Oxidative Stress Conditions Research Articles

Prominent transcriptomic changes in Mycobacterium intracellulare under acidic and oxidative stress.

Mycobacterium avium complex (MAC), including Mycobacterium intracellulare is a member of slow-growing mycobacteria and contributes to a substantial proportion of nontuberculous mycobacterial lung disease in humans affecting immunocompromised and elderly populations. Adaptation of pathogens in hostile environments is crucial in establishing infection and persistence within the host. However, the sophisticated cellular and molecular mechanisms of stress response in M. intracellulare still need to be fully explored. We aimed to elucidate the transcriptional response of M. intracellulare under acidic and oxidative stress conditions. At the transcriptome level, 80 genes were shown [FC] ≥ 2.0 and p < 0.05 under oxidative stress with 10mM hydrogen peroxide. Specifically, 77 genes were upregulated, while 3 genes were downregulated. In functional analysis, oxidative stress conditions activate DNA replication, nucleotide excision repair, mismatch repair, homologous recombination, and tuberculosis pathways. Additionally, our results demonstrate that DNA replication and repair system genes, such as dnaB, dinG, urvB, uvrD2, and recA, are indispensable for resistance to oxidative stress. On the contrary, 878 genes were shown [FC] ≥ 2.0 and p < 0.05 under acidic stress with pH 4.5. Among these genes, 339 were upregulated, while 539 were downregulated. Functional analysis highlighted nitrogen and sulfur metabolism pathways as the primary responses to acidic stress. Our findings provide evidence of the critical role played by nitrogen and sulfur metabolism genes in the response to acidic stress, including narGHIJ, nirBD, narU, narK3, cysND, cysC, cysH, ferredoxin 1 and 2, and formate dehydrogenase. Our results suggest the activation of several pathways potentially critical for the survival of M. intracellulare under a hostile microenvironment within the host. This study indicates the importance of stress responses in M. intracellulare infection and identifies promising therapeutic targets.

Peripheral biomarkers as a predictor of poor prognosis in severe cases of COVID-19

We evaluated glycemia and triglyceride, hepatic, muscular, and renal damage markers, redox profile, and leptin and ghrelin hormone levels in COVID-19 patients. We also conducted statistical analysis to verify the potential of biomarkers to predict poor prognosis and the correlation between them in severe cases. We assessed glycemia and the levels of triglycerides, hepatic, muscular, and renal markers in automatized biochemical analyzer. The leptin and ghrelin hormones were assessed by the ELISA assay. Severe cases presented high glycemia and triglyceride levels. Hepatic, muscular, and renal biomarkers were altered in severe patients. Oxidative stress status was found in severe COVID-19 patients. Severe cases also had increased levels of leptin. The ROC curves indicated many biomarkers as poor prognosis predictors in severe cases. The Spearman analysis showed that biomarkers correlate between themselves. Patients with COVID-19 showed significant dysregulation in the levels of several peripheral biomarkers. We bring to light that a robust panel of peripheral biomarkers and hormones predict poor prognosis in severe cases of COVID-19 and biomarkers correlate with each other. Early monitoring of these biomarkers may lead to appropriate clinical interventions in patients infected by SARS-CoV2.

Efficient Electrochemical Microsensor for the Simultaneous Measurement of Hydrogen Peroxide and Ascorbic Acid in Living Brains.

Hydrogen peroxide (H2O2) and ascorbic acid (AA), acting as two significant indicative species, correlate with the oxidative stress status in living brains, which have historically been considered to be involved mainly in neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and Parkinson's disease (PD). The development of efficient biosensors for the simultaneous measurement of their levels in living brains is vital to understand their roles played in the brain and their interactive relationship in the progress of these diseases. Herein, a robust ratiometric electrochemical microsensor was rationally designed to realize the determination of H2O2 and AA simultaneously. Therefore, a specific probe was designed and synthesized with both recognition units responsible for reacting with H2O2 to produce a detectable signal on the microsensor and linkage units helping the probe modify onto the carbon substrate. A topping ingredient, single-walled carbon nanotubes (SWCNTs) was added on the surface of the electrode, with the purpose of not only facilitating the oxidation of AA but also absorbing methylene blue (MB), prompting to read out the inner reference signal. This proposed electrochemical microsensor exhibited a robust ability to real-time track H2O2 and AA in linear ranges of 0.5-900 and 10-1000 μM with high selectivity and accuracy, respectively. Eventually, the efficient electrochemical microsensor was successfully applied to the simultaneous measurement of H2O2 and AA in the rat brain, followed by microinjection, and in the PD mouse brain.

