Upregulation Of Antioxidant Enzymes Research Articles

Role of Zinc Oxide Nanoparticles in Countering Negative Effects Generated by Cadmium in Lycopersicon esculentum

Nanotechnology now plays a revolutionary role in many applications; nanomaterials have experienced significant importance in both basic and applied sciences as well as in bio-nanotechnology. Zinc oxide nanoparticles (ZnO-NPs) have become one of the most important metal oxide NPs in biological applications due to their beneficial impacts. The purpose of this study was to explore the effects of ZnO-NPs in reducing Cd toxicity by studying the growth, photosynthesis reactions, antioxidant system, oxidative stress, and protein content in Lycopersicon esculentum (tomato). ZnO-NPs induced an upregulation of antioxidative enzymes which protect the photosynthetic apparatus in plants. Seeds of tomato were sown to create nursery. At 20 days after sowing (DAS), seedlings were transferred to soil pots. Varied concentrations (0.4, 0.6 or 0.8 mM) of Cd were applied to the soil after 24 and 25 DAS. Zinc (Zn; 50 mg/L) and ZnO-NPs (50 mg/L) treatments were given continuously for 5 days from 31 to 35 DAS and sampling took place at 45 DAS. The results indicate that a Cd-generated oxidative burst in the form of elevated hydrogen peroxide (H2O2) levels resulted in a decline in cell viability through enhanced activity of the antioxidant system and proline content; the data increased on follow-up treatment with ZnO-NPs. Foliar application of ZnO-NPs significantly enhanced plant height, fresh, and dry weight of plant, leaf area, SPAD chlorophyll, photosynthetic attributes, i.e., net photosynthetic rate (PN), transpiration rate (E), internal CO2 concentration (Ci), and stomatal conductance (gs). Application of ZnO-NPs reduced the adverse effects generated by Cd and increased protein content, activities of nitrate reductase and carbonic anhydrase over the control in both stressed and non-stressed plants. Additionally, microscopic studies showed a marked increase in stomatal aperture after ZnO-NPs treatment in the presence or absence of Cd. This was associated with decrease in malondialdehyde and superoxide radical (O2−) levels. The present study suggests that ZnO-NPs can be effectively used to reduce the toxicity of Cd in tomato plants and may also be suitable for testing on other crop species.

Nano-silver and non-traditional compounds mitigate the adverse effects of net blotch disease of barley in correlation with up-regulation of antioxidant enzymes

Nano-silver and non-traditional compounds mitigate the adverse effects of net blotch disease of barley in correlation with up-regulation of antioxidant enzymes

A Solid Dispersion of Quercetin Shows Enhanced Nrf2 Activation and Protective Effects against Oxidative Injury in a Mouse Model of Dry Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) represents a major reason for blindness in the elderly population. Oxidative stress is a predominant factor in the pathology of AMD. We previously evaluated the effects of phospholipid complex of quercetin (Q-PC) on oxidative injury in ARPE-19 cells, but the underlying mechanisms are not fully understood. Herein, the solid dispersion of quercetin-PC (Q-SD) was prepared with solubility being 235.54 μg/mL in water and 2.3×104 μg/mL in chloroform, which were significantly higher than that of quercetin (QT) and Q-PC. Q-SD also exhibited a considerably higher dissolution rate than QT and Q-PC. Additionally, Q-SD had Cmax of 4.143 μg/mL and AUC of 12.015 μg·h/mL in rats, suggesting better bioavailability than QT and Q-PC. Then, a mouse model of dry AMD (Nrf2 wild-type (WT) and Nrf2 knockout (KO)) was established for evaluating the effects of Q-SD in vivo. Q-SD more potently reduced retinal pigment epithelium sediments and Bruch's membrane thickness than QT and Q-PC at 200 mg/kg in Nrf2 WT mice and did not work in Nrf2 KO mice at the same dosage. Additionally, Q-SD significantly decreased ROS and MDA contents and restored SOD, GSH-PX, and CAT activities of serum and retinal tissues in Nrf2 WT mice, but not in Nrf2 KO mice. Furthermore, Q-SD more potently increased Nrf2 mRNA expression and stimulated its nuclear translocation in retinal tissues of Nrf2 WT mice. Q-SD significantly increased the expression of Nrf2 target genes HO-1, HQO-1, and GCL of retinal tissues in Nrf2 WT mice, not in Nrf2 KO mice. Altogether, Q-SD had improved physicochemical and pharmacokinetic properties compared to QT and Q-PC and exhibited more potent protective effects on retina oxidative injury in vivo. These effects were associated with activation of Nrf2 signaling and upregulation of antioxidant enzymes.

