Mechanism Of Oxidative Damage Research Articles

Protective effect of ginsenoside Rg1 on 661W cells exposed to oxygen-glucose deprivation/reperfusion via keap1/nrf2 pathway.

To construct an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R) induced injury to the optic nerve and to study the oxidative damage mechanism of ischemia-reperfusion (I/R) injury in 661W cells and the protective effect of ginsenoside Rg1. The 661W cells were treated with different concentrations of Na2S2O4 to establish OGD/R model in vitro. Apoptosis, intracellular reactive oxygen species (ROS) levels and superoxide dismutase (SOD) levels were measured at different time points during the reperfusion injury process. The injury model was pretreated with graded concentrations of ginsenoside Rg1. Real-time polymerase chain reaction (PCR) was used to measure the expression levels of cytochrome C (cyt C)/B-cell lymphoma-2 (Bcl2)/Bcl2 associated protein X (Bax), heme oxygenase-1 (HO-1), caspase9, nuclear factor erythroid 2-related factor 2 (nrf2), kelch-like ECH-associated protein 1 (keap1) and other genes. Western blot was used to detect the expression of nrf2, phosphorylated nrf2 (pnrf2) and keap1 protein levels. Compared to the untreated group, the cell activity of 661W cells treated with Na2S2O4 for 6 and 8h decreased (P<0.01). Additionally, the ROS content increased and SOD levels decreased significantly (P<0.01). In contrast, treatment with ginsenoside Rg1 reversed the cell viability and SOD levels in comparison to the Na2S2O4 treated group (P<0.01). Moreover, Rg1 reduced the levels of caspase3, caspase9, and cytC, while increasing the Bcl2/Bax level. These differences were all statistically significant (P<0.05). Western blot analysis showed no significant difference in the protein expression levels of keap1 and nrf2 with Rg1 treatment, however, Rg1 significantly increased the ratio of pnrf2/nrf2 protein expression compared to the Na2S2O4 treated group (P<0.001). The OGD/R process is induced in 661W cells using Na2S2O4. Rg1 inhibits OGD/R-induced oxidative damage and alleviates the extent of apoptosis in 661W cells through the keap1/nrf2 pathway. These results suggest a potential protective effect of Rg1 against retinal I/R injury.

Acrolein Exposure Impaired Glucose Homeostasis and Increased Risk of Type 2 Diabetes: An Urban Adult Population-Based Cohort Study with Repeated Measures

Acrolein is an identified high-priority hazardous air pollutant ubiquitous in daily life and associated with cardiometabolic risk that attracts worldwide attention. However, the etiology role of acrolein exposure in glucose dyshomeostasis and type 2 diabetes (T2D) is unclear. This repeated-measurement prospective cohort study included 3522 urban adults. Urine/blood samples were repeatedly collected for determinations of acrolein metabolites (N-acetyl-S-(3-hydroxypropyl)-l-cysteine, N-acetyl-S-(2-carboxyethyl)-l-cysteine; acrolein exposure biomarkers), glucose homeostasis, and T2D at baseline and a three-year follow-up. We found that each 3-fold increment in acrolein metabolites was cross-sectionally associated with 5.91-6.52% decrement in homeostasis model assessment-insulin sensitivity (HOMA-IS) and 0.07-0.14 mmol/L, 4.02-4.57, 5.91-6.52, 19-20, 18-19, and 23-31% increments in fasting glucose (FPG), fasting insulin (FPI), HOMA-insulin resistance (HOMA-IR), risks of prevalent IR, impaired fasting glucose (IFG), and T2D, respectively; longitudinally, participants with sustained-high acrolein metabolite levels had increased risks of incident IR, IFG, and T2D by 63-80, 87-99, and 120-154%, respectively (P < 0.05). In addition, biomarkers of heme oxygenase-1 activity (exhaled carbon monoxide), lipid peroxidation (8-iso-prostaglandin-F2α), protein carbonylation (protein carbonyls), and oxidative DNA damage (8-hydroxy-deoxyguanosine) mediated 5.00-38.96% of these associations. Our study revealed that acrolein exposure may impair glucose homeostasis and increase T2D risk via mediating mechanisms of heme oxygenase-1 activation, lipid peroxidation, protein carbonylation, and oxidative DNA damage.