Screening and evaluation of prebiotic exopolysaccharide of Lactobacillus plantarum on treating IBD in mice

PurposeThis research aimed at ascertaining the effects of prebiotic exopolysaccharide on inflammatory bowel disease (IBD). MethodsWe studied the prebiotic activity of EPSs from 5 Lactobacillus plantarum strains using an in vitro gut microbiota model. The EPS with the strongest activity was fed to DSS-induced IBD mice. We then examined the mice's gut microbiota, serum cytokines, oxidative stress, and metabolic conditions. ResultsIn the in vitro experiment, Only EPS32 of the 5 EPSs exhibited a good prebiotic activity similar to inulin. The EPS32 is composed of rhamnose, fructose, and galactose in a ratio of 8.2:1:1.7. When feeding mice with 50 mg/kgBW/day EPS32 for 10 days, it significantly alleviated the IBD symptoms including restoring gut microbiota dysbiosis, increasing short-chain fatty acid production, lowering pro-inflammatory cytokine levels, lowering oxidative stress in the lumen, and restore the metabolic conditions. ConclusionContinuous intake of prebiotic EPS can effectively alleviate IBD symptoms.

Intelligent salivary biosensors for periodontitis: in vitro simulation of oral oxidative stress conditions.

One of the most common oral diseases affecting millions of people worldwide is periodontitis. Usually, proteins in body fluids are used as biomarkers of diseases. This study focused on hydrogen peroxide, lipopolysaccharide (LPS), and lactic acid as salivary non-protein biomarkers for oxidative stress conditions of periodontitis. Electrochemical analysis of artificial saliva was done using Gamry with increasing hydrogen peroxide, bLPS, and lactic acid concentrations. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were conducted. From EIS data, change in capacitance and CV plot area were calculated for each test condition. Hydrogen peroxide groups had a decrease in CV area and an increase in percentage change in capacitance, lipopolysaccharide groups had a decrease in CV area and a decrease in percentage change in capacitance, and lactic acid groups had an increase of CV area and an increase in percentage change in capacitance with increasing concentrations. These data showed a unique combination of electrochemical properties for the three biomarkers. Scanning electron microscopy (SEM) with energy dispersive spectroscopy (EDS) employed to observe the change in the electrode surface and elemental composition data present on the sensor surface also showed a unique trend of elemental weight percentages. Machine learning models using hydrogen peroxide, LPS, and lactic acid electrochemical data were applied for the prediction of risk levels of periodontitis. The detection of hydrogen peroxide, LPS, and lactic acid by electrochemical biosensors indicates the potential to use these molecules as electrochemical biomarkers and use the data for ML-driven prediction tool for the periodontitis risk levels.

Atox1 protects hippocampal neurons after traumatic brain injury via DJ-1 mediated anti-oxidative stress and mitophagy