Bromelain plus peroxidase reduces non-Hodgkin lymphoma progression in invivo via up-regulation of antioxidant enzymes and modulating apoptotic protein expression

Aim: Pineapple (Ananas comosus (L.) Merr.) is a good source of bromelain (B) and also contain peroxidase. The objective of this study is isoaltion of bromelain plus peroxidase (BP) from the pineapple fruit to evaluate the anticancer activity of BP from the pineapple fruit of Tripura, compared to commercial bromelain against ascitic Dalton’s lymphoma cells (DLA) in mice. Methods: By acetone precipitation BP was isolated from the pineapple. Animals bearing DLA, receive B and BP orally for 15 alternative days. Apoptotic proteins are assayed using western blot. Results: BP treated mice showed recover of hemoglobin and WBC count compared to control lymphoma animal. The animal showed significant reduction of body weight due to reduced tunor load and elevated reactive oxygen species (ROS) production, elevated levels of vitamin C and vitamin E and other antioxidants in blood after BP treatment. Histology of liver and kidney also shows restored architecture in BP treated animal compared to only B treated group. BP treatment upregulates the cytochrome C, BAD, and BAX protein and downregulates the Bcl-2 and NF-kβ occuring upon BP treatment in the DLA cells collected from lymphoma animal. This induce the apoptosis of DLA cells in lymphoma animal and reduce the tumor load. Conclusion: The present findings suggest that BP from pineapple improves the survival of the induced lymphoma animal compared to only B which may be used as therapeutic target.

Beneficial Role of ROS in Cell Survival: Moderate Increases in H2O2 Production Induced by Hepatocyte Isolation Mediate Stress Adaptation and Enhanced Survival.

High levels of reactive oxygen species (ROS) can lead to impairment of cell structure, biomolecules’ loss of function and cell death and are associated with liver diseases. Cells that survive increased ROS often undergo malignant transformation. Many cancer cells tolerate high levels of ROS. Here we report a transiently increased production of H2O2 and concomitant upregulation of antioxidative enzymes triggered by hepatocyte isolation; the H2O2 levels revert in about two days in culture. Three-day survival rate of the isolated cells in the presence of 2.5-fold increase of H2O2 is almost 80%. Apoptosis activation through the mitochondrial pathway is meanwhile reduced by inhibition of caspase-9 triggering. This reduction depends on the amount of H2O2 production, as decreased production of H2O2 in the presence of an antioxidant results in increased apoptosis triggering. These stress adaptations do not influence urea production, which is unchanged throughout the normal and stress adapted phases. We conclude that hepatocytes’ stress adaptation is mediated by increased ROS production. In this case, high ROS improve cell survival.

The H2S-Nrf2-Antioxidant Proteins Axis Protects Renal Tubular Epithelial Cells of the Native Hibernator Syrian Hamster from Reoxygenation-Induced Cell Death.

During hibernation, repeated cycles of ischemia-reperfusion (I-R) leave vital organs without injury. Studying this phenomenon may reveal pathways applicable to improving outcomes in I-R injury-induced human diseases. We evaluated whether the H2S–nuclear factor erythroid 2-like 2 (Nrf2)–antioxidant proteins axis protects renal proximal tubular epithelial cells (RPTECs) of the native hibernator, the Syrian hamster, from reperfusion-induced cell death. To imitate I-R, the hamsters’, and control mice’s RPTECs were subjected to warm anoxia, washed, and then subjected to reoxygenation in fresh culture medium. Whenever required, the H2S-producing enzymes inhibitor aminooxyacetate or the lipid peroxidation inhibitor α-tocopherol were used. A handmade H2S detection methylene blue assay, a reactive oxygen species (ROS) detection kit, a LDH release cytotoxicity assay kit, and western blotting were used. Reoxygenation upregulated the H2S-producing enzymes cystathionine beta-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase in the hamster, but not in mouse RPTECs. As a result, H2S production increased only in the hamster RPTECs under reoxygenation conditions. Nrf2 expression followed the alterations of H2S production leading to an enhanced level of the antioxidant enzymes superoxide dismutase 3 and glutathione reductase, and anti-ferroptotic proteins ferritin H and cystine-glutamate antiporter. The upregulated antioxidant enzymes and anti-ferroptotic proteins controlled ROS production and rescued hamster RPTECs from reoxygenation-induced, lipid peroxidation-mediated cell death. In conclusion, in RPTECs of the native hibernator Syrian hamster, reoxygenation activates the H2S–Nrf2–antioxidant proteins axis, which rescues cells from reoxygenation-induced cell death. Further studies may reveal that the therapeutic activation of this axis in non-hibernating species, including humans, may be beneficial in I-R injury-induced diseases.