New insights into the oxidative damage and antioxidant defense mechanism in Manila clams (Ruditapes philippinarum) exposed to 8:2 polyfluoroalkyl phosphate diester stress

8:2 perfluoroalkyl phosphate diester (8:2 diPAP) is the main precursor of perfluoroalkyl carboxylic acids, and it has been detected in a wide range of environments. In this study, conventional biochemical and histopathological analyses and transcriptome methods were used to investigate the accumulation and oxidative stress of 8:2 diPAP in Manila clams (Ruditapes philippinarum) as well as the clam's defense mechanisms for the first time. The hepatopancreas was the main target organ for 8:2 diPAP accumulation; the concentration reached 484.0 ± 15.5 ng/g after 7 days of exposure to 10 μg/L of 8:2 diPAP, which was 2–100 times higher than that found in other organs. 8:2 diPAP accumulation resulted in significant lipid peroxidation, and the change in malondialdehyde content was highly correlated with 8:2 diPAP accumulation (r > 0.8). The antioxidant enzymes catalase and peroxidase were significantly activated at 7 days of exposure. Although the levels subsequently returned to normal, this restoration was unable to prevent damage. Histopathological analysis showed that 8:2 diPAP exposure resulted in inflammatory damage to the hepatopancreas, which failed to resolve during the recovery period. Transcriptomic analyses showed that the expression of differentially expressed genes had different degrees of positive/negative correlation with antioxidant indicators, and they were significantly enriched in cell death regulatory pathways such as autophagy, apoptosis, and necrosis. The core factor expression results indicated that 8:2 diPAP exposure induced activation of the organismal autophagy factor followed by a shift towards apoptosis. In addition, pathways related to amino acid metabolism and energy metabolism were involved in determining the cell fate of Manila clams. Overall, these results indicated that 8:2 diPAP induced peroxidation of membrane lipids, disturbed physiological processes, and ultimately initiated programmed cell death in Manila clams. The findings of this study provide new insights into the mechanism of toxicity of 8:2 diPAP exposure in marine bivalves.

Mechanism of oxidative damage in Escherichia coli caused by epigallocatechin gallate (EGCG) in the presence of calcium ions

Abstract Tea polyphenols can be developed into new types of disinfectants for drinking water. The antibacterial effect of epigallocatechin gallate (EGCG) on Escherichia coli (E. coli) in the presence of Ca2+ is affected by the Ca2+ concentration. The oxidative damage mechanism and oxidative damage process of EGCG in E. coli under the presence of Ca2+ were deeply analyzed under three aspects: reactive oxygen species (ROS), antioxidant system, and oxidative stress response in E. coli to provide a theoretical basis for the use of EGCG as a disinfectant in drinking water disinfection. EGCG leads to excessive production of superoxide anion in E. coli and the presence of Ca2+ promotes further imbalance of superoxide anion in E. coli; Ca2+ has little effect on EGCG hindering the scavenging of hydroxyl radicals in bacteria; EGCG can hinder the effect of antioxidant enzymes in E. coli, and Ca2+ has a particular regulatory effect on antioxidant enzymes, thus hindering the oxidative damage of EGCG to E. coli; Ca2+ can cause the expression of the oxyR and DPS genes, protect bacterial DNA, and prevent EGCG from damaging bacterial DNA. In the presence of a high concentration of Ca2+, it may activate the cell efflux pump through the soxS gene, resulting in E. coli resistance to EGCG.

Research on synthesis and property of nano-textured Sc2O3-MgO efficient antibacterial agents.