Regulation of the oxidative stress response is crucial for the management and prognosis of traumatic brain injury (TBI). The copper chaperone Antioxidant 1 (Atox1) plays a crucial role in regulating intracellular copper ion balance and impacting the antioxidant capacity of mitochondria, as well as the oxidative stress state of cells. However, it remains unknown whether Atox1 is involved in modulating oxidative stress following TBI. Here, we investigated the regulatory role of Atox1 in oxidative stress on neurons both in vivo and in vitro, and elucidated the underlying mechanism through culturing hippocampal HT-22 cells with Atox1 mutation. The expression of Atox1 was significantly diminished following TBI, while mice with overexpressed Atox1 exhibited a more preserved hippocampal structure and reduced levels of oxidative stress post-TBI. Furthermore, the mice displayed notable impairments in learning and memory functions after TBI, which were ameliorated by the overexpression of Atox1. In the stretch injury model of HT-22 cells, overexpression of Atox1 mitigated oxidative stress by preserving the normal morphology and network connectivity of mitochondria, as well as facilitating the elimination of damaged mitochondria. Mechanistically, co-immunoprecipitation and mass spectrometry revealed the binding of Atox1 to DJ-1. Knockdown of DJ-1 in HT-22 cells significantly impaired the antioxidant capacity of Atox1. Mutations in the copper-binding motif or sequestration of free copper led to a substantial decrease in the interaction between Atox1 and DJ-1, with overexpression of DJ-1 failing to restore the antioxidant capacity of Atox1 mutants. The findings suggest that DJ-1 mediates the ability of Atox1 to withstand oxidative stress. And targeting Atox1 could be a potential therapeutic approach for addressing post-traumatic neurological dysfunction.

Study of the Fenton Oxidative Reaction on a Culture of Human Fibroblast Cells Incubated with Ablated CeO&lt;sub&gt;2&lt;/sub&gt; Particles

Purpose. Study of the bioprotective properties of ablated cerium dioxide nanoparticles in relation to immortalized human fibroblasts under conditions of oxidative stress caused by the Fenton reaction.Methods. Cerium dioxide nanoparticles with pronounced antioxidant properties were obtained using laser ablation. The average maximum sizes of ablated particles of oxidized cerium in non-centrifuged and centrifuged at a speed of 1000 rpm nanodispersed aqueous solutions were revealed using the method of atomic force microscopy. The spectrophotometric method revealed that ablated cerium dioxide nanoparticles exhibit antioxidant properties and prevent the degradation of the methylene blue dye during the Fenton reaction. Cell culture samples were mapped using scanning electron microscopy using an energy-dispersive attachment after their incubation with ablated cerium dioxide nanoparticles. Using MTT analysis, the effect of ablated cerium dioxide nanoparticles on the survival of BJ TERT cell culture in the Fenton reaction was studied. Non-centrifuged and centrifuged at a speed of 1000 rpm nanodispersed solutions of oxidized cerium were used. The antioxidant activity of cerium dioxide nanoparticles after 6- and 24-hour incubation was studied.Results. The average limiting sizes of ablated cerium dioxide nanoparticles have been established, the values of which are (61,95±0,1) nm for a non-centrifuged aqueous solution and (56,59±0,1) nm for an aqueous solution centrifuged at a microcentrifuge speed of 1000 rpm. It was revealed that in the presence of ablated cerium dioxide nanoparticles, the degree of oxidative degradation of methylene blue during the Fenton reaction was significantly reduced. It was found that with an increase in the concentration of ablated cerium dioxide nanoparticles from 20 to 1000 mg/l, their antioxidant effect increased. From the obtained SEM images of cell cultures with ablated cerium dioxide nanoparticles, it follows that the nanoparticles are captured by cells during incubation and can have a significant effect on oxidative processes during the Fenton reaction. Statistical analysis based on the results of the MTT assay showed that 6-hour and 24-hour incubation with ablated cerium dioxide nanoparticles had a pronounced protective effect on the BJ TERT cell line.Conclusion. This work shows that during the Fenton reaction, cerium dioxide nanoparticles prevent the oxidative degradation of the methylene blue dye. When immortalized human fibroblasts are incubated, ablated cerium oxide nanoparticles are taken up by the cells and have a significant protective effect on them in the oxidative reaction. The high antioxidant activity of nanoparticles is determined by the high content of functional defects on the surface of nanoparticles obtained under sharply nonequilibrium conditions of laser ablation.

Effects of Regular Exercise on the Biochemical, Oxidative, and Inflammatory Profiles and Quality of Life in Older Spaniards with Metabolic Syndrome.

