Antioxidant Defense System Of Cells Research Articles

Redox Status and Protein Glutathionylation in Binase-Treated HPV16-Positive SiHa Carcinoma Cells

Human papillomavirus type 16 (HPV16) belongs to viruses of the high-risk type and is associated by overexpression of E6 and E7 oncoproteins, which determine the oncogenic properties of the virus, such as immortalization and malignant transformation of proliferating epithelial cells. The biogenesis of redox-sensitive proteins E6 and E7 at the early stages of viral infection leads to blocking of the cell antioxidant defense system and ubiquintin-dependent degradation of p53 and Rb tumor suppressors. Maintaining high rates of tumor cell proliferation contributes to an increase in the level of reactive oxygen species (ROS) and a shift in the redox balance towards oxidative processes. Reduced glutathione (GSH) provides antioxidant protection to tumor cells through S-glutathionylation of thiol groups of redox-sensitive proteins, which leads to the appearance of multidrug-resistant forms of cancer. In this regard, drugs restoring redox balance and increasing susceptibility to antitumor therapy are of particular importance. We have established that, Bacillus pumilus RNase (binase) modulates the redox-dependent regulatory mechanisms that ensure tumor cell resistance to apoptosis in HPV-16-positive SiHa cells of cervical squamous cell carcinoma,. Binase in nontoxic concentrations initiates a number of pre-apoptogenic changes, i.e., decreases ROS and reduced glutathione (GSH) levels, suppresses the expression of the E6 oncoprotein, activates the expression of the p53 tumor suppressor, and reduces the mitochondrial potential of tumor cells. Binase-induced disruption of the integrity of the mitochondrial membrane is a signal for activation of the mitochondrial apoptosis pathway.

Comparison of preoperative and postoperative serum thiol/disulfide levels in patients undergoing laparoscopic sleeve gastrectomy for morbid obesity.

Obesity, a prevalent chronic disease, results from an imbalance between energy intake and expenditure. The oxidative stress associated with obesity stems from an imbalance between reactive oxygen species and the cell's antioxidant defense system. Oxidative stress can cause many diseases. The assessment of thiol/disulfide balance, a biochemical test, can be used to detect oxidative stress. The aim of this study is to determine the changes in oxidative stress associated with obesity after obesity surgery by assessing the thiol/disulfide levels. The study was conducted with 40 volunteer patients with a body mass index (BMI) above 40 who underwent obesity surgery at Harran University Hospital General Surgery. Thiol and disulfide levels and other blood parameters were measured from the preoperative and postoperative 2nd and 6th-month blood samples of the patients. BMI was calculated by recording the weights and heights of the cases. Patients with diseases that could affect oxidative stress measurements and those using medication were excluded from the study, and the analyses were performed accordingly. The results showed a statistically significant decrease in native thiol, disulfide, reduced thiol, oxidized thiol, glucose, ALT (alanine aminotransferase), ALP (alkaline phosphatase), total cholesterol, HDL (high-density lipoprotein), triglyceride, and BMI values between the preoperative, 2-month postoperative, and 6-month postoperative measurements (p<0.05). Restrictive methods such as sleeve gastrectomy in individuals with morbid obesity led to weight control and a decrease in adipose tissue, reducing oxidative stress and increasing antioxidant response.

Antioxidant Potentials and other Biological Activities of Protium heptaphyllum (Aubl.). March: Mini-Review

