouse skin compared to control-diet (C-diet) fed mice. Administration of HF-diet along with exposure of UVB radiation (180 mJ/cm2, 3x/week for 24 weeks) resulted in sustained oxidative stress as evident by depletion in antioxidant defense capabilities. The levels of reduced glutathione (40%, p&amp;lt;0.001), glutathione peroxidase (49%, p&amp;lt;0.001) and SOD (47%, p&amp;lt;0.001) were noted, while the level of lipid peroxidation was significantly increased (160%, p&amp;lt;0.001) in skin tumors of HF-diet fed mice compared with C-diet fed mice. Epigenetic alterations in association with oxidative stress were analyzed by estimation of global DNA methylation, DNA methyltransferase (Dnmt) activity and histone modifications. We observed significant increase of Dnmt activity (3 fold, p&amp;lt;0.001) and global DNA methylation level (2 folds, p&amp;lt;0.001) along with Dnmt proteins and methylated histone in tumors of HF-diet fed mice compared with tumors of C-diet fed mice. Oxidative stress disrupts Nrf2-Keap-1 binding by DNA hypermethylation and epigenetic silencing of Keap1 gene leading to its inactivation, release and translocation of Nrf2 to nucleus. Our RT-PCR data showed elevated levels of methylated Keap-1 and lower levels of un-methylated Keap-1 gene in skin tumors from HF-diet fed mice. Disruption of Keap-Nrf2 binding resulted in higher nuclear translocation of Nrf2 and activation of its target genes NQO-1 and HO-1 as confirmed by western blot analyses. Taken together, this study shows that chronic exposure to UVB along with administration of HF-diet induces oxidative stress, causes epigenetic modifications and loss of Keap1 function leading to nuclear accumulation of Nrf2 which creates a susceptible environment for skin tumor growth. Citation Format: Tripti Singh, Ram Prasad, Santosh K. Katiyar. Regular intake of high-fat diet exacerbates oxidative stress-mediated DNA hypermethylation and activation of Nrf2-Keap1 signaling in UVB-induced skin tumors in SKH-1 hairless mice. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4310.

Changes in Antioxidant Defense Capability and Lipid Profile after 12-Week Low- Intensity Continuous Training in Both Cigarette and Hookah Smokers: A Follow-Up Study

To examine the impact of low-intensity continuous training program on antioxidant defense capability and lipid profile in male cigarette or hookah smokers. Forty-three male adults participated in a 12-week continuous training program at an intensity of 40% of VO2max. All subjects were subjected to anthropometric, physical and biochemical tests before and after the training program. The increase of Glutathione reductase (GR) and Superoxide dismutase (SOD) is significant only for cigarette smokers (CS) and hookah smokers (HS) groups. The Malondialdehyde (MDA) decrease and α-tocopherol increase are significant only for HS group. GPx was increased in NS, CS and HS by 2.6% (p< 0.01), 2% (p< 0.05) and 1.7% (p< 0.05) respectively. Likewise, significant improvements of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and TC / HDL-C ratio were observed in three groups. En contrast no significant changes were recorded in triglycerides (TG). Also, significant reduction of total cholesterol (TC) for CS group (p< 0.01) and HS groups (p< 0.05). This continuous training program appears to have an important role in lipid levels improving and oxidative stress attenuation.