In order to obtain the inorganic efficient antibacterial agents, the means of ion doping and morphology construction in this research are used to enhance the antibacterial property of nano-MgO, which is according to the "oxidative damage mechanism" and "contact mechanism". In this work, the nano-textured Sc2O3-MgO are synthesized by doping Sc3+ in nano-MgO lattice through calcining at 600°C. When the Sc3+ content reaches 10%, the nanotextures on the powders surface are pretty clearly visible and uniform, and the specific surface area and the oxygen vacancy are ideal, so that the 10% Sc3+-doped powders (SM-10) has the excellent antibacterial property against E. coli and S. aureus (MBC = 0.03mg/mL). The efficient antibacterial agents in this research have a better antibacterial effect than the 0% Sc3+-doped powders (SM-0, MBC = 0.20mg/mL) and the commercial nano-MgO (CM, MBC = 0.40mg/mL), which have application prospects in the field of antibacterial.

Activated AMPK-mediated glucose uptake and mitochondrial dysfunction is critically involved in the glutamate-induced oxidative injury in HT22 cell

BackgroundAccumulation of glutamate damages neurons via the reactive oxygen species (ROS) injury, which was involved in the development of neurodegenerative diseases. However, the mechanism of neuronal oxidative stress damage caused by glutamate and the intervention targets still needs to be further studied. This study explored whether 5′ adenosine monophosphate-activated protein kinase (AMPK)-induced glucose metabolic and mitochondrial dysfunction were related to glutamate-dependent ROS injury of the neuron. MethodsNeuronal oxidative stress injury was induced by glutamate treatment in HT-22 cells. Western blotting was used to evaluate the phosphorylation of the AMPK. The XF24 Flux Analyzer was used to measure the effect of glutamate and Compound C (a well-known pharmacological inhibitor of AMPK phosphorylation) on the cellular oxygen consumption rate (OCR) of HT-22 cells. Glucose uptake, intracellular ROS, mitochondrial potential, apoptosis and cell viability were quantified using biochemical assays. ResultsGlutamate caused the phosphorylation of AMPK and subsequently promoted the glucose uptake. Furthermore, AMPK-mediated glucose uptake enhanced OCR and increased the intracellular ROS levels in neurons. The pharmacological inhibition of AMPK phosphorylation by Compound C attenuated glutamate-induced toxicity in HT22 cells by regulating the glucose uptake/mitochondrial respiration/ROS pathway. ConclusionsThe AMPK phosphorylation/glucose uptake/mitochondrial respiration/ROS pathway was involved in glutamate-induced excitotoxic injury in HT22 cells. The inhibition of AMPK phosphorylation may be a potential target for the development of therapeutic agents for treating the glutamate-induced neurotoxicity.

Oxidative Stress in Assisted Reproductive Techniques, with a Focus on an Underestimated Risk Factor.

Based on current findings, the presence of oxidative stress has a significant impact on the quality of gametes and embryos when performing assisted reproductive techniques (ART). Unfortunately, in vitro manipulation of these cells exposes them to a higher level of reactive oxygen species (ROS). The primary goal of this review is to provide a comprehensive overview of the development of oxidative stress in female and male reproductive systems, as well as in the case of the pre-implantation embryo and its environment. This review also focuses on the origins of ROS and the mechanisms of oxidative stress-induced damage during ART procedures. A well-known but underestimated hazard, light exposure-related photo-oxidation, is particularly concerning. The effect of oxidative stress on ART outcomes, as well as the various strategies for preventing it, are also discussed. We emphasize the role and significance of antioxidants and light protection including forms, functions, and mechanisms in the development of gametes and embryos in vivo and in vitro.

A Proteome-Centric View of Ageing, including that of the Skin and Age-Related Diseases: Considerations of a Common Cause and Common Preventative and Curative Interventions.