Background: Oxidative stress occurs when the cell's antioxidant defense system is insufficient. This can be corrected by active antioxidant substances, which help to eliminate the consequences of the damage caused or prevent the system from reaching the stress level. Objective: The actions of antioxidants can inhibit or delay tumor cells' appearance, delaying aging, and preventing other cellular damage resulting from the redox imbalance. Therefore, the present work aimed to research studies already published on Protium heptaphyllum (P. heptaphyllum) and its biological activities, mainly antioxidant effects once resulting from phenolic compounds, such as flavonoids, present in the plant. Methods: The methodology used was a literature review where information was collected from several studies related to P. heptaphyllum, oxidative stress, polyphenols, and flavonoids in databases, such as Scielo, PubMed, Google Scholar, LILACS, Chemical Abstract, ScienceDirect, among others in the period from 2002 to 2021. Results: The main studies carried out with metabolites of P. heptaphyllum demonstrated several biological activities such as antioxidant, gastroprotective, anti-inflammatory, analgesic, anxiolytic, antihyperglycemic, hyperlipidemic, among others. Although P. heptaphyllum has been little investigated by pharmacological studies, the results reported in this work may contribute to this plant species' chemical/ pharmacological knowledge. Therefore, the secondary metabolites present in the plant may become test targets in future clinical trials for the drug arsenal. Conclusion: It can be observed that P. heptaphyllum is a promising source of secondary compounds, mainly flavonoids.

CISPLATIN - AN OVERVIEW OF ITS EFFICIENCY AND TOXICITY

Cisplatin is the first heavy metal compound that has been found to possess antineoplastic activity. It is effective in treating testicular, ovarian, head and neck, bladder, cervical, esophageal tumors, and small cell lung carcinoma. Approximately 1% of cisplatin that enters the cell interacts with DNA, forming DNA-cisplatin bonds. Both apoptosis and necrosis can be found in the same population of cells exposed to cisplatin, and the mode of cell death depends on the cisplatin concentration and metabolic state of the target cell. In the bloodstream, the platinum component of cisplatin binds to the blood's proteins (hemoglobin, albumin and transferrin), and other significant portion binds to the glutathione and other cysteine-rich biomolecules. Cisplatin impairs the mitochondrial and cell antioxidant defense system (decreases GSH, NADPH levels, GCH/GSSG ratio, and increases GSSG levels) leading to oxidative stress. There are three main mechanisms of cell resistance to cisplatin: (1) enhanced repair of cisplatin-induced DNA lesions, (2) decrease in uptake and/or increase in efflux and (3) inactivation of cisplatin intracellularly. The usage of cisplatin is limited due to its toxicity and side effects, which include neurotoxicity (numbness and tingling, paresthesia, reduced deep tendon reflexes), nephrotoxicity (renal insufficiency, hypomagnesemia), ototoxicity (tinnitus and bilateral high-frequency hearing loss), cardiotoxicity (changes in electric heart activity, congestive heart failure), gastrotoxicity (nausea, vomiting, and dyspepsia), etc. So far, there has been no effective, clinically administered, therapy for cisplatin-induced toxicity.

Repetitive Cerulein-Induced Chronic Pancreatitis in Growing Pigs-A Pilot Study.

Chronic pancreatitis (CP) is an irreversible and progressive inflammatory disease. Knowledge on the development and progression of CP is limited. The goal of the study was to define the serum profile of pro-inflammatory cytokines and the cell antioxidant defense system (superoxidase dismutase-SOD, and reduced glutathione-GSH) over time in a cerulein-induced CP model and explore the impact of these changes on selected cytokines in the intestinal mucosa and pancreatic tissue, as well as on selected serum biochemical parameters. The mRNA expression of CLDN1 and CDH1 genes, and levels of Claudin-1 and E-cadherin, proteins of gut barrier, in the intestinal mucosa were determined via western blot analysis. The study showed moderate pathomorphological changes in the pigs' pancreas 43 days after the last cerulein injection. Blood serum levels of interleukin (IL)-1-beta, IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGTP), SOD and GSH were increased following cerulein injections. IL-1-beta, IL-6, TNF-alpha and GSH were also increased in jejunal mucosa and pancreatic tissue. In duodenum, decreased mRNA expression of CDH1 and level of E-cadherin and increased D-lactate, an indicator of leaky gut, indicating an inflammatory state, were observed. Based on the current results, we can conclude that repetitive cerulein injections in growing pigs not only led to CP over time, but also induced inflammation in the intestine. As a result of the inflammation, the intestinal barrier was impaired.