Metabolic syndrome increases the risk of developing diabetes and cardiovascular disease. The regular practice of physical activity is a crucial factor for healthy aging and for controlling and preventing chronic diseases. To assess the effects of regular physical activity on the biochemical and inflammatory profiles, as well as the quality of life of older adults diagnosed with metabolic syndrome. Participants (aged 55-70 years; living in the Balearic Islands, Spain) were divided into two groups (n = 50 each) according to the degree of physical activity measured by metabolic equivalents of task (METs). Anthropometric parameters, blood pressure, biochemical and hematological parameters, and inflammatory biomarkers were measured. Beck Depression Inventory and adherence to the Mediterranean diet questionnaires, as well as the Dietary Inflammatory Index, chair test, health-related quality of life (HRQoL), and Rapid Assessment of Physical Activity, were also determined. The characterization of the patients was similar in both groups, showing a homogeneous sample. The group with the highest METs experienced a decrease in depression and an increase in the intensity of physical activity. Adherence to the Mediterranean diet and HRQoL physical dimensions increased in participants with the highest METs, also showing a decrease in glycemia and glycosylated hemoglobin values. Inflammatory biomarkers, including tumor necrosis factor alpha, interleukin-6, interleukin-1β, and osteoprotegerin, decreased in patients practicing more physical activity. High levels of physical activity are related to a healthier lifestyle, characterized by high adherence to the Mediterranean diet, decreased depressive behavior, oxidative stress, and inflammatory status in older people with metabolic syndrome.

Oxidative Stress and Antioxidant Status in Adult Patients with Transfusion-Dependent Thalassemia: Correlation with Demographic, Laboratory, and Clinical Biomarkers.

Iron overload in beta transfusion-dependent thalassemia (β-TDT) may provoke oxidative stress and reduction of the antioxidant defenses, with serious consequences for the disease course and complications. The present study evaluated the oxidant/antioxidant status of β-TDT patients and its correlation with demographic, clinical, laboratory, and instrumental biomarkers. The OXY-adsorbent assay and the d-ROMs (Diacron, Grosseto, Italy) were evaluated in 58 β-TDT patients (mean age: 37.55 ± 7.83 years, 28 females) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload was quantified with R2* magnetic resonance imaging. Mean OXY was 323.75 ± 113.19 μmol HClO/mL and 39 (67.2%) patients showed a decreased OXY-Adsorbent level (<350 μmol HClO/mL), of whom 22 (37.9%) showed severely reduced levels. Mean d-ROMs was 305.12 ± 62.19 UA; 12 (20.7%) patients showed oxidative stress, and 4 (6.9%) elevated oxidative stress. OXY showed a significant negative correlation with global and segmental cardiac iron levels. D-ROMs levels significantly correlated with markers of cardiovascular risk (aging, glycemia, and N-terminal pro-B-type natriuretic peptide). Antioxidant depletion is frequent in β-TDT patients, where OXY might serve as additive biomarker to assess heart iron status, whereas the d-ROMs might be helpful to assess the cardiovascular risk burden.

Apigenin Alleviates Autistic-like Stereotyped Repetitive Behaviors and Mitigates Brain Oxidative Stress in Mice.

Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10-30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 mg/kg, i.p.). BTBR mice pretreated with APG (20 mg/kg) or ARP (1 mg/g, i.p.) displayed significant improvements in the marble-burying test (MBT), cotton-shredding test (CST), and self-grooming test (SGT) (all p < 0.05). However, a lower dose of APG (10 mg/kg, i.p.) failed to modulate behaviors in the MBT or SGT, but significantly attenuated the increased shredding behaviors in the CST of tested mice. Moreover, APG (10-30 mg/kg, i.p.) and ARP (1 mg/kg) moderated the disturbed levels of oxidative stress by mitigating the levels of catalase (CAT) and superoxide dismutase (SOD) in the hippocampus and cerebellum of treated BTBR mice. In patch clamp studies in hippocampal slices, the potency of choline (a selective agonist of α7-nAChRs) in activating fast inward currents was significantly potentiated following incubation with APG. Moreover, APG markedly potentiated the choline-induced enhancement of spontaneous inhibitory postsynaptic currents. The observed results propose the potential therapeutic use of APG in the management of ASD. However, further preclinical investigations in additional models and different rodent species are still needed to confirm the potential relevance of the therapeutic use of APG in ASD.

