Imbalance In Redox Homeostasis Research Articles

Impact of Oxidative Stress on Embryogenesis and Fetal Development.

Multiple cellular processes are regulated by oxygen radicals or reactive oxygen species (ROS) where they play crucial roles as primary or secondary messengers, particularly during cell proliferation, differentiation, and apoptosis. Embryogenesis and organogenesis encompass all these processes; therefore, their role during these crucial life events cannot be ignored, more so when there is an imbalance in redox homeostasis. Perturbed redox homeostasis is responsible for damaging the biomolecules such as lipids, proteins, and nucleic acids resulting in leaky membrane, altered protein, enzyme function, and DNA damage which have adverse impact on the embryo and fetal development. In this article, we attempt to summarize the available data in literature for an in-depth understanding of redox regulation during development that may help in optimizing the pregnancy outcome both under natural and assisted conditions.

Redox Monitoring in Nuclear Medical Imaging.

Significance: The imbalance in redox homeostasis is known as oxidative stress, which is relevant to many diseases such as cancer, arteriosclerosis, and neurodegenerative disorders. Overproduction of reactive oxygen species (ROS) is one of the factors that trigger the redox state imbalance in vivo. The ROS have high reactivity and impair biomolecules, whereas antioxidants and antioxidant enzymes, such as ascorbate and glutathione, reduce the overproduction of ROS to rectify the redox imbalance. Owing to this, redox monitoring tools have been developed to understand the redox fluctuations in oxidative stress-related diseases. Recent Advances: In an attempt to monitor redox substances, including ROS and radical species, versatile modalities have been developed, such as electron spin resonance, chemiluminescence, and fluorescence. In particular, many fluorescent probes have been developed that are selective for ROS. This has significantly contributed to understanding the relevance of ROS in disease onset and progression. Critical Issues: To date, the dynamics of ROS and radical fluctuation in in vivo redox states remain unclear, and there are a few methods for the in vivo detection of redox fluctuations. Future Directions: In this review, we summarize the development of radiolabeled probes for monitoring redox-relevant species by nuclear medical imaging that is applicable in vivo. In the future, translational research is likely to be advanced through the development of highly sensitive and in vivo applicable detection methods, such as nuclear medical imaging, to clarify the underlying dynamics of ROS, radicals, and redox substances in many diseases. Antioxid. Redox Signal. 36, 797-810.

Peroxiredoxin 6 protects irradiated cells from oxidative stress and shapes their senescence-associated cytokine landscape

Cellular senescence is a complex stress response defined as an essentially irreversible cell cycle arrest mediated by the inhibition of cell cycle-specific cyclin dependent kinases. The imbalance in redox homeostasis and oxidative stress have been repeatedly observed as one of the hallmarks of the senescent phenotype. However, a large-scale study investigating protein oxidation and redox signaling in senescent cells in vitro has been lacking. Here we applied a proteome-wide analysis using SILAC-iodoTMT workflow to quantitatively estimate the level of protein sulfhydryl oxidation and proteome level changes in ionizing radiation-induced senescence (IRIS) in hTERT-RPE-1 cells. We observed that senescent cells mobilized the antioxidant system to buffer the increased oxidation stress. Among the antioxidant proteins with increased relative abundance in IRIS, a unique 1-Cys peroxiredoxin family member, peroxiredoxin 6 (PRDX6), was identified as an important contributor to protection against oxidative stress. PRDX6 silencing increased ROS production in senescent cells, decreased their resistance to oxidative stress-induced cell death, and impaired their viability. Subsequent SILAC-iodoTMT and secretome analysis after PRDX6 silencing showed the downregulation of PRDX6 in IRIS affected protein secretory pathways, decreased expression of extracellular matrix proteins, and led to unexpected attenuation of senescence-associated secretory phenotype (SASP). The latter was exemplified by decreased secretion of pro-inflammatory cytokine IL-6 which was also confirmed after treatment with an inhibitor of PRDX6 iPLA2 activity, MJ33. In conclusion, by combining different methodological approaches we discovered a novel role of PRDX6 in senescent cell viability and SASP development. Our results suggest PRDX6 could have a potential as a drug target for senolytic or senomodulatory therapy.