Foliar application of putrescine, salicylic acid, and ascorbic acid mitigates frost stress damage in Vitis vinifera cv. ‘Giziluzum’

BackgroundCold stress is an effective factor in reducing production and injuring fruit trees. Various materials, such as salicylic acid, ascorbic acid, and putrescine, are used to alleviate the damage of abiotic stress.ResultsThe effect of different treatments of putrescine, salicylic acid, and ascorbic acid on alleviating the damage of frost stress (− 3 °C) to grapes ‘Giziluzum’ was investigated. Frost stress increased the amount of H2O2, MDA, proline, and MSI. On the other hand, it decreased the concentration of chlorophyll and carotenoids in the leaves. Putrescine, salicylic acid and ascorbic acid significantly increased the activities of catalase, guaiacol peroxidase, ascorbate peroxidase, and superoxide dismutase under frost stress. Following frost stress, the grapes treated with putrescine, salicylic acid, and ascorbic acid showed higher levels of DHA, AsA, and AsA/DHA than the untreated grapes. Our results showed that the treatment with ascorbic acid outperformed the other treatments in adjusting frost stress damages.ConclusionThe use of compounds, such as ascorbic ac id, salicylic acid, and putrescine, modulates the effects of frost stress, thereby increasing the antioxidant defense system of cells, reducing its damage, and stabilizing stable cell conditions, so it can be used to reduce frost damage to different grape cultivars.

Nano-silicon mediated alleviation of Cd toxicity by cell wall adsorption and antioxidant defense system in rice seedlings

Nano-silicon mediated alleviation of Cd toxicity by cell wall adsorption and antioxidant defense system in rice seedlings

Mechanisms associated with the dysregulation of mitochondrial function due to lead exposure and possible implications on the development of Alzheimer's disease.

Lead (Pb) is a multimedia contaminant with various pathophysiological consequences, including cognitive decline and neural abnormalities. Recent findings have reported an association of Pb toxicity with Alzheimer's disease (AD). Studies have revealed that mitochondrial dysfunction is a pathological characteristic of AD. According to toxicology reports, Pb promotes mitochondrial oxidative stress by lowering complex III activity in the electron transport chain, boosting reactive oxygen species formation, and reducing the cell's antioxidant defence system. Here, we review recent advances in the role of mitochondria in Pb-induced AD pathology, as well as the mechanisms associated with the mitochondrial dysfunction, such as the depolarisation of the mitochondrial membrane potential, mitochondrial permeability transition pore opening; mitochondrial biogenesis, bioenergetics and mitochondrial dynamics alterations; and mitophagy and apoptosis. We also discuss possible therapeutic options for mitochondrial-targeted neurodegenerative disease (AD).

Formulation and Evaluation of Kaempferol Loaded Nanoparticles against Experimentally Induced Hepatocellular Carcinoma: In Vitro and In Vivo Studies.

The present study was designed to prepare Kaempferol loaded nanoparticles (KFP-Np) and evaluate hepatoprotective and antioxidant effects in hepatocellular carcinoma models. KFP was encapsulated with hydroxypropyl methylcellulose acetate succinate (HPMC-AS) and Kollicoat MAE 30 DP polymers to prepare nanoparticles (Nps) by quasi-emulsion solvent diffusion technique (QESD). The prepared Nps were evaluated for different pharmaceutical characterization to select the optimum composition for the in vivo assessment. An animal model of cadmium chloride (CdCl2)-induced hepatocellular carcinoma in Male Sprague Dawley rats was used in vivo to test the antioxidant and hepatoprotective capacity of free and encapsulated KFP. The prepared Npsshowed nanometric size, low PDI, high drug load as well as encapsulation with a better drug release profile. There was a significant decrease in the increased serum levels of alanine transaminase (ALT), total bilirubin (TBiL), and aspartate transaminase (AST), and the lipid peroxidation’s (MDA) level was attenuated, and levels of markers of the cell antioxidant defence system were restored including Glutathione S-transferase (GST), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) via oral pre-treatment with KFP-Np (50 mg/kg b.w. (body weight), 6 weeks). KFP-Np significantly declines an mRNA expression of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) as well as decreased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein expression. It also upregulated the mRNA expression and protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). While comparing the protective effects of KFP encapsulated in Kollicoat MAE 30 DP and HPMC-AS, Nps was found to be betterthan free KFP. Insummary, result indicate that encapsulation of KFP in NPs provides a potential platform for oxidative stress induce liver injury.