The antioxidant effect of tetrahedral framework nucleic acid-based delivery of small activating RNA targeting DJ-1 on retinal oxidative stress injury.

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are the world's leading causes of blindness. The retinal pigment epithelium (RPE) and vascular endothelial cell exposed to oxidative stress is the major cause of AMD and DR. DJ-1, an important endogenous antioxidant, its overexpression is considered as a promising antioxidant treatment for AMD and DR. Here, we modified the tetrahedral frame nucleic acids (tFNAs) with DJ-1 saRNAs as a delivery system, and synthesized a novel nanocomplex (tFNAs-DJ-1 saRNAs). In vitro studies show that tFNAs-DJ-1 saRNAs can efficiently transfer DJ-1 saRNAs to human umbilical vein endothelial cells (HUVECs) and ARPE-19s, and significantly increased their cellular DJ-1 level. Reactive oxygen species expression in H2O2-treated HUVECs and ARPE-19s were decreased, cell viability was enhanced and cell apoptosis were inhibited when tFNAs-DJ-1 saRNAs were delivered. Moreover, tFNAs-DJ-1 saRNAs preserved mitochondrial structure and function under oxidative stress conditions. In the aspect of molecular mechanism, tFNAs-DJ-1 saRNAs activated Erk and Nrf2 pathway, which might contribute to its protective effects against oxidative stress damage. To conclude, this study shows the successfully establishment of a simple but effective delivery system of DJ-1 saRNAs associated with antioxidant effects in AMD and DR, which may be a promising agent for future treatment in oxidative stress-related retinal disorders.

Analytical method development, identification, and characterization of stress degradation products of idelalisib by ultrahigh-performance liquid chromatography with photodiode array and ultrahigh-performance liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometry studies.

As per International Council for Harmonization (ICH) drug stability test guideline Q1A(R2), inherent stability characteristics of a drug should be studied. This work was designed to investigate inherent degradation characteristics of the drug idelalisib under ICH prescribed stress conditions, identify its degradation products, and postulate their corresponding degradation pathways. Idelalisib was subjected to the ICH prescribed conditions of hydrolytic (neutral, acidic, and alkaline), photolytic, oxidative, and thermal stress according to ICH guideline Q1A(R2). An ultrahigh-performance liquid chromatography with photodiode array (UHPLC-PDA) method was developed to adequately resolve the drug from its degradation products, validated as per the ICH guidelines, and subsequently extended to UHPLC with electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOFMS) studies to identify the degradation products. Significant degradation was noted under conditions of acidic/alkaline hydrolysis, acid photolysis, and oxidative stress. The UHPLC/ESI-QTOFMS studies revealed the generation of four degradation products (I-IV), which were satisfactorily resolved from the drug by UHPLC on a Kinetex® C18 (100 × 4.6mm; 2.6μm) column by the developed isocratic elution method. Detection wavelength was selected as 270 nm. All the degradation products (I-IV) could be identified and characterized from their mass spectral data. The degradation pathways for the generation of various products from the drug were postulated. A UHPLC-PDA method was developed and validated for idelalisib. Four degradation products of idelalisib were revealed through UHPLC/ESI-QTOFMS studies, and corresponding degradation pathways were postulated for the same.

Fabrication of a tailor-made conductive polyaniline/ascorbic acid-coated nanofibrous mat as a conductive and antioxidant cell-free cardiac patch