The proteome comprises all proteins of a cell or organism. To carry their catalytic and structure-related functions, proteins must be correctly folded into their unique native three-dimensional structures. Common oxidative protein damage affects their functionality by impairing their catalytic and interactive specificities. Oxidative damage occurs preferentially to misfolded proteins and fixes the misfolded state. This review provides an overview of the mechanism and consequences of oxidative proteome damage - specifically irreversible protein carbonylation - in relation to ageing, including that of the skin as well as to age-related degeneration and diseases (ARDD) and their mitigation. A literature review of published manuscripts, available from PubMed, focusing on proteome, proteostasis, proteotoxicity, protein carbonylation, related inflammatory diseases, ARDD and the impact of the damaged proteome on ageing. During ageing, proteome damage, especially protein carbonylation, correlates with biological age. Carbonylated proteins form aggregates which can be considered as markers and accelerators of ageing and are common markers of most ARDD. Protein carbonylation leads to general ageing of the organism and organs including the skin and potentially to diseases including Alzheimer and Parkinson disease, diabetes, psoriasis, and skin cancer. Current research is promising and may open new therapeutic approaches and perspectives by targeting proteome protection as an age and ARDD management strategy.

The Role and Mechanism of Polysaccharides in Anti-Aging.

The elderly proportion of the population is gradually increasing, which poses a great burden to society, the economy, and the medical field. Aging is a physiological process involving multiple organs and numerous reactions, and therefore it is not easily explained or defined. At present, a growing number of studies are focused on the mechanisms of aging and potential strategies to delay aging. Some clinical drugs have been demonstrated to have anti-aging effects; however, many still have deficits with respect to safety and long-term use. Polysaccharides are natural and efficient biological macromolecules that act as antioxidants, anti-inflammatories, and immune regulators. Not surprisingly, these molecules have recently gained attention for their potential use in anti-aging therapies. In fact, multiple polysaccharides have been found to have excellent anti-aging effects in different animal models including Caenorhabditis elegans, Drosophila melanogaster, and mice. The anti-aging qualities of polysaccharides have been linked to several mechanisms, such as improved antioxidant capacity, regulation of age-related gene expression, and improved immune function. Here, we summarize the current findings from research related to anti-aging polysaccharides based on various models, with a focus on the main anti-aging mechanisms of oxidative damage, age-related genes and pathways, immune modulation, and telomere attrition. This review aims to provide a reference for further research on anti-aging polysaccharides.

Evolution of microstructure and mechanical properties of Cf/SiC-Al composites after high-temperature oxidation

The evolution of micro-morphology and physical properties of Cf/SiC-Al composites prepared by precursor impregnation and pyrolysis (PIP) and high-temperature pressure infiltration processes after high-temperature oxidation (300–700 °C) was investigated. Nanoindentation method was used to characterize the hardness and elastic modulus of each component of the composites. The results demonstrated that with the increased of the oxidation temperature, the weight loss rate of the composites gradually increased, and in-plane compressive strength decreases gradually. The composites showed significant oxidation damage after the oxidation temperature exceeded 500 °C, and the nanoindentation hardness and elastic modulus of the Al alloy matrix were significantly reduced. After the oxidation treatment at 700 °C, the Al alloy matrix in the composites even melted and flowed out. The oxidative damage and compression fracture failure mechanisms of the composites after oxidation were also further discussed and analyzed.

Superoxide Release by Macrophages through NADPH Oxidase Activation Dominating Chemistry by Isoprene Secondary Organic Aerosols and Quinones to Cause Oxidative Damage on Membranes.

Oxidative stress mediated by reactive oxygen species (ROS) is a key process for adverse aerosol health effects. Secondary organic aerosols (SOA) account for a major fraction of fine particulate matter, and their inhalation and deposition into the respiratory tract causes the formation of ROS by chemical and cellular processes, but their relative contributions are hardly quantified and their link to oxidative stress remains uncertain. Here, we quantified cellular and chemical superoxide generation by 9,10-phenanthrenequinone (PQN) and isoprene SOA using a chemiluminescence assay combined with electron paramagnetic resonance spectroscopy as well as kinetic modeling. We also applied cellular imaging techniques to study the cellular mechanism of superoxide release and oxidative damage on cell membranes. We show that PQN and isoprene SOA activate NADPH oxidase in macrophages to release massive amounts of superoxide, overwhelming the superoxide formation by aqueous chemical reactions in the epithelial lining fluid. The activation dose for PQN is 2 orders of magnitude lower than that of isoprene SOA, suggesting that quinones are more toxic. While higher exposures trigger cellular antioxidant response elements, the released ROS induce oxidative damage to the cell membrane through lipid peroxidation. Such mechanistic and quantitative understandings provide a basis for further elucidation of adverse health effects and oxidative stress by fine particulate matter.