Boron-toxicity induced changes in cell wall components, boron forms, and antioxidant defense system in rice seedlings

Boron (B) is an indispensable micronutrient that ensures the optimal growth and productivity of the plant. However, excessive use of B fertilizers results in B toxicity which is relatively difficult to correct as compared to B deficiency. Moreover, underlying mechanisms of B toxicity induced changes in cell wall components and the association of B forms in the appearance of toxicity symptoms in rice seedlings are lacking. Therefore, the present investigation was carried out on rice seedlings by employing different concentrations of B (CK, B1; 100 µM, B2; 300 µM, and B3; 400 µM). The results showed that a high concentration of B caused inhibition of root and shoot growth with noticeable signs of stress on leaves in terms of chlorophyll contents. In addition, B toxicity caused oxidative stress and lipid oxidation of membranes. The higher concentrations of B were accumulated in the leaves than roots. In the roots and leaves, more than 80% B was adsorbed on the cell wall. In the treatment of B3, the free form of B was higher than the bound-B. Fourier Transform Infrared Spectrometer (FTIR) results showed that higher concentrations led to variation in functional groups of cell walls of leaves. The results of this investigation showed that B stress-induced inhibition of growth might be linked with higher B uptake in the upper parts, oxidative damages, and forms of B may play important role in the chlorosis. The findings of the study may help to understand the mechanisms of B stress-induced growth inhibition in rice seedlings.

Inhibitory effect and mechanism of three macrophytes extract on Microcystis aeruginosa growth and physiology

AbstractMacrophytes are a promising source of bioactive compounds with potential applications in the biocontrol of harmful cyanobacteria blooms. In this study, we investigated the inhibitory effects of extracts from three macrophytes (Nasturtium officinale, Potamogeton natans and Ranunculus aquatilis) on Microcystis aeruginosa. We assessed physiological indicators of inhibition on M. aeruginosa, including lipid peroxidation, protein content, superoxide dismutase activity, catalase activity and growth. The chemical composition of the macrophyte extracts and their specific allelochemicals were analysed using high‐performance liquid chromatography (HPLC). Results showed that M. aeruginosa growth was significantly inhibited after 8 days of exposure, with inhibitory rate varying from 96.98% to 99.01%. The macrophyte extracts caused cyanobacterial cell membrane and antioxidant defence system damage. Thirteen different compounds were identified as allelochemical compounds that could be responsible for M. aeruginosa growth inhibition and oxidative stress. Our findings suggest that allelopathic compounds from macrophytes may be used to effectively control cyanobacteria blooms and promote the restoration of aquatic ecosystems.

Effect of Borrelia burgdorferi Outer Membrane Vesicles on Host Oxidative Stress Response.

Outer membrane vesicles (OMVs) are spherical bodies containing proteins and nucleic acids that are released by Gram-negative bacteria, including Borrelia burgdorferi, the causative agent of Lyme disease. The functional relationship between B. burgdorferi OMVs and host neuron homeostasis is not well understood. The objective of this study was to examine how B. burgdorferi OMVs impact the host cell environment. First, an in vitro model was established by co-culturing human BE2C neuroblastoma cells with B. burgdorferi B31. B. burgdorferi was able to invade BE2C cells within 24 h. Despite internalization, BE2C cell viability and levels of apoptosis remained unchanged, but resulted in dramatically increased production of MCP-1 and MCP-2 cytokines. Elevated secretion of MCP-1 has previously been associated with changes in oxidative stress. BE2C cell mitochondrial superoxides were reduced as early as 30 min after exposure to B. burgdorferi and OMVs. To rule out whether BE2C cell antioxidant response is the cause of decline in superoxides, superoxide dismutase 2 (SOD2) gene expression was assessed. SOD2 expression was reduced upon exposure to B. burgdorferi, suggesting that B. burgdorferi might be responsible for superoxide reduction. These results suggest that B. burgdorferi modulates cell antioxidant defense and immune system reaction in response to the bacterial infection. In summary, these results show that B. burgdorferi OMVs serve to directly counter superoxide production in BE2C neurons, thereby ‘priming’ the host environment to support B. burgdorferi colonization.