Polyaniline (PANI) was in-situ polymerized on nanofibrous polycaprolactone mats as cell-free antioxidant cardiac patches (CPs), providing electrical conductivity and antioxidant properties. The fabricated CPs took advantage of intrinsic and additive antioxidant properties in the presence of PANI backbone and ascorbic acid as a biocompatible dopant of PANI. The antioxidant nature of CPs may reduce the serious repercussions of oxidative stress, produced during the ischemia-reperfusion (I/R) process following myocardial infarction. The polymerization parameters were considered as aniline (60 mM, 90 mM, and 120 mM), ascorbic acid concentrations ([aniline]:[ascorbic acid] = 3:0, 3:0.5, 3:1, 3:3), and polymerization time (1 h and 3 h). Mainly, the more aniline concentrations and polymerization time, the less sheet resistance was obtained. 1,1 diphenyl-2-picrylhydrazyl (DPPH) assay confirmed the dual antioxidant properties of prepared samples. The advantage of the employed in-situ polymerization was confirmed by the de-doping/re-doping process. Non-desirable groups were excluded based on their electrical conductivity, antioxidant properties, and biocompatibility. The remained groups protected H9c2 cells against oxidative stress and hypoxia conditions. Selected CPs reduced the intracellular reactive oxygen species content and mRNA level of caspase-3 while the Bcl-2 mRNA level was improved. Also, the selected cardiac patch could attenuate the hypertrophic impact of hydrogen peroxide on H9c2 cells. The in vivo results of the skin flap model confirmed the CP potency to attenuate the harmful impact of I/R.

Modulation of the Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by the probiotic Limosilactobacillus reuteri DSM 17938 prevents diet-induced rat brain dysfunction

Dietary patterns high in fat and sugar promote brain dysfunction, but the preventive efficacy of probiotics has been little explored. This study investigated whether the administration of Limosilactobacillus reuteri DSM 17938 (L.reuteri; 108 CFU/day) counteracts cognitive dysfunction and brain redox unbalance induced in male Wistar rats fed a western diet (WD) for 8 weeks.The results showed that L. reuteri prevented the WD-associated impairment in brain memory function, as evaluated by NOR test, and consistently increased specific molecular markers of synaptic plasticity. The condition of oxidative stress induced by WD, namely enhanced oxidation to proteins and lipids, increased oxidants-producing enzymes as well as reduced nuclear Nrf2 and Nrf2-dependent antioxidant enzymes, was ameliorated by the probiotic. Unexpectedly, mitochondria displayed a diet-induced increase in oxidative capacity, not modified by the probiotic. A protective effect of the probiotic on gut absorption of fructose and its further delivery to brain was evidenced as mechanism involved in cortex redox homeostasis. These findings evidence the potential utility of L. reuteri against WD-induced brain dysfunction and implicate the Nrf2 pathway as a potential mechanism for this effect.

Dietary fat supplementation relieves cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis in pigs.

Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy metabolism, and the mechanisms by which it regulates host energy metabolism at cold temperatures have rarely been illustrated. In this study, we evaluated the status of glycolipid metabolism and oxidative stress in pigs based on the gut-liver axis and propose that AMP-activated protein kinase (AMPK) is a key target for alleviating energy stress at cold temperatures by dietary fat supplementation. Dietary fat supplementation alleviated the negative effects of cold temperatures on growth performance and digestive enzymes, while hormonal homeostasis was also restored. Moreover, cold temperature exposure increased glucose transport in the jejunum. In contrast, we observed abnormalities in lipid metabolism, which was characterized by the accumulation of bile acids in the ileum and plasma. In addition, the results of the ileal metabolomic analysis were consistent with the energy metabolism measurements in the jejunum, and dietary fat supplementation increased the activity of the mitochondrial respiratory chain and lipid metabolism. As the central nexus of energy metabolism, the state of glycolipid metabolism and oxidative stress in the liver are inconsistent with that in the small intestine. Specifically, we found that cold temperature exposure increased glucose transport in the liver, which fully validates the idea that hormones can act on the liver to regulate glucose output. Additionally, dietary fat supplementation inhibited glucose transport and glycolysis, but increased gluconeogenesis, bile acid cycling, and lipid metabolism. Sustained activation of AMPK, which an energy receptor and regulator, leads to oxidative stress and apoptosis in the liver; dietary fat supplementation alleviates energy stress by reducing AMPK phosphorylation. Cold stress reduced the growth performance and aggravated glycolipid metabolism disorders and oxidative stress damage in pigs. Dietary fat supplementation improved growth performance and alleviated cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis. In this study, we highlight the importance of AMPK in dietary fat supplementation-mediated alleviation of host energy stress in response to environmental changes.