Exercise training upregulates Nrf2 protein in the rostral ventrolateral medulla of mice with heart failure.

Chronic heart failure (CHF) is associated with global oxidative stress, which contributes to sympathoexcitation. Increased reactive oxygen species in the brain accumulate within neurons and lead to enhanced neuronal excitability. Exercise training (ExT) is associated with a reduction of oxidative stress by upregulation of antioxidant enzymes. The link between ExT and antioxidant enzyme expression in the brain of animals with CHF is not clear. We hypothesized that ExT enhances transcription and translation of the nuclear factor erythroid 2-related factor 2 (Nrf2) gene, a master transcription factor that modulates antioxidant enzyme gene expression, in the rostral ventrolateral medulla (RVLM) of mice with CHF. Mice were divided into the following groups: Sham sedentary (Sham-Sed), Sham-ExT, CHF-Sed, and CHF-ExT. After 8 wk of ExT, we measured Nrf2 and NAD(P)H dehydrogenase [quinone] 1 (NQO-1) message and protein expression along with maximal exercise tolerance and urinary norepinephrine (NE) excretion. We found that Nrf2 and NQO-1 mRNA and protein expression in the RVLM were lower in CHF-Sed mice compared with Sham-Sed. ExT attenuated the CHF-induced reduction of Nrf2 and NQO-1 mRNA and protein expression in the RVLM. NE excretion was higher in CHF-Sed mice compared with Sham-Sed (666.8 ± 79.3 ng/24 h, n = 6 vs. 397.8 ± 43.7 ng/24 h, P = 0.04). CHF-ExT mice exhibited reduced urinary NE excretion compared with CHF-Sed (360.7 ± 41.7 ng, n = 4 vs. 666.8 ± 79.3 ng, n = 6; P = 0.03). We conclude that ExT-induced upregulation of Nrf2 in the RVLM contributes to the beneficial effects of ExT on sympathetic function in the heart failure state.NEW & NOTEWORTHY This study provide evidence for an important role for exercise training in the modulation of antioxidant enzyme production in the rostral ventrolateral medulla (RVLM) in the heart failure state. We show here a correlation between exercise training and the expression of the antioxidant transcription factor Nrf2 in the RVLM. Exercise training reduced sympathetic function (norepinephrine excretion) and upregulated both Nrf2 and the antioxidant enzyme NQO-1. We conclude that Nrf2 in the RVLM may be an important target for controlling sympathetic outflow in heart failure.

Combined Treatment with Three Natural Antioxidants Enhances Neuroprotection in a SH-SY5Y 3D Culture Model.

Currently, the majority of cell-based studies on neurodegeneration are carried out on two-dimensional cultured cells that do not represent the cells residing in the complex microenvironment of the brain. Recent evidence has suggested that three-dimensional (3D) in vitro microenvironments may better model key features of brain tissues in order to study molecular mechanisms at the base of neurodegeneration. So far, no drugs have been discovered to prevent or halt the progression of neurodegenerative disorders. New therapeutic interventions can come from phytochemicals that have a broad spectrum of biological activities. On this basis, we evaluated the neuroprotective effect of three phytochemicals (sulforaphane, epigallocatechin gallate, and plumbagin) alone or in combination, focusing on their ability to counteract oxidative stress. The combined treatment was found to be more effective than the single treatments. In particular, the combined treatment increased cell viability and reduced glutathione (GSH) levels, upregulated antioxidant enzymes and insulin-degrading enzymes, and downregulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 and 2 in respect to peroxide-treated cells. Our data suggest that a combination of different phytochemicals could be more effective than a single compound in counteracting neurodegeneration, probably thanks to a pleiotropic mechanism of action.