Screening of the Hepatotoxic Components in Fructus Gardeniae and Their Effects on Rat Liver BRL-3A Cells.

Fructus Gardeniae (FG) is a common Chinese medicine and food. However, the toxicity of FG has drawn increasing concern, especially its hepatotoxicity. The purpose of this study was to screen the hepatotoxic components of FG and evaluate their effects on rat liver BRL-3A cells. The chemical composition of FG was determined by HPLC-ESI-MS. CCK-8 assay was used to evaluate the cytotoxicity of ten chemical components from FG, and then the toxic components with significant inhibitory activity were selected for further study. The results showed that geniposide, genipin, genipin-1-gentiobioside, gardenoside, and shanzhiside all suppress cells viability. Apoptosis assays further indicated that geniposide and its metabolite genipin are the main hepatotoxic components of FG. Pretreatment of cells with geniposide or genipin increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). The activities of superoxide dismutase (SOD) and glutathione (GSH) were decreased, while the malondialdehyde (MDA) level was increased. The cell contents of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) were also increased. Molecular docking simulations were used to investigate the mechanism of FG-induced hepatotoxicity, revealing that geniposide and genipin bind strongly to the pro-inflammatory factor TNFR1 receptor of the NF-κB and MAPK signaling pathways. The obtained results strongly indicate that the hepatotoxicity of FG is caused by iridoids compounds. Genipin had the most significant hepatotoxic effect. These toxic substances destroy the cell antioxidant defense system, increasing inflammatory injury to the liver cells and leading to apoptosis and even necrosis. Thus, this study lays a foundation for toxicology research into FG and its rational application.

Lethal and sublethal effects of acetamiprid on Eisenia andrei: Behavior, reproduction, cytotoxicity and oxidative stress

The neonicotinoid acetamiprid has been suggested as a worldwide substitute for organophosphates, due to its lower toxicity. The present study assessed several acetamiprid effects on Eisenia andrei earthworms in acute contact (ranging from 1.6 × 10−5 to 0.16 μg cm−2 acetamiprid), behavioral (0.1, 0.5, 1 mg kg−1) and chronic (0.001, 0.01, 0.05 and 0.1 mg kg−1 acetamiprid) assays carried out in natural soil. Reproduction, cytotoxicity (coelomocyte density and viability), immune cell typing (eleocytes and amoebocytes) and antioxidant defense system (glutathione (GSH), catalase (CAT) and glutathione S-transferase (GST)) responses were determined. The LC50 in the acute contact test was calculated as 1.86 × 10−2 μg cm−2. Acetamiprid concentrations of 0.5 and 1 mg kg−1 led to earthworm avoidance responses (NR = 61.09 ± 10.01%) and habitat loss (NR = 78.02 ± 12.03%), respectively. Reproduction was also affected, with a decreased number of cocoons and hatchlings per cocoon observed at 0.05 and 0.1 mg kg−1. Amoebocytes were the predominant immune system cells during the 15th and 30th assay days, while eleocytes were the main cells observed at the 45th day. CAT activities on the 30th and 45th day of exposure were increased at the lowest acetamiprid concentrations (0.001 and 0.01 mg kg−1) and decreased with increasing pesticide concentration (0.05 and 0.1 mg kg−1). Maximum GST activities and GSH levels were noted at 0.01 mg kg−1 acetamiprid. However, increasing concentrations led to GST inhibition, while GSH levels were maintained. A long-term acetamiprid exposure affected earthworm reproduction, behavior and immune and antioxidant systems, which could affect the ecological soil balance and, consequently, the entire food chain.

Cytoprotective Effect of Ligustrum robustum Polyphenol Extract against Hydrogen Peroxide-Induced Oxidative Stress via Nrf2 Signaling Pathway in Caco-2 Cells.