Investigating the impact of Psidium guajava leaf hydroalcoholic extract in improving glutamatergic toxicity-induced oxidative stress in Danio rerio larvae

ABSTRACT Glutamate is one of the predominant excitatory neurotransmitters released from the central nervous system; however, at high concentrations, this substance may induce excitotoxicity. This phenomenon is involved in numerous neuropathologies. At present, clinically available pharmacotherapeutic agents to counteract glutamatergic excitotoxicity are not completely effective; therefore, research to develop novel compounds is necessary. In this study, the main objective was to determine the pharmacotherapeutic potential of the hydroalcoholic extract of Psidium guajava (PG) in a model of oxidative stress-induced by exposure to glutamate utilizing Danio rerio larvae (zebrafish) as a model. Data showed that treatment with glutamate produced a significant increase in oxidative stress, chromatin damage, apoptosis, and locomotor dysfunction. All these effects were attenuated by pre-treatment with the classical antioxidant N-acetylcysteine (NAC). Treatment with PG inhibited oxidative stress responsible for cellular damage induced by glutamate. However, exposure to PG failed to prevent glutamate-initiated locomotor damage. Our findings suggest that under conditions of oxidative stress, PG can be considered as a promising candidate for treatment of glutamatergic excitotoxicity and consequent neurodegenerative diseases.

Ursodeoxycholic and chenodeoxycholic bile acids attenuate systemic and liver inflammation induced by lipopolysaccharide in rats.

Bacterial lipopolysaccharide (LPS) induces general inflammation, by activating pathways involving cytokine production, blood coagulation, complement system activation, and acute phase protein release. The key cellular players are leukocytes and endothelial cells, that lead to tissue injury and organ failure. The aim of this study was to explore the anti-inflammatory, antioxidant, and cytoprotective properties of two bile acids, ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in LPS-induced endotoxemia in rats. The experiment involved six distinct groups of Wistar rats, each subjected to different pretreatment conditions: control and LPS groups were pretreated with propylene glycol, as a bile acid solvent, while the other groups were pretreated with UDCA or CDCA for 10 days followed by an LPS injection on day 10. The results showed that both UDCA and CDCA reduced the production of pro-inflammatory cytokines: TNF-α, GM-CSF, IL-2, IFNγ, IL-6, and IL-1β and expression of nuclear factor-κB (NF-κB) induced by LPS. In addition, pretreatment with these bile acids showed a positive impact on lipid profiles, a decrease in ICAM levels, an increase in antioxidant activity (SOD, |CAT, GSH), and a decrease in prooxidant markers (H2O2 and O2-). Furthermore, both bile acids alleviated LPS-induced liver injury. While UDCA and CDCA pretreatment attenuated homocysteine levels in LPS-treated rats, only UDCA pretreatment showed reductions in other serum biochemical markers, including creatine kinase, lactate dehydrogenase, and high-sensitivity troponin I. It can be concluded that both, UDCA and CDCA, although exerted slightly different effects, can prevent the inflammatory responses induced by LPS, improve oxidative stress status, and attenuate LPS-induced liver injury.

Subchronic Exposure to Mixture of Cadmium, Copper, and Nickel Induces Neurobehavioral Deficits and Hippocampal Oxidative Stress of Wistar Rats.