Myricetin-Loaded Nanomicelles Protect against Cisplatin-Induced Acute Kidney Injury by Inhibiting the DNA Damage-cGAS-STING Signaling Pathway.

Acute kidney injury (AKI) is the most common side effect of the anti-cancer drug cisplatin, and currently, no effective preventive measures are available in clinical practice. Oxidative stress and DNA damage mechanisms may be involved in cisplatin-induced AKI. In this study, we prepared Kolliphor HS15-based myricetin-loaded (HS15-Myr) nanomicelles and explored the mechanism of protection against cisplatin-induced AKI. In vitro results showed that the HS15-Myr nanomicelles enhanced the antioxidant activity of myricetin (Myr) and inhibited cisplatin-induced proliferation inhibition of HK-2 cells. Moreover, the HS15-Myr nanomicelles inhibited cisplatin-induced reactive oxygen species accumulation, mitochondrial membrane potential reduction, and DNA damage, which might be related to the inhibition of the cyclic GMP-AMP synthase (cGAS)─stimulating interferon gene (STING) signaling pathway. In vivo results in mice showed that the significant reductions in body weight and renal indices and the increased blood urea nitrogen and serum creatinine levels induced by cisplatin could be significantly reversed by pretreating with the HS15-Myr nanomicelles. Furthermore, nanomicelle pretreatment significantly altered the activities of antioxidant enzymes (e.g., GSH, MDA, and SOD) induced by cisplatin. In addition, cisplatin-induced inflammatory responses in mouse kidney tissue were found to be inhibited by pretreatment with HS15-Myr nanomicelles, such as IL-1β and TNF-α expression. The nanomicelles also significantly inhibited cisplatin-induced activation of the DNA damage-cGAS-STING pathway in kidney tissues. Together, our findings suggest that Myr-loaded nanomicelles are potential nephroprotective drugs.

Effects of aniline on growth, oxidative and DNA damage of rice (Oryza sativa L.) seedlings

Aniline is widely used in the fields of industry and agriculture. Aniline pollution is emerging as a serious global environmental problem, whereas the toxicity and the stress mechanism on higher plants is unclear. In order to clarify the mechanism of growth, oxidative and DNA damage caused by aniline in higher plants, we cultured two varieties of rice in different concentration of aniline solution. The results demonstrated that the germination rate, amylase activity and lipase activity were significantly inhibited during the germination period of rice when aniline concentration was ≥ 25 mg L −1 ( p < 0.05 or p < 0.01). Besides, aniline also significantly inhibited the growth of rice seedlings, especially the growth of root. In comparison with the control group, the length of rice root was reduced by 17.27%–76.26% (Mudanjiang 25) and 21.20%–77.36% (Yunxian 510). The accumulation trends of . O 2 − (superoxide anion), H 2 O 2 (hydrogen peroxide), and MDA (malondialdehyde) in the two rice were increased continuously, the antioxidant enzyme activity was first increased and then decreased. When the aniline concentration was higher than 50 mg L −1 , the enzyme activity decreased rapidly (especially for Yunxian 510). Furthermore, the DNA hyperchromicity effect increased first and then decreased, which indicated that low-concentrations aniline might induce DNA breakage and high-concentrations aniline might promote the occurrence of cross-linking of DNA chains. Aniline could reduce the DNA content of the two varieties of rice shoots and roots. Especially for Yunxian 510, the DNA content of leaves and roots respective was decreased by 69.37% and 81.19% when the aniline was 200 mg L −1 , which was significantly lower than that of Mudanjiang 25 ( p < 0.01). These results evidently demonstrate that aniline maintain serious growth, oxidative, and genetic toxic effects on rice, and the Yunxian 510 was more sensitive to aniline poisoning than that of Mudanjiang 25. • Aniline had a phytotoxic–genotoxic effect on the rice growth process. • Aniline significantly inhibited rice amylase and lipase activities at concentrations >10 mg L {-1} . • Aniline significantly inhibited rice germination and growth at concentrations >25 mg L {-1} . • Aniline above 50 mg L {-1} inhibited the activity of antioxidant enzymes, resulting in increased content of ROS in rice. • Aniline lead to an increase in the degree of DNA cross-linking and a decrease in DNA content in rice.