Ligustrum robustum is a traditional herbal tea that is widely distributed in southwest China. The health effects of L. robustum are characteristics of clearing heat, antioxidant, inducing resurgence, and improving digestion. However, the molecular mechanisms related to these effects, particularly the antioxidant mechanism, have been seldom reported. The objective of this study was to assess antioxidative capacity of L. robustum, and its protective effects and mechanisms against hydrogen peroxide (H2O2) - induced toxicity in Caco-2 cells. Total phenolic contents, free radical scavenging activity, and reducing capacity of L. robustum were measured. The effects of L. robustum on the cell viability and antioxidant defense system were explored. The expression of nuclear factor E2 related factor 2 (Nrf2) and antioxidant genes: quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and glutamate cysteine ligase (GCL) were analyzed by western blot and qPCR. Pretreatment of L. robustum could significantly reduce H2O2-induced toxicity, decrease the level of reactive oxygen species (ROS) and malondialdehyde (MDA), and increase the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione reductase (GR). By activating the expression of Nrf2 and antioxidant genes (NQO1, HO-1, and GCL), L. robustum exerts cytoprotective effect in Caco-2 cells dealt with H2O2. Therefore, the well-established model of Caco-2 cells demonstrates that L. robustum may modulate the cytoprotective effect against the H2O2-induced oxidative stress through the Nrf2 signaling pathway.

The role of catalases in the prevention/promotion of oxidative stress

Catalases, heme enzymes which catalyze decomposition of hydrogen peroxide to water and molecular oxygen, are important members of the antioxidant defense system of cells of almost all aerobic organisms. However, recent studies suggest that catalase may be involved in various other processes in the cell. The paper provides a review of reactions of catalases with their main substrate, hydrogen peroxide, and with oxidizing species such as hydroxyl radical, superoxide, nitric oxide, peroxynitrite, hypochlorous acid, and singlet oxygen. A number of these individuals are formed under oxidative eustress (good stress) as well as distress (bad stress), while others only under conditions of oxidative distress. Potential biological significance of the reactions of mammalian as well as bacterial catalases with oxidizing species is discussed. The majority of these reactions inhibit catalase. Authors emphasize that catalase inhibition, which may lead to significant increase of the local concentration of hydrogen peroxide, may be detrimental to the neighboring tissues, but in some pathological states (e.g. the defense directed against pathogenic bacteria rich in catalase, or induction of apoptosis of cancer cells which possess membrane-associated catalase) it may be beneficial for the host organism.

106 - Investigating the role of catalase mimetic cerium oxide-based nanozyme to impart protection to hepatic cells from acatalasia

Cellular catalase enzyme imparts protection to cells from the deleterious effects of reactive oxygen species (ROS) produced mainly due to the decomposition of hydrogen peroxide into water and molecular oxygen. Lowered level of cellular catalase enzyme can induce several human diseases such as acatalasemia, type 2 diabetes mellitus, and vitiligo. Recent development of nanomaterials exhibiting biological enzyme like activities (nanozymes) have shown tremendous potential as biomedicines. Among them, cerium oxide nanoparticles (CeNPs) have emerged as an effective therapeutic nanozyme due to their redox-based ability to interchange the +IV or +III oxidation states from the surface “Ce” atoms. CeNPs containing high Ce +IV oxidation state in their surface “Ce” atoms are shown to exhibit hydrogen peroxide degradation activity, similar to catalase enzyme. In this study, we have investigated the ability of CeNPs to protect normal human liver cells (WRL-68) exposed with 3-Amino-1,2,4-Triazole (3-AT), which is an irreversible inhibitor of catalase enzyme. Our results revealed that CeNPs protect cells from the cytotoxic as well as genotoxic effects aroused due to the nonfunctional cellular catalase enzyme. Uptake results suggest that CeNPs are actively internalized in WRL-68 cells and scavenge the free radicals generated due to elevated levels of hydrogen peroxide inside the cells. Additionally, we also observed that CeNPs can protect hepatic cells from undergone early apoptosis than late apoptosis. Interestingly, CeNPs did not alter the natural antioxidant defense system of cells even in the absence of functional catalase enzyme, which suggest that the observed protection was probably due to the hydrogen peroxide degradation by CeNPs. The results of this study substantiate the reinforcement of CeNPs as pharmacological agents for the treatment of human diseases related to nonfunctional biological enzymes.