The present study was aimed at evaluating the influence of the subchronic exposure of cadmium (Cd), copper (Cu), and nickel (Ni) mixtures on affective behaviors, memory impairment, and oxidative stress (OS) in the hippocampus. Thirty male Wistar rats were divided into 5 equal groups. Group 1 (control) received a saline solution (NaCl 0.9%). Groups 2, 3, and 4 received Cd (0.25 mg/kg), Cu (0.5 mg/kg), and Ni (0.25 mg/kg), respectively, while group 5 received a Cd, Cu, and Ni mixture through intraperitoneal injections for 2 months. After the exposure period, all rats were submitted to behavioral tests. Subsequently, OS markers and histological changes in the rats' hippocampi were assessed. Results showed that a 2-month exposure to the mixtures of metals (MM) has led to higher anxiety-like and depression-like behaviors and cognitive deficits in rats when compared to the control group and the individual metals. Furthermore, the MM induced heightened OS, evidenced by the rise in lipid peroxidation and nitric oxide levels. These effects were accompanied by a decrease in superoxide dismutase and catalase activities in the hippocampus. The histopathological analysis also supported that MM caused a neuronal loss in the CA3 sub-region. Overall, this study underscores that subchronic exposure to the Cd, Cu, and Ni mixture induces an OS status and histological changes in the hippocampus, with important affective and cognitive behavior variations in rats.

A role of methionines in the functioning of oxidatively modified fibrinogen

Posttranslational modifications in fibrinogen resulting from induced oxidation or oxidative stress in the organism can have deleterious influence on optimal functioning of fibrinogen, causing a disturbance in assembly and properties of fibrin. The protective mechanism supporting the ability of fibrinogen to function in ROS-generating environment remains completely unexplored. The effects of very low and moderately low HOCl/−OCl concentrations on fibrinogen oxidative modifications, the fibrin network structure as well as the kinetics of both fibrinogen-to-fibrin conversion and fibrin hydrolysis have been explored in the current study. As opposed to 25 Μm, HOCl/−OCl, 10 μM HOCl/−OCl did not affect the functional activity of fibrinogen. It is shown for the first time that a number of Met residues, AαMet476, AαMet517, AαMet584, BβMet367, γMet264, and γMet94, identified in 10 μM HOCl/–OCl fibrinogen by the HPLC-MS/MS method, operate as ROS scavengers, performing an important antioxidant function. In turn, this indicates that the fibrinogen structure is adapted to the detrimental action of ROS. The results obtained in our study provide evidence for a protective mechanism responsible for maintaining the structure and functioning of fibrinogen molecules in the bloodstream under conditions of mild and moderate oxidative stress.

Panax notoginseng saponins prevent dementia and oxidative stress in brains of SAMP8 mice by enhancing mitophagy

BackgroundMitochondrial dysfunction is one of the distinctive features of neurons in patients with Alzheimer’s disease (AD). Intraneuronal autophagosomes selectively phagocytose and degrade the damaged mitochondria, mitigating neuronal damage in AD. Panax notoginseng saponins (PNS) can effectively reduce oxidative stress and mitochondrial damage in the brain of animals with AD, but their exact mechanism of action is unknown.MethodsSenescence-accelerated mouse prone 8 (SAMP8) mice with age-related AD were treated with PNS for 8 weeks. The effects of PNS on learning and memory abilities, cerebral oxidative stress status, and hippocampus ultrastructure of mice were observed. Moreover, changes of the PTEN-induced putative kinase 1 (PINK1)-Parkin, which regulates ubiquitin-dependent mitophagy, and the recruit of downstream autophagy receptors were investigated.ResultsPNS attenuated cognitive dysfunction in SAMP8 mice in the Morris water maze test. PNS also enhanced glutathione peroxidase and superoxide dismutase activities, and increased glutathione levels by 25.92% and 45.55% while inhibiting 8-hydroxydeoxyguanosine by 27.74% and the malondialdehyde production by 34.02% in the brains of SAMP8 mice. Our observation revealed the promotion of mitophagy, which was accompanied by an increase in microtubule-associated protein 1 light chain 3 (LC3) mRNA and 70.00% increase of LC3-II/I protein ratio in the brain tissues of PNS-treated mice. PNS treatment increased Parkin mRNA and protein expression by 62.80% and 43.80%, while increasing the mRNA transcription and protein expression of mitophagic receptors such as optineurin, and nuclear dot protein 52.ConclusionPNS enhanced the PINK1/Parkin pathway and facilitated mitophagy in the hippocampus, thereby preventing cerebral oxidative stress in SAMP8 mice. This may be a mechanism contributing to the cognition-improvement effect of PNS.