Regulator of G protein signaling 12 enhances osteoclastogenesis by suppressing Nrf2-dependent antioxidant proteins to promote the generation of reactive oxygen species.

Regulators of G-protein Signaling are a conserved family of proteins required in various biological processes including cell differentiation. We previously demonstrated that Rgs12 is essential for osteoclast differentiation and its deletion in vivo protected mice against pathological bone loss. To characterize its mechanism in osteoclastogenesis, we selectively deleted Rgs12 in C57BL/6J mice targeting osteoclast precursors using LyzM-driven Cre mice or overexpressed Rgs12 in RAW264.7 cells. Rgs12 deletion in vivo led to an osteopetrotic phenotype evidenced by increased trabecular bone, decreased osteoclast number and activity but no change in osteoblast number and bone formation. Rgs12 overexpression increased osteoclast number and size, and bone resorption activity. Proteomics analysis of Rgs12-depleted osteoclasts identified an upregulation of antioxidant enzymes under the transcriptional regulation of Nrf2, the master regulator of oxidative stress. We confirmed an increase of Nrf2 activity and impaired reactive oxygen species production in Rgs12-deficient cells. Conversely, Rgs12 overexpression suppressed Nrf2 through a mechanism dependent on the 26S proteasome, and promoted RANKL-induced phosphorylation of ERK1/2 and NFκB, which was abrogated by antioxidant treatment. Our study therefore identified a novel role of Rgs12 in regulating Nrf2, thereby controlling cellular redox state and osteoclast differentiation.

Nutritional modulation of the antioxidant capacities in poultry: the case of vitamin E.

Commercial poultry production is associated with a range of stresses, including environmental, technological, nutritional, and internal/biological ones, responsible for decreased productive and reproductive performance of poultry. At the molecular level, most of them are associated with oxidative stress and damages to important biological molecules. Poultry feed contains a range of feed-derived and supplemented antioxidants and, among them, vitamin E is considered as the "headquarters" of the antioxidant defense network. It is well-established that dietary supplementation of selenium, vitamin E, and carotenoids can modulate antioxidant defenses in poultry. The aim of the present paper is to present evidence related to modulation of the antioxidant capacities in poultry by vitamin E. Using 3 model systems including poultry breeders/males, semen, and chicken embryo/postnatal chickens, the possibility of modulation of the antioxidant defense mechanisms has been clearly demonstrated. It was shown that increased vitamin E supplementation in the breeder's or cockerel's diet increased their resistance to various stresses, including high polyunsaturated fatty acids (PUFA), mycotoxin, or heat stress. Increased vitamin E supplementation of poultry males was shown to be associated with significant increases in α-tocopherol level in semen associated with an increased resistance to oxidative stress imposed by various external stressors. Similarly, increased vitamin E concentration in the egg yolk due to dietary supplementation was shown to be associated with increased α-tocopherol concentration in the tissues of the developing embryos and newly hatched chicks resulting in increased antioxidant defenses and decreased lipid peroxidation. Furthermore, increased vitamin E transfer from the feed to egg yolk and further to the developing embryo was shown to be associated with upregulation of antioxidant enzymes reflecting antioxidant system regulation and adaptation. The role of vitamin E in cell signaling and gene expression as well as in interaction with microbiota and maintaining gut health in poultry awaits further investigation.

Dimethyl-β-propiothetine (DMPT) supplementation under the all-plant protein diet enhances growth performance, digestive capacity and intestinal structural integrity for on-growing grass carp (Ctenopharyngodon idella)