MiR-125b attenuates retinal pigment epithelium oxidative damage via targeting Nrf2/HIF-1α signal pathway

The retinal pigment epithelium cells (RPE) are sensitive to oxidative stimuli due to long-term exposure to various environmental stimuli. Thus, the oxidative injury of RPE cells caused by the imbalance of redox homeostasis is one of the main pathogenic factors of age-related macular degeneration (AMD). But the sophisticated mechanisms linking AMD to oxidative stress are not fully elucidated. Activation of Nrf2 signal pathway can protect RPE cells from oxidative damage. The present study investigated the regulating mechanism of miR-125b in Nrf2 cascade and evaluated its antioxidant capacity. The in vitro studies indicated that overexpression of miR-125b substantially inhibited Keap1 expression, enhanced Nrf2 expression and induced Nrf2 nuclear translocation. Importantly, functional studies demonstrated that forced expression of miR-125b could significantly elevate cell proliferation and superoxide dismutase (SOD) levels while reduce reactive oxygen species (ROS) overproduction and malondialdehyde (MDA) formation. Further studies showed that miR-125b had no effect when Nrf2 was silenced in ARPE-19 cells. Additionally, the results identified that Nrf2 silence induced ROS accumulation enhances HIF-1α protein expression, while miR-125b could offset this effect via promoting HIF-1α protein degradation. Subsequent in vivo studies demonstrated that sodium iodate induced outer retina thinner was reversed with exogenous supplementation of miR-125b, which was cancelled in Nrf2 knockout mice. In conclusion, this study illustrated that miR-125b can protect RPE from oxidative damage via targeting Nrf2/HIF-1α signal pathway and potentially may serve as a therapeutic agent of AMD.

Mixed Exposure of Persistent Organic Pollutants Alters Oxidative Stress Markers and Mitochondrial Function in the Tail of Zebrafish Depending on Sex.

Persistent organic pollutants (POPs) are lipid-soluble toxins that are not easily degraded; therefore, they accumulate in the environment and the human body. Several studies have indicated a correlation between POPs and metabolic diseases; however, their effects on mitochondria as a central organelle in cellular metabolism and the usage of mitochondria as functional markers for metabolic disease are barely understood. In this study, a zebrafish model system was exposed to two subclasses of POPs, organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), under two different conditions (solitary OCPs or OCPs with PCBs (Aroclor 1254)), and changes in the oxidative stress marker levels and mitochondrial enzyme activities in the electron transport chain of the tail were measured to observe the correlation between POPs and representative biomarkers for metabolic disease. The results indicated different responses upon exposure to OCPs and OCPs with Aroclor 1254, and accelerated toxicity was observed following exposure to mixed POPs (OCPs with Aroclor 1254). Males were more sensitive to changes in the levels of oxidative stress markers induced by POP exposure, whereas females were more susceptible to the toxic effects of POPs on the levels of mitochondrial activity markers. These results demonstrate that the study reflects real environmental conditions, with low-dose and multiple-toxin exposure for a long period, and that POPs alter major mitochondrial enzymes’ functions with an imbalance of redox homeostasis in a sex-dependent manner.

Research progress of ferroptosis and urinary tumors

Since the researchers discovered ferroptosis in 2012, they have conducted in-depth research and exploration on the mechanism of ferroptosis and its role in tumor evolution. ferroptosis is a new type of death that is different from apoptosis and necrosis. It is mainly dependent on the cell death caused by the increase of iron and lipid oxygen in the cell and the imbalance of redox homeostasis. After the development of urinary tumors in the middle and late stage, most patients have poor surgical results. Chemotherapy is usually given after surgery. However, some tumor cells are currently resistant to chemotherapy drugs. Therefore, the occurrence of ferroptosis increases a new idea in the treatment of urinary tumors. The purpose of this review is to outline the knowledge of ferroptosis mechanisms and regulation, its role in the growth and proliferation of urinary tumor cells, and to provide new strategies for the treatment of urological tumor diseases.

Direct Quantification and Visualization of Homocysteine, Cysteine, and Glutathione in Alzheimer's and Parkinson's Disease Model Tissues.