Elucidation of the potential antioxidant compound and mechanism of mung bean using network pharmacology and in vitro anti-oxidative activity

Mung bean is rich in bioactive components, but the main compound and pharmacological mechanism in reducing oxidative and free radical damage are unclear. Network pharmacology and 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical scavenging activities were employed to uncover the antioxidant mechanism of potentially active compounds, considering the interactions between mung bean targets and oxidative and free radical damage. These key targets were analyzed by protein–protein interactions (PPIs), and key genes were used to find the biological pathway and therapeutic mechanism by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The results showed that five antioxidant components and 18 mung bean targets were screened. β-carotene and vitexin both played a crucial role in mung bean against oxidative and free radical damage, and the ABTS radical scavenging activities of β-carotene and vitexin were 94.84 and 87.79%, which were equivalent to those of vitamin C. Key targets may be AR, HSP90AA1, MYC, and CASP3 for mung bean to exert antioxidant activity. GO and KEGG indicated that mung bean may mainly act on thyroid hormone signaling pathway, estrogen signaling pathway, p53 signaling pathway, etc. In vitro antioxidant activity tests showed that the bioactive ingredients of mung beans had great antioxidant activity. Network pharmacology analysis also revealed the underlying molecular mechanisms of oxidative and free radical damage. This study provides new insights and evidence to explore the bioactive compounds and biological functions of food cereals and legumes, as well as a reference for the functional evaluation of food ingredients and the development of functional foods.

Investigation of oxidative damage, antioxidant balance, DNA repair genes, and apoptosis due to radiofrequency-induced adaptive response in mice

ABSTRACT This study aims to determine whether exposure to non-ionizing radiofrequency fields could induce an adaptive response (AR) in adult mice and to reveal potential molecular mechanisms triggered by RF-induced AR. The study was performed on 24 adult male Swiss-Albino mice. The average mass of the mice was 37 g. Four groups of adult mice, each consisting of 6, were formed. The radiofrequency group (R) and the adaptive response group (RB) were exposed to 900 MHz of global system for mobile communications (GSM) signal at 0.339 W/kg (1 g average specific absorption rate) 4 h/day for 7 days, while the control group (C) and the bleomycin group (B) were not exposed. 20 minutes after the last radiofrequency field (RF) exposure, the mice in the B and RB groups were injected intraperitoneal (ip) bleomycin (BLM), 37.5 mg/kg. All the animals were sacrificed 30 minutes after the BLM injection. Oxidative damage and antioxidant mechanism were subsequently investigated in the blood samples. Changes in the expression of the genes involved in DNA repair were detected in the liver tissue. TUNEL method was used to determine the apoptosis developed by DNA fragmentation in the liver tissue. The RB group, which produced an adaptive response, was compared with the control group. According to the results, the increase of reactive oxygen species (ROS) in the RB group may have played an important role in triggering the adaptive response and producing the required minimum stress level. Furthermore, tumor suppressor 53(p53), oxo guanine DNA glycosylase (OGG-1) levels responsible for DNA repair mechanism genes expression were increased in conjunction with the increase in ROS. The change in the poly (ADP-ribose) polymerase 1 (PARP-1) and glutathione peroxidase 1 (GPx-1) gene expression were not statistically significant. The antioxidant enzyme levels of superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC) were decreased in the group with adaptive response. According to the data obtained from terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis, apoptosis was decreased in the RB group due to the decrease in cell death, which might have resulted from an increase in gene expression responsible for DNA repair mechanisms. The results of our study show that exposure to RF radiation may create a protective reaction against the bleomycin. The minimal oxidative stress due to the RF exposure leads to an adaptive response in the genes that play a role in the DNA repair mechanism and enzymes, enabling the survival of the cell.