This study aimed to investigate the effects of dimethyl-β-propiothetine (DMPT) supplementation under the all-plant protein diet on the growth, digestive capacity, oxidative damage and intestinal structural integrity of on-growing young grass carp (Ctenopharyngodon idella). A total of 540 healthy grass carp (216 ± 0.29 g) were randomly divided into six groups with three replicates and fed one fish meal (FM) diet and five all-plant protein diets with graded levels of DMPT (0 to 520 mg/kg diet) for 60 days. The results indicated that compared to the FM diet group, the all-plant protein diet without DMPT supplementation (all-plant protein diet group) significantly reduced feed intake (FI), specific growth rate (SGR), percentage weight gain (PWG), and digestive enzyme activities (trypsin, chymotrypsin, lipase and amylase activities) as well as damaged the intestinal histological structure of fish. However, these parameters could be restored to levels equal or superior to the FM diet group at DMPT supplementation levels under the all-plant protein diet up to 260.00 mg/kg diet. This is the first study to show that (1) DMPT supplementation under the all-plant protein diet increased FI and digestive enzyme activities in the intestine were partly related to improved neuropeptide Y content and cholecystokinin content, respectively. (2) DMPT supplementation under the all-plant protein diet enhanced the intestinal structural integrity of fish partially by alleviating oxidative damage and partially by up-regulating antioxidant enzyme activities as well as the mRNA levels of antioxidant enzyme (except CuZnSOD), which were partially related to [Keap1a (not Keap1b)/Nrf2] signalling. (3) Finally, based on the quadratic regression analysis for optimal growth performance indices (FI and PWG) and oxidative damage indices (protein carbonyl and malondialdehyde content), the appropriate levels of DMPT supplementation under the all-plant protein diet for on-growing grass carp were estimated as to be 278.30, 282.78, 326.52 and 299.25 mg/kg diet, respectively. In summary, DMPT supplementation under the all-plant protein diet improved the growth performance and digestive capacity and strengthened the intestinal structural integrity of on-growing grass carp. Simultaneously, it also provided a practical and effective approach to the highly efficient utilisation of plant protein and a reference for the non-fish meal diet formulation of fish.

Exogenous Zinc Forms Counteract NaCl-Induced Damage by Regulating the Antioxidant System, Osmotic Adjustment Substances, and Ions in Canola (Brassica napus L. cv. Pactol) Plants

Salinity is the principal natural obstacles for sustainable agriculture, adversely impacting 30% of the world’s irrigated land, resulting in food insecurity, particularly in arid and semi-arid areas. Zinc has several functions in plants; nevertheless, the promising roles of nano-zinc oxide particle in plants under salinity stress are not clear. The current study aims to investigate the roles of zinc (water, 75 mg L−1 zinc sulfate (Zn), and 10 mg L−1 zinc oxide nanoparticle (ZNP)) on the mitigation of NaCl stress (6000 mg L−1) on morpho-physiological attributes and yield of canola plants. Salinity exhibited a substantial reduction in canola plant growth, enhanced photosynthetic pigment degradation, and decreased nutrient concentrations. A decrease in the overall yield and a decrease in various individual components were considerably stimulated by zinc application under non-salinized and salinized conditions. Salinity caused a visible increase in membrane permeability (MP%), malondialdehyde (MDA), and hydrogen peroxide (H2O2) concentrations. Interestingly, zinc application significantly decreased MP%, MDA, and H2O2 concentrations by the upregulation of antioxidant enzymes (superoxide dismutase, catalase, peroxidase) and levels of non-enzymatic antioxidants (ascorbic, carotenoids, and total soluble phenolic compounds). Furthermore, zinc application also enhanced osmoregulation by increasing proline and total soluble carbohydrates accumulation, as well as increased nitrogen, potassium, and phosphorus in the plant tissues in correlation with a decline in sodium and chloride contents. Zinc’s, especially ZNP, role in the mitigation the negative effects of salinity on canola growth and yield may be connected with the upregulating oxidative defense system and osmolyte synthesis as well as ionic regulation.

Upregulation of antioxidant enzymes by organic mineral co-factors to improve oxidative stability and quality attributes of muscle from laying hens

This study investigated the impact of organic trace minerals (OTM: Fe, Cu, Mn, and Zn proteinates premix) and Se-yeast (0.25 mg/kg) as a feed supplement versus inorganic forms of the same minerals (sulfated) on the enzymatic (GPX, CAT, SOD), oxidative, and physicochemical properties of fresh breast muscle from 68-week old hens during storage (4 °C) for 0, 2, 4 and 6 days. OTM with Se-yeast was more effective than sulfated minerals or selenite for enriching meat with Zn, Se and vitamin E (P < .05). At only one-third of the full inorganic mineral supplementation level, OTM with Se-yeast still induced higher GPX activity and greater inhibition of lipid (58% less TBARS) and protein (24% less sulfhydryl loss) oxidation. The organic mineral treatments significantly decreased drip loss and improved color stability of meat when compared with inorganic mineral supplements. Enhanced muscle cellular antioxidant enzymatic activity by the mineral co-factors was plausibly implicated in the protection.