Alzheimer's disease (AD) and Parkinson's disease (PD) are chronic neurodegenerative diseases with high morbidity and mortality. Homocysteine (Hcy), cysteine (Cys), and glutathione (GSH) are closely related to AD and PD. However, the dynamics of Hcy, Cys, and GSH in the brain tissues and the potential pathogenesis between Cys/Hcy/GSH with AD and PD remain unclear. Herein, a novel fluorescent probe 1 with multiple binding sites was rationally designed and exploited for the direct quantification of serum total Hcy and Cys along with superior optical properties. Importantly, differentiation and simultaneity fluorescence imaging of Cys, Hcy, and GSH dynamics were achieved in living cells, tissues, and mouse models of AD and PD with this probe, providing direct evidences for the relationship between Hcy/Cys/GSH and AD/PD for the first time. In addition, pathogenesis studies demonstrated that elevated Hcy and Cys levels are closely related to imbalanced redox homeostasis, increased amyloid aggregates, and nerve cell cytotoxicity. These findings will greatly promote the understanding of the functions of Hcy/Cys/GSH in Alzheimer's and Parkinson's diseases, demonstrating clinical promise for the early diagnosis and prevention of AD and PD.

NADPH Oxidase (NOX) Targeting in Diabetes: A Special Emphasis on Pancreatic β-Cell Dysfunction.

In type 2 diabetes, metabolic stress has a negative impact on pancreatic β-cell function and survival (T2D). Although the pathogenesis of metabolic stress is complex, an imbalance in redox homeostasis causes abnormal tissue damage and β-cell death due to low endogenous antioxidant expression levels in β-cells. Under diabetogenic conditions, the susceptibility of β-cells to oxidative damage by NADPH oxidase has been related to contributing to β-cell dysfunction. Here, we consider recent insights into how the redox response becomes deregulated under diabetic conditions by NADPH oxidase, as well as the therapeutic benefits of NOX inhibitors, which may provide clues for understanding the pathomechanisms and developing strategies aimed at the treatment or prevention of metabolic stress associated with β-cell failure.

Therapeutic potential of N-acetyl cysteine (NAC) in preventing cytokine storm in COVID-19: review of current evidence.

Since November 2019, SARS Coronavirus 2 disease (COVID-19) pandemic has spread through more than 195 nations worldwide. Though the coronavirus infection affects all age and sex groups, the mortality is skewed towards the elderly population and the cause of death is mostly acute respiratory distress syndrome (ARDS). There are data suggesting the role of excessive immune activation and cytokine storm as the cause of lung injury in COVID-19. The excessive immune activation and cytokine storm usually occurs due to an imbalance in redox homeostasis of the individuals. Considering the antioxidant and free radical scavenging action of N acetyl cysteine (NAC), its use might be useful in COVID-19 patients by decreasing the cytokine storm consequently decreasing the disease severity. Therefore, we reviewed all the available resources pertaining to the role of reactive oxygen species (ROS) in cytokine storm and the mechanism of action of NAC in preventing ROS. We also reviewed the use of NAC in COVID-19.

Education on reactive oxygen species to lay the foundation for understanding therapeutic advances in anticancer therapy.

478 Background: The disruption of redox balance is increasingly thought to be one of the most important underlying factors contributing to the development, progression, and metastasis of cancers in human cells. This imbalance in redox homeostasis has been shown to be induced by the generation of free radicals, predominantly reactive oxygen species (ROS). Emerging data have established ROS as a new potential therapeutic target. Understanding the mechanisms associated with tumorigenesis is important to integrate novel potential therapeutic targets and understand which tumors or patient populations may benefit from ongoing research. Shortcomings in oncologists’ knowledge and confidence can hamper the integration of new treatments into the care of patients with cancer. Methods: An online continuing education (CME) activity consisted of a multi-media 30-minute video panel of two panelists discussing the mechanism, pathophysiology, and the premises for novel anti-cancer therapies. Educational effect was assessed using a repeated paired pre-/post-assessment study design. A McNemar’s test was used to identify differences between pre- and post-assessment responses. Effect size was calculated using Cohen’s d test by determining the strength of the association between the activity and the outcomes (d < .20 is modest and d ≥ .80 is large). P values were calculated and those < .05 were considered statistically significant. The activity launched 5/14/2020 and data are represented through 8/6/2020. Results: A total of 1,033 learners, of which there are 656 physicians, participated in the activity. Participating in education resulted in statistically significant improvements and noticeable educational effect and data for oncologists that answered all pre- and post-assessment questions are represented below (n = 45, p < .001, Cohen’s d = .454). Percentages represent relative rates of improvement The role of ROS on cancer cell proliferation, cancer cell toxicity, and the tumor microenvironment (67%, p < .05) The interplay of antioxidants to aid in the development of therapies to induce DNA-damaged cell death (100%; p < .001) The potential biomarkers to aid in the development of therapies to induce DNA-damaged cell death (34%; p < .05). Conclusions: This online, interactive, expert-led, CME-certified educational activity resulted in significant gains in oncologist knowledge and confidence regarding the ROS pathway and associated clinical pipeline developments Upon completion of the initiative, only 11% of oncologists were able to answer all 3 matched pre/post questions correctly, signifying the need for further education The novelty of the information to many learners demonstrate the need to continue highlighting clinical advances and molecular pathways that may have potential implications in cancer therapy progress.