Scrutinizing the interaction between metribuzin with glutathione reductase 2 from Arabidopsis thaliana: insight into the molecular toxicity in agriculture.

As one of the triazine herbicides with widespread usage in agriculture, metribuzin exerted nonnegligible hazardous effects on plants via excessive accumulation of reactive oxygen species and destruction of antioxidant enzymes, but the underlying harmful mechanism of metribuzin-induced oxidative damage to plants has never been exploited. Here, Arabidopsis thaliana glutathione reductase 2 (AtGR2) was employed as the biomarker to evaluate the adverse impacts of metribuzin on plants. The fluorescence intensity of AtGR2 was decreased based on the static quenching mechanism with the prediction of a single binding site toward metribuzin, and the complex formation was presumed to be mainly impelled by hydrogen bonding and van der Waals forces from the negative ΔH and ΔS. In addition, the loosened and unfolded skeleton of AtGR2 along with the increased hydrophilicity around the tryptophan residues were investigated. Besides, the glutathione reductase activity of AtGR2 was also destroyed due to structural and conformational changes. At last, the severe inhibiting growth of Arabidopsis seedling roots was discovered under metribuzin exposure. Hence, the evaluation of the molecular interaction mechanism of AtGR2 with metribuzin will establish valuable assessments of the toxic effects of metribuzin on plants.

OXR1 signaling pathway as a possible mechanism of elastase-induced oxidative damage in pulmonary cells: the protective role of ellagic acid.

Oxidative stress is a process that occurs through free radicals on the cell membranes which causes damage to the cell and intracellular organelles, especially mitochondria membranes. H2O2 induced oxidative stress in human cells is of interest in toxicological research since oxidative stress plays a main role in the etiology of several pathological conditions. Neutrophil Elastase (Serine proteinase) is involved in the pathology process of emphysema as a respiratory disease through lung inflammation, and destruction of alveolar walls. The present study investigated the direct oxidative stress effects of Elastase in comparison with H2O2 on human lung epithelial cells (A549 cells) concerning the generation of reactive oxygen species (ROS) and modulation of oxidation resistance 1 (OXR1) and its downstream pathway using the well-known antioxidant Ellagic acid as an activator of antioxidant genes. The human pulmonary epithelial cells (A549) were divided into the nine groups including Negative control, Positive control (H2O2), Elastase (15, 30, and 60mU/mL), Ellagic acid (10μmol/L), and Elastase + Ellagic acid. Cytotoxicity, ROS generation, oxidative stress profile, level of reactive metabolites, and gene expression of OXR1 and its downstream genes were measured in all groups. The obtained data demonstrated that Elastase exposure caused oxidative stress damage in a dose-depended manner which was associated with decreases in antioxidant defense system genes. Conversely, treatment with Ellagic acid as a potent antioxidant showed improved antioxidant enzyme activity and content which was in line with the upregulation of OXR1 signaling pathway genes. The present findings can highlight the novel mechanism underlying the oxidative stress induced by Neutrophil Elastase through OXR1 and related genes. Moreover, the benefit of Ellagic acid on cytoprotection, resulting from its antioxidant properties was documented.