Intermittent Hypoxia Prevents Myocardial Mitochondrial Ca2+ Overload and Cell Death during Ischemia/Reperfusion: The Role of Reactive Oxygen Species.

It has been documented that reactive oxygen species (ROS) contribute to oxidative stress, leading to diseases such as ischemic heart disease. Recently, increasing evidence has indicated that short-term intermittent hypoxia (IH), similar to ischemia preconditioning, could yield cardioprotection. However, the underlying mechanism for the IH-induced cardioprotective effect remains unclear. The aim of this study was to determine whether IH exposure can enhance antioxidant capacity, which contributes to cardioprotection against oxidative stress and ischemia/reperfusion (I/R) injury in cardiomyocytes. Primary rat neonatal cardiomyocytes were cultured in IH condition with an oscillating O2 concentration between 20% and 5% every 30 min. An MTT assay was conducted to examine the cell viability. Annexin V-FITC and SYTOX green fluorescent intensity and caspase 3 activity were detected to analyze the cell death. Fluorescent images for DCFDA, Fura-2, Rhod-2, and TMRM were acquired to analyze the ROS, cytosol Ca2+, mitochondrial Ca2+, and mitochondrial membrane potential, respectively. RT-PCR, immunocytofluorescence staining, and antioxidant activity assay were conducted to detect the expression of antioxidant enzymes. Our results show that IH induced slight increases of O2−· and protected cardiomyocytes against H2O2- and I/R-induced cell death. Moreover, H2O2-induced Ca2+ imbalance and mitochondrial membrane depolarization were attenuated by IH, which also reduced the I/R-induced Ca2+ overload. Furthermore, treatment with IH increased the expression of Cu/Zn SOD and Mn SOD, the total antioxidant capacity, and the activity of catalase. Blockade of the IH-increased ROS production abolished the protective effects of IH on the Ca2+ homeostasis and antioxidant defense capacity. Taken together, our findings suggest that IH protected the cardiomyocytes against H2O2- and I/R-induced oxidative stress and cell death through maintaining Ca2+ homeostasis as well as the mitochondrial membrane potential, and upregulation of antioxidant enzymes.

Lichens of Parmelioid Clade as Promising Multitarget Neuroprotective Agents.

Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease are multifactorial disorders which are increasing in incidence and prevalence over the world without existing effective therapies. The search for new multitarget compounds is the latter therapeutic strategy to address these pathological conditions. Lichens have an important and unknown therapeutic value attributed to their unique secondary metabolites. The aim of this study is to evaluate for the first time the in vitro neuroprotective activities and molecular mechanisms underlying methanol extracts of lichens of the parmelioid clade and to characterize major bioactive secondary metabolites responsible for their pharmacological actions. Of the 15 parmelioid lichen species, our results showed that Parmotrema perlatum and Hypotrachyna formosana methanol extracts exhibited high antioxidant activity as evidenced in ORAC, DPPH, and FRAP assays. Then, SH-SY5Y cells were pretreated with methanol extracts (24 h) followed by Fenton reagent exposure (2 h). Pretreatments with these two more antioxidant methanol lichen extracts increased cell viability, reduced intracellular ROS, prevented oxidative stress biomarkers accumulation, and upregulated antioxidant enzyme (CAT, SOD, GR, and GPx) activity compared to Fenton reagent cells. The neuroprotective activity was much higher for H. formosana than for P. perlatum, even equal to or higher than Trolox (reference compound). Moreover, H. formosana extracts inhibited both AChE and BuChE activities in a concentration dependent manner, and P. perlatum only showed concentration dependent activity against AChE. Finally, chemical composition analysis using TLC and HPLC methods revealed that physodic acid, lividic acid, and lichexanthone are major secondary metabolites in H. formosana and stictic acid and constictic acid are in P. perlatum. These results demonstrated that P. perlatum and, specially, H. formosana are promising multitargeted neuroprotective agents due to their antioxidant and AChE and BuChE inhibition activities.