Ultrasound (US)-activated redox dyshomeostasis therapy reinforced by immunogenic cell death (ICD) through a mitochondrial targeting liposomal nanosystem.

Introduction: An imbalance in redox homeostasis consistently inhibits tumor cell proliferation and further causes tumor regression. Thus, synchronous glutaminolysis inhibition and intracellular reactive oxygen (ROS) accumulation cause severe redox dyshomeostasis, which may potentially become a new therapeutic strategy to effectively combat cancer.Methods: Mitochondrial-targeting liposomal nanoparticles (abbreviated MLipRIR NPs) are synthesized by the encapsulation of R162 (inhibitor of glutamate dehydrogenase 1 [GDH1]) and IR780 (a hydrophobic sonosensitizer) within the lipid bilayer, which are exploited for ultrasound (US)-activated tumor dyshomeostasis therapy reinforced by immunogenic cell death (ICD).Results: R162 released from MLipRIR NPs disrupts the glutaminolysis pathway in mitochondria, resulting in downregulated enzymatic activity of glutathione peroxidase (GPx). In addition, loaded IR780 can generate high levels of ROS under US irradiation, which not only interrupts mitochondrial respiration to induce apoptosis but also consumes local glutathione (GSH). GSH depletion accompanied by GPx deactivation causes severe ferroptosis of tumor cells through the accumulation of lipid peroxides. Such intracellular redox dyshomeostasis effectively triggers immunogenic cell death (ICD), which can activate antitumor immunity for the suppression of both primary and distant tumors with the aid of immune checkpoint blockade.Conclusions: Taking advantage of multimodal imaging for therapy guidance, this nanoplatform may potentiate systemic tumor eradication with high certainty. Taken together, this state-of-the-art paradigm may provide useful insights for cancer management by disrupting redox homeostasis.

Ursolic acid ameliorates hypobaric hypoxia-induced skeletal muscle protein loss via upregulating Akt pathway: An experimental study using rat model.

Hypobaric hypoxic stress leads to oxidative stress, inflammation, and disturbance in protein turnover rate. Aggregately, this imbalance in redox homeostasis is responsible for skeletal muscle protein loss and a decline in physical performance. Hence, an urgent medical need is required to ameliorate skeletal muscle protein loss. The present study investigated the efficacy of ursolic acid (UA), a pentacyclic triterpene acid to ameliorate hypobaric hypoxia (HH)-induced muscle protein loss. UA is a naturally occurring pentacyclic triterpene acid present in several edible herbs and fruits such as apples. It contains skeletal muscle hypertrophy activity; still its potential against HH-induced muscle protein loss is unexplored. To address this issue, an in vivo study was planned to examine the beneficial effect of UA supplementation on HH-induced skeletal muscle loss. Male Sprague Dawley rats were exposed to HH with and without UA supplementation (20 mg/kg; oral) for 3 continuous days. The results described the beneficial role of UA as supplementation of UA with HH exposure attenuated reactive oxygen species production and oxidative protein damage, which indicate the potent antioxidant activity. Furthermore, UA supplementation enhanced Akt, pAkt, and p70S6kinase activity (Akt pathway) and lowered the pro-inflammatory cytokines in HH exposed rats. UA has potent antioxidant and anti-inflammatory activity, and it enhanced the protein content via upregulation of Akt pathway-related proteins against HH exposure. These three biological activities of UA make it a novel candidate for amelioration of HH-induced skeletal muscle damage and protein loss.