Bioinspired Antioxidant Defense System Constructed by Antioxidants-Eluting Electrospun F127-Based Fibers.

Cells were continuously exposed to oxidative damage by overproduction of reactive oxygen species (ROS) when they contacted implanted biomaterials. The strategy to prevent cells from oxidative injures remains a challenge. Inspired by the antioxidant defense system of cells, we constructed a biocompatible and ROS-responsive architecture on the substrate of styrene-b-(ethylene-co-butylene)-b-styrene elastomer (SEBS). The strategy was based on fabrication of architectures through reactive electrospinning of mixture including SEBS, acylated Pluronic F127, copolymer of poly(ethylene glycol) diacrylate and 1,2-ethanedithiol (PEGDA-EDT), and antioxidants (AA-2G) and ROS-triggered release of AA-2G from microfibers to detoxify the excess ROS. We demonstrated that the stable and hydrophilic architecture was constructed by phase separation of SEBS/F127 components and cross-linking between polymer chains during electrospinning; the ROS-responsive fibers controlled the release of AA-2G and the interaction of AA-2G with ROS reduced the oxidative damage to cells. The bioinspired architecture not only reduced mechanical and oxidative damage to cells but also maintained normal ROS level for physiological hemostasis. This work provides basic principles to design and develop antioxidative biomaterials for implantation in vivo.

Phosphine inhibits transcription of the catalase gene through the DRE/DREF system in Drosophila melanogaster

Phosphine (PH3) is a toxin commonly used for pest control. Its toxicity is attributed primarily to its ability to induce oxidative damage. Our previous work showed that phosphine could disrupt the cell antioxidant defence system by inhibiting expression of the catalase gene in Drosophila melanogaster (DmCAT). However, the exact mechanism of this inhibition remains unclear. Here, we implemented a luciferase reporter assay driven by the DmCAT promoter in D. melanogaster S2 cells and showed that this reporter could be inhibited by phosphine treatment. A minimal fragment of the promoter (−94 to 0 bp), which contained a DNA replication-related element (DRE) consensus motif (−78 to −85 bp), was sufficient for phosphine-mediated reporter inhibition, suggesting the involvement of the transcription factor DREF. Furthermore, phosphine treatment led to a reduction in DREF expression and consequent repression of DmCAT transcription. Our results provide new insights on the molecular mechanism of phosphine-mediated catalase inhibition. Phosphine treatment leads to reduced levels of the transcription factor DREF, a positive regulator of the DmCAT gene, thereby resulting in the repression of DmCAT at transcriptional level.

Naturally Occurring Compounds: New Potential Weapons against Oxidative Stress in Chronic Kidney Disease.

Oxidative stress is a well-described imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense system of cells and tissues. The overproduction of free radicals damages all components of the cell (proteins, lipids, nucleic acids) and modifies their physiological functions. As widely described, this condition is a biochemical hallmark of chronic kidney disease (CKD) and may dramatically influence the progression of renal impairment and the onset/development of major systemic comorbidities including cardiovascular diseases. This state is exacerbated by exposure of the body to uremic toxins and dialysis, a treatment that, although necessary to ensure patients’ survival, exposes cells to non-physiological contact with extracorporeal circuits and membranes with consequent mitochondrial and anti-redox cellular system alterations. Therefore, it is undeniable that counteracting oxidative stress machinery is a major pharmacological target in medicine/nephrology. As a consequence, in recent years several new naturally occurring compounds, administered alone or integrated with classical therapies and an appropriate lifestyle, have been proposed as therapeutic tools for CKD patients. In this paper, we reviewed the recent literature regarding the “pioneering” in vivo testing of these agents and their inclusion in small clinical trials performed in patients affected by CKD.