The main side effects of statins in clinical practice

Statins have long occupied a central place in cardiovascular medicine, being an integral component of the prevention and treatment of atherosclerotic cardiovascular diseases (coronary heart disease and its main clinical forms, angina pectoris and myocardial infarction; transient ischemic attacks, ischemic strokes, etc.). By blocking a key enzyme of cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA-reductase), statins normalize the parameters of the lipid spectrum, primarily, the serum levels of atherogenic low-density lipoprotein cholesterol. However, in addition to the beneficial effects of statins, side effects are also characteristic, which are a significant problem in modern clinical practice due to the fact that they can cause dangerous disorders, forcing physicians to reduce dosages or completely cancel these drugs. Understanding the side effects and the mechanisms underlying their formation is important for improving the measures for the early detection, prevention and treatment of those disorders. This article discusses such side effects of statins as myotoxicity, hepatotoxicity, nephrotoxicity. The pathogenetic mechanisms underlying these toxic effects of statins are discussed. A particular attention is paid to the effect of statins on the oxidative stress, the mechanisms of oxidative damage to cellular macromolecules (lipids, proteins and DNA) and their potential role in the development of myotoxicity, hepatotoxicity and nephrotoxicity.

Oxidative Stress-Induced Damage to the Developing Hippocampus Is Mediated by GSK3β.

Neonatal brain injury renders the developing brain vulnerable to oxidative stress, leading to cognitive deficit. However, oxidative stress-induced damage to hippocampal circuits and the mechanisms underlying long-term changes in memory and learning are poorly understood. We used high oxygen tension or hyperoxia (HO) in neonatal mice of both sexes to investigate the role of oxidative stress in hippocampal damage. Perinatal HO induces reactive oxygen species and cell death, together with reduced interneuron maturation, inhibitory postsynaptic currents, and dentate progenitor proliferation. Postinjury interneuron stimulation surprisingly improved inhibitory activity and memory tasks, indicating reversibility. With decreased hippocampal levels of Wnt signaling components and somatostatin, HO aberrantly activated glycogen synthase kinase 3 β activity. Pharmacological inhibition or ablation of interneuron glycogen synthase kinase 3 β during HO challenge restored progenitor cell proliferation, interneuron development, inhibitory/excitatory balance, as well as hippocampal-dependent behavior. Biochemical targeting of interneuron function may benefit learning deficits caused by oxidative damage.SIGNIFICANCE STATEMENT Premature infants are especially vulnerable to oxidative stress, as their antioxidant defenses are underdeveloped. Indeed, high oxygen tension is associated with poor neurologic outcomes. Because of its sustained postnatal development and role in learning and memory, the hippocampus is especially vulnerable to oxidative damage in premature infants. However, the role of oxidative stress in the developing hippocampus has yet to be explored. With ever-rising rates of neonatal brain injury and no universally viable approach to maximize functional recovery, a better understanding of the mechanisms underlying neonatal brain injury is needed. Addressing this need, this study uses perinatal hyperoxia to study cognitive deficits, pathophysiology, and molecular mechanisms of oxidative damage in the developing hippocampus.

Transcriptome Revealed Exposure to the Environmental Ammonia Induced Oxidative Stress and Inflammatory Injury in Spleen of Fattening Pigs.

Ammonia is one of the major environmental pollutants that seriously threaten human health. Although many studies have shown that ammonia causes oxidative stress and inflammation in spleen tissue, the mechanism of action is still unclear. In this study, the ammonia poisoning model of fattening pigs was successfully established. We examined the morphological changes and antioxidant functions of fattening pig spleen after 30-day exposure to ammonia. Effects of ammonia in the fattening pig spleen were analyzed from the perspective of oxidative stress, inflammation, and histone methylation via transcriptome sequencing technology (RNA-seq) and real-time quantitative PCR validation (qRT-PCR). We obtained 340 differential expression genes (DEGs) by RNA-seq. Compared with the control group, 244 genes were significantly upregulated, and 96 genes were significantly downregulated in the ammonia gas group. Some genes in Gene Ontology (GO) terms were verified and showed significant differences by qRT-PCR. The KEGG pathway revealed significant changes in the MAPK signaling pathway, which is strongly associated with inflammatory injury. To sum up, the results indicated that ammonia induces oxidative stress in pig spleen, activates the MAPK signaling pathway, and causes spleen necrosis and injury. In addition, some differential genes encoding epigenetic factors were found, which may be involved in the response mechanism of spleen tissue oxidative damage. The present study provides a transcriptome database of ammonia-induced spleen poisoning, providing a reference for risk assessment and comparative medicine of ammonia.