Oxidative and antioxidative stress markers in keratoconus: a systematic review and meta-analysis.

To conduct a systematic review and meta-analysis on the levels of oxidative stress markers and antioxidants in keratoconus compared to healthy subject. The PubMed, Cochrane Library, Embase, Science Direct and Google Scholar databases were searched on 1st June 2020 for studies reporting oxidative and antioxidative stress markers in keratoconus and healthy controls. Main meta-analysis was stratified by type of biomarkers, type of samples (tears, cornea, aqueous humour and blood) and type of corneal samples (stromal cells, epithelium and endothelium). We included 36 articles, for a total of 1328 keratoconus patients and 1208 healthy controls. There is an overall increase in oxidative stress markers in keratoconus compared with healthy controls (standard mean deviation (SMD)=0.94, 95% confidence interval (95% CI) 0.55-1.33), with a significant increase in reactive oxygen and nitrogen species (1.09, 0.41-1.78) and malondialdehyde (1.78, 0.83-2.73). There is an overall decrease in antioxidants in keratoconus compared with healthy controls (-0.63, -0.89 to -0.36), with a significant decrease in total antioxidant capacity/status (-1.65, -2.88 to -0.43), aldehyde/NADPH dehydrogenase (-0.77, -1.38 to -0.17), lactoferrin/transferrin/albumin (-1.92, -2.96 to -0.89) and selenium/zinc (-1.42, -2.23 to -0.61). Oxidative stress markers were higher in tears and in cornea of keratoconus than in aqueous humour, and antioxidants were decreased in tears, aqueous humour and blood without difference between sample type. Oxidative stress markers increased in stromal cells and antioxidants decreased in endothelium. Oxidative stress markers and antioxidants were dysregulated in keratoconus, involving an imbalance of redox homeostasis in tears, cornea, aqueous humour and blood.

Quercetin ameliorates reactive oxygen species generation, inflammation, mucus depletion, goblet disintegration, and tumor multiplicity in colon cancer: Probable role of adenomatous polyposis coli, β-catenin.

1,2 Dimethyl hydrazine (DMH), a cogent environmental toxicant, targets the colon. Previous reports suggest that DMH-mediated dysregulation of the Wnt/β-catenin pathway plays a vital role in the initial events of colon carcinogenesis. Our study was designed to investigate the effect of quercetin on DMH-mediated colon cancer by targeting adenomatous polyposis coli (APC) and β-catenin in Wistar rats. Animals were pretreated orally with quercetin at doses of either 25 or 50 mg/kg bodyweight (bw) and DMH at a dose of 20 mg/kg bw subcutaneously up to the 15th week and sacrificed after the 30th week. DMH administration leads to reactive oxygen species generation, resulting in an imbalance in redox homeostasis and causing membrane lipid peroxidation, which is also partly due to the decrease in the level of tissue antioxidant machinery. Increased inflammatory and proliferative proteins were observed in DMH-induced colon cancerous rats. DMH treatment also led to dysregulation in the apoptotic pathway with decreased Bax:Bcl-2 ratio. Quercetin pretreatment ameliorates DMH-induced proliferation, activities of detoxifying enzymes, and putative early markers (mucin depletion and goblet cell disintegration) in colonic tissue. It also significantly regulates APC and β-catenin expression and inhibits tumor incidence and multiplicity. Histological results further confirm the beneficial role of quercetin in averting DMH-induced pathological alterations.

NRF2 in Cardiovascular Diseases: a Ray of Hope!

Heart failure is a worldwide pandemic influencing 26 million individuals worldwide and is expanding. Imbalanced redox homeostasis in cardiac cells alters the structure and function of the cells, which leads to contractile dysfunction, myocardial hypertrophy, and fibrosis in chronic heart failure. Various targets and agents acting on these such as siRNA, miRNA, interleukin-1, opioids, vasodilators, and SGLT2 inhibitors are being evaluated for heart failure, and nuclear factor erythroid 2-related factor 2 (NRF2) is one of them. NRF2 is a master transcription factor which is expressed in most of the tissues and exhibits a major role in amplification of the antioxidant pathways associated with the enzymes present in myocardium. Increased ROS generation and PI3K-Akt signaling can activate the receptor NRF2. Various in vitro and in vivo and few clinical studies suggested NRF2 may possess a potential for targeting oxidative stress-induced cardiovascular diseases including heart failures. All these studies collectively propose that upregulation of NRF2 will attenuate the increase in hemodynamic stress and provide beneficial role in cardiovascular diseases. The current review shall familiarize readers about the regulations and functions of NRF2. We have also discussed the current evidences suggesting beneficial role of NRF2 activators in heart failure. Graphical abstract.