Cyclohexane, naphthalene, and diesel fuel increase oxidative stress, CYP153, sodA, and recA gene expression in Rhodococcus erythropolis.

In this study, we compared the expression of CYP153, sodA, sodC, and recA genes and ROS generation in hydrocarbon‐degrading Rhodococcus erythropolis in the presence of cyclohexane, naphthalene, and diesel fuel. The expression of cytochrome P450, sodA (encoding Fe/Mn superoxide dismutase), recA, and superoxide anion radical generation rate increased after the addition of all studied hydrocarbons. The peak of CYP153, sodA, and recA gene expression was registered in the presence of naphthalene. The same substrate upregulated the Cu/Zn superoxide dismutase gene, sodC. Cyclohexane generated the highest level of superoxide anion radical production. Hydrogen peroxide accumulated in the medium enriched with diesel fuel. Taken together, hydrocarbon biotransformation leads to oxidative stress and upregulation of antioxidant enzymes and CYP153 genes, and increases DNA reparation levels in R. erythropolis cells.

Potential antigenotoxicity assessment of Ziziphus jujuba fruit

Ziziphus jujuba Mill. fruits are nutritionally rich and have a broad spectrum of health benefits. In this work we hypothesized that this natural product rich in polyphenols might protect humans against DNA damage and its consequences. This has led to our investigation to find out if the fruit extract showed an ability to decrease the frequency of DNA damage (antigenotoxicity) induced by two known genotoxins namely an alkylating agent methyl methane sulphonate (MMS) and a reactive oxygen species (ROS) inducer hydrogen peroxide (H2O2).Human lymphocytes were incubated with the Ziziphus fruit ethanol extracts (ZFE) or betulinic acid (BA) followed by an exposure to either 50 μM of MMS or 250 μM of H2O2. Results suggest that ZFE (250, 500, 1000 μg/ml) and BA (10, 20, 40 μg/ml) were able to inhibit the DNA damaging effect caused by MMS and H2O2 indicative of their protection against the genotoxin. This could be attributed to the interactions of the phenolics, flavonoid and BA present in the fruits.Additional in vivo experiments were carried since BA is an important phytochemical detected in ample amounts in the fruit extract. Mice were primed with BA (2.5, 5.0 and 10 mg/kg body weight) for a period of 6 days. The animals were injected with MMS (10 mg/kg body weight) 24 h later and sacrificed. The genotoxic activity of MMS was inhibited in a dose – related manner by BA. BA reduced the frequency of MMS – induced DNA damage in liver, kidney and bone marrow cells of mice thereby exhibiting its antigenotoxic properties. It could also reduce total glutathione level, lipid peroxidation and hydrogen peroxide content in liver cells of mice through the up-regulation of antioxidant enzymes. Therefore taking into account the antioxidant and antigenotoxic properties, the consumption of the Ziziphus fruit should be more popularized worldwide.

Telmisartan and/or chlorogenic acid attenuates fructose-induced non-alcoholic fatty liver disease in rats: Implications of cross-talk between angiotensin, the sphingosine kinase/sphingoine-1-phosphate pathway, and TLR4 receptors

Renin-angiotensin-aldosterone system (RAS) has been implicated in non-alcoholic fatty liver disease (NAFLD); the most common cause of chronic liver diseases. There is accumulating evidence that altered TLR4 and Sphingosine kinase 1(SphK1)/sphingosine1phosphate (S1P) signaling pathways are key players in the pathogenesis of NAFLD. Cross talk of the sphingosine signaling pathway, toll-4 (TLR4) receptors, and angiotensin II was reported in various tissues. Therefore, the aim of this study was to define the contribution of these two pathways to the hepatoprotective effects of telmisartan and/or chlorogenic acid (CGA) in NAFLD. CGA is a strong antioxidant that was previously reported to inhibit angiotensin converting enzyme. Male Wistar rats were treated with either high-fructose, with or without telmisartan, CGA, telmisartan + CGA for 8 weeks. Untreated NAFL rats showed characteristics of NAFLD, as evidenced by significant increase in the body weight, insulin resistance, and serum hepatotoxicity markers (Alanine and Aspartate transaminases) and lipids as compared to the negative control group, in addition to characteristic histopathological alterations. Treatment with either telmisartan and/or CGA improved aforementioned parameters, in addition to upregulation of antioxidant enzymes (Superoxide dismutase and Glutathione peroxidase). Effect of inhibiting RAS on both sphingosine pathway and TLR4 was evident by the suppressing effect of telmisartan and/or CGA on high fructose-induced upregulation of hepatic SPK1 and S1P, in addition to concomitant up-regulation of Sphingosine-1-Phosphate receptor (S1PR)3 protein level and increased expression of S1PR1 and TLR4. As TLR4 and SPK/S1P signaling pathways play important roles in the progression of liver inflammation, the effect on sphingosine pathway and TLR4 was associated with decreased concentrations of inflammatory markers, enzyme kB kinase (IKK), nuclear factor-kB and tumor necrosis factor-α as compared to untreated NAFL group. In conclusion, the present data strongly suggests the cross-talk between angiotensin, the Sphingosine SPK/S1P Axis and TLR4 Receptors, and their role in the pathogenesis of fructose-induced NAFLD, and the protection afforded by drugs inhibiting RAS.

Salicylic acid alleviates glyphosate-induced oxidative stress in Hordeum vulgare L

Glyphosate (GLY) is considered the most used herbicide in the world and has been associated with several environmental contamination risks. Despite being partially degraded by soil microorganisms, its residues can negatively affect the growth of valuable non-target plants. Thus, there is a need to find new strategies that minimize its impacts and enhance crop tolerance to GLY, allowing a more advantageous and safer, use of this herbicide. Salicylic acid (SA) is a hormone-like substance, able to enhance the efficiency of the antioxidant (AOX) system in plants and their tolerance to oxidative stress. This study aimed to unveil the effects of SA (100 μM) on the oxidative status of Hordeum vulgare L. in response to GLY (30 mg kg−1). After 14 days of growth, the presence of GLY led to a significant inhibition of growth, an accumulation of hydrogen peroxide (H2O2) and superoxide anion (O2-), an increase in lipid peroxidation (LP), proline and non-protein thiols, a decrease of the content of reduced ascorbate (AsA) and an upregulation of AOX enzymes. The exogenous application of SA mitigated the effects of GLY on growth, amount of H2O2 and degree of PL. It has also contributed to the reduction of AsA content, production of non-protein thiols and increased AOX enzymatic activity, particularly superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and gluthatione S-transferase (GST). These results show a positive role of SA against GLY induced oxidative stress, by modulating the AOX capacity of barley plants. However, the observed phytotoxicity of GLY was so pronounced, that the ameliorating effect of SA on AOX defenses was not enough to significantly overcome the herbicide-induced oxidative damage.

Loss of p27kip1 suppresses the myocardial senescence caused by estrogen deficiency.

Estrogen deficiency accelerates the aging process and increases the risk of developing cardiovascular disease (CVD). Apoptosis is one of the important mechanisms of aging. p27kip1 is a cyclin-dependent kinase inhibitor that can regulate cell cycle, apoptosis, and cell motility. p27kip1 overexpression can inhibit cell cycle and increase apoptosis so it has been considered as a marker of aging. In the present study, bilateral ovariectomy (OVX) was performed as a model for menopause in wild-type (WT) and p27kip1 knockout (KO) mice to assess the effects of p27kip1 loss in myocardial aging caused by estrogen deficiency. We found that myocardial fibrosis and heart weight/body weight ratio of mice in the OVX group and p27kip1 KO group were significantly increased. Echocardiography showed that the left ventricular diameter and volume of the WT OVX group increased significantly and the cardiac function decreased. However, there was no significant difference in the results of echocardiography between the two p27kip1 KO groups. The aging and apoptosis indexes in OVX group were increased significantly, However, the indexes in p27kip1 KO mice were decreased. The expression of antioxidant indexes in OVX group was decreased significantly and p27kip1 KO can improve the antioxidant ability. These results provided that estrogen deficiency increased oxidative stress and apoptosis, accelerated aging of heart. p27kip1 KO can partly delay the aging and apoptosis of heart through upregulated antioxidant enzymes.