Discovery of a dual inhibitor of NQO1 and GSTP1 for treating glioblastoma

BackgroundGlioblastoma (GBM) is a universally lethal tumor with frequently overexpressed or mutated epidermal growth factor receptor (EGFR). NADPH quinone oxidoreductase 1 (NQO1) and glutathione-S-transferase Pi 1 (GSTP1) are commonly upregulated in GBM. NQO1 and GSTP1 decrease the formation of reactive oxygen species (ROS), which mediates the oxidative stress and promotes GBM cell proliferation.MethodsHigh-throughput screen was used for agents selectively active against GBM cells with EGFRvIII mutations. Co-crystal structures were revealed molecular details of target recognition. Pharmacological and gene knockdown/overexpression approaches were used to investigate the oxidative stress in vitro and in vivo.ResultsWe identified a small molecular inhibitor, “MNPC,” that binds to both NQO1 and GSTP1 with high affinity and selectivity. MNPC inhibits NQO1 and GSTP1 enzymes and induces apoptosis in GBM, specifically inhibiting the growth of cell lines and primary GBM bearing the EGFRvIII mutation. Co-crystal structures between MNPC and NQO1, and molecular docking of MNPC with GSTP1 reveal that it binds the active sites and acts as a potent dual inhibitor. Inactivation of both NQO1 and GSTP1 with siRNA or MNPC results in imbalanced redox homeostasis, leading to apoptosis and mitigated cancer proliferation in vitro and in vivo.ConclusionsThus, MNPC, a dual inhibitor for both NQO1 and GSTP1, provides a novel lead compound for treating GBM via the exploitation of specific vulnerabilities created by mutant EGFR.

Downregulation of Caveolin-1 and Upregulation of Deiodinase 3, Associated with Hypoxia-Inducible Factor-1α Increase, Are Involved in the Oxidative Stress of Graves' Orbital Adipocytes.

Background: Even though the clinical features of Graves' orbitopathy (GO) are well known, its exact pathogenesis remains controversial. The imbalance of redox homeostasis in the connective tissue could play a crucial role leading to an inflammatory state and edema of soft orbital tissues, thus contributing to orbital hypoxia and increase in hypoxia-inducible factor (HIF)-1α. This oxidative stress appears to target the orbital cells such as fibroblasts and also adipocytes. This study aims to explore which pathways can lead to the aforementioned oxidative stress in GO adipose cells and therefore offers new plausible therapeutic targets. Methods: Orbital fat samples were obtained from patients with GO (Western blot [WB]: n = 8, immunohistochemistry [IHC]: n = 8) and from control patients (WB: n = 5, IHC: n = 3-5). They were processed for WB analysis and IHC of the antioxidants (catalase, superoxide dismutase 1) and for HIF-1α. The expression of caveolin-1 (Cav-1) and deiodinase 3 (DIO3), known to be regulated by HIF-1α, was also analyzed by WB and IHC, as well as the targets of Cav-1: glucose transporter type 4 (Glut-4), NADPH oxidase (NOX)-2, and endothelial nitric oxide synthase (eNOS). Triiodothyronine (T3) expression was also analyzed by IHC. Results: In GO adipocytes, the expression of catalase was reduced, whereas that of HIF-1α was strongly increased. A decreased local T3 supply was associated with DIO3 upregulation. The low expression of Cav-1 in GO adipocytes was associated not only with low expression of Glut-4 but also with an increased expression of NOX-2 and active eNOS phosphorylated on serine 1177. Conclusions: Cav-1 and DIO3, both sensitive to hypoxia and to the increase of HIF-1α, play a pivotal role in the oxidative stress in GO adipocytes. DIO3 regulates the cellular supply of T3, which is essential for the cell homeostasis. Cav-1 determines the cellular glucose supply through Glut-4 and regulates the activity of NOX-2 generating superoxide anions and that of eNOS generating nitric oxide (NO).

Impact of milk thistle (Silybum marianum) on the mycotoxin caused redox-homeostasis imbalance of ducks liver

The Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEA) frequently contaminate grain crops, especially maize, the basis of poultry's feed. Mycotoxins enter the food chain and induce pathological changes in edible tissues. Milk thistle (Silybum marianum) has been used for the treatment of liver disease in humans because of its antioxidant and hepatoprotective effects, but its utility in veterinary use is poorly examined. To investigate possible protective properties against mycotoxin caused oxidative stress in poultry, pressed form of milk thistle seed (0.5%) was tested in white, female, Hungarian ducks over a feeding period of 47 days. Ducks were separated into 3 groups. The first group was fed with normal diet. The second group was fed with normal diet contaminated with DON (4.9 mg/kg) and ZEA (0.66 mg/kg). The third group received mycotoxin contaminated feed with milk thistle supplementation. Histological examination, markers of the redox status and metal element concentration measurements were carried out. The results showed alterations in the histological examination and in the redox homeostasis markers as a short-term effect by strengthening the antioxidant system. Acute exposure of mycotoxins caused an oxidative stress, which induced an effective antioxidant defensive response of the organism indicated by the free sulfhydryl group content (from 0.72 ± 0.06 to 0.77 ± 0.11) and the reducing power (0.49 ± 0.06 to 0.52 ± 0.08) elevation. The short-term free radical injury may be compensated by the liver resulting in decreased lipid peroxidation markers (malondialdehyde concentration: from 16.86 ± 0.49 to 0.94 ± 0.15, conjugated diene concentration: from 0.21 ± 0.07 to 0.17 ± 0.03). Silymarin further strengthtened the antioxidant defense by the elevation of sulfhydryl groups concentration and reducing power property resulted in decreased total scavenger capacity. However the concentration of lipid peroxidation markers were further elevated by the used antioxidant treatment (MDA: 5.2 ± 0.35, DC: 0.26 ± 0.08). In conclusion, the mycotoxin-contamination activated effectively the antioxidant system. The milk thistle supplementation has cytoprotective effects according to the histological findings, activated the antioxidant system, however the elevation of lipid peroxidation products need further explanation.

Adaptogens in chemobrain (part IV): adaptogenic plants prevent the chemotherapeutics-induced imbalance of redox homeostasis by modulation of expression of genes encoding Nrf2-mediated signaling proteins and antioxidant, metabolizing, detoxifying enzymes in neuroglia cells

Adaptogens in chemobrain (part IV): adaptogenic plants prevent the chemotherapeutics-induced imbalance of redox homeostasis by modulation of expression of genes encoding Nrf2-mediated signaling proteins and antioxidant, metabolizing, detoxifying enzymes in neuroglia cells

Quercetin Caused Redox Homeostasis Imbalance and Activated the Kynurenine Pathway

The search for new and better antimicrobial therapy is a continuous effort. Quercetin is a polyphenol with promising antimicrobial properties. However, the understanding of its antimicrobial mechanism is limited. In this study, we investigated the biochemical mechanistic action of quercetin as an antibacterial compound. Isolates of Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, and Staphylococcus aureus were initially exposed to quercetin for antibacterial evaluation. Subsequently, S. aureus (Gram-positive) and E. coli (Gram-negative) cells were exposed to quercetin with or without ascorbic acid, and cells were harvested for selected biochemical assays. These assays included redox homeostasis (lipid peroxidation, total thiol, total antioxidant capacity), nitric oxide, and kynurenine concentration as well as DNA fragmentation. The results revealed that quercetin caused lipid peroxidation in the bacterial isolates. Lipid peroxidation may indicate ensuing oxidative stress resulting from quercetin treatment. Furthermore, tryptophan degradation to kynurenine was activated by quercetin in S. aureus but not in E. coli, suggesting that local L-tryptophan concentration might become limiting for bacterial growth. These findings, considered together, may indicate that quercetin restricts bacterial growth by promoting oxidative cellular stress, as well as by reducing the local L-tryptophan availability by activating the kynurenine pathway, thus contributing to our understanding of the molecular mechanism of the antimicrobial action of quercetin.