Inducible Oxide Research Articles

Atractylenolide Ⅲ partially alleviates tunicamycin-induced damage in porcine oocytes during in vitro maturation by reducing oxidative stress.

Assisted reproductive technology (ART) is widely used to address infertility and enhance reproductive outcomes in livestock. Among various ART techniques, in vitro maturation (IVM) is commonly used to obtain high-quality oocytes but is susceptible to oxidative stress. In traditional Chinese medicine, Rhizoma Atractylodis Macrocephalae (Bai Zhu) is used to enhance maternal and fetal health. Atractylenolide Ⅲ (AⅢ), a major component of Bai Zhu, has shown both antioxidant properties and oxidative stress induction, leading to controversy. This study used porcine oocytes as a model to investigate the effects of AⅢ under tunicamycin (TM)-induced oxidative stress. During IVM, oocytes were treated with various concentrations of AⅢ and a constant dose of TM. AⅢ promoted oocyte maturation and cumulus cell expansion, with the optimal concentration being 1 mg/L. AⅢ reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, indicating reduced oxidative damage. Mitochondrial function and membrane potential (MMP) were preserved in AⅢ-treated oocytes. Additionally, AIII could alleviate TM-induced endoplasmic reticulum (ER) stress, as shown by decreased mRNA expression of ER stress markers. Following parthenogenetic activation (PA), AⅢ-treated oocytes exhibited increased cleavage and blastocyst formation rates with reduced apoptosis compared to the TM group. These findings suggest that AⅢ protects against oxidative stress, improving oocyte quality and developmental potential, with potential applications in ART.

IGF2BP3 curbed by miR-15c-3p restores disrupted lipid storage and progesterone secretion in chicken granulosa cells under oxidative stress through AKT-Raf1-ERK1/2 signaling pathway.

For commercial laying hens, the continuous high-intensity ovulation process leads to a significant accumulation of reactive oxygen species (ROS) in the granulosa cells, inducing oxidative stress, which accelerates ovarian aging and shortens the peak laying period. The molecular mechanisms underlying this process remain poorly understood. Therefore, we modeled the processes of oxidative stress and antioxidant in chicken granulosa cells. Small RNA sequencing revealed that miR-15c-3p expression was elevated by oxidative stress induction and attenuated by antioxidant curcumin. Functional validation with miR-15c-3p mimic and inhibitor confirmed the role of miR-15c-3p in exacerbating oxidative stress and resultant suppression of lipid droplet storage and progesterone secretion in chicken granulosa cells by targeting insulin-like growth factor 2 binding protein 3 (IGF2BP3). These regulatory effects were mediated through the sequential downstream signaling cascade of AKT-Raf1-ERK1/2. In conclusion, IGF2BP3 curbed by miR-15c-3p restores disrupted lipid storage and progesterone secretion in chicken granulosa cells under oxidative stress through AKT-Raf1-ERK1/2 signaling pathway. These findings offer new insights into the molecular mechanisms by which oxidative stress damages reproductive capacity and a theoretical basis for mitigating oxidative stress in laying hens through genetic improvement.

Calcium hydroxide nanoparticles induce cell death, genomic instability, oxidative stress and apoptotic gene dysregulation on human HepG2 cells

Calcium hydroxide nanoparticles (Ca(OH)2NPs) possess potent antimicrobial activities and unique physical and chemical properties, making them valuable across various fields. However, limited information exists regarding their effects on genomic DNA integrity and their potential to induce apoptosis in normal and cancerous human cell lines. This study thus aimed to evaluate the impact of Ca(OH)2NPs on cell viability, genomic DNA integrity, and oxidative stress induction in human normal skin fibroblasts (HSF) and cancerous hepatic (HepG2) cells. Cell viability and genomic DNA stability were assessed using the Sulforhodamine B (SRB) assay and alkaline comet assay, respectively. Reactive oxygen species (ROS) levels were measured using 2,7-dichlorofluorescein diacetate, while the expression level of apoptosis-related genes (p53, Bax, and Bcl-2) were quantified using real-time PCR (qRT-PCR). The SRB cytotoxicity assay revealed that a 48-hour exposure to Ca(OH)2NPs caused concentration-dependent cell death and proliferation inhibition in both HSF and HepG2 cells, with IC50 values of 271.93 µg/mL for HSF and 291.8 µg/mL for HepG2 cells. Treatment with the IC50 concentration of Ca(OH)2NPs selectively induced significant DNA damage, excessive ROS generation, and marked dysregulation of apoptotic (p53 and Bax) and anti-apoptotic (Bcl-2) gene expression in HepG2 cells, triggering apoptosis. In contrast, exposure of HSF cells to the IC50 concentration of Ca(OH)2NPs caused no significant changes in genomic DNA integrity, ROS generation, or apoptotic gene expression. These findings indicate that Ca(OH)2NPs exhibit concentration-dependent cytotoxicity in both normal HSF and cancerous HepG2 cells. However, exposure to the IC50 concentration was non-genotoxic to normal HSF cells while selectively inducing genotoxicity and apoptosis in HepG2 cancer cells through DNA breaks and ROS-mediated mechanisms. Further studies are required to explore the biological and toxicological properties and therapeutic potential of Ca(OH)2NPs in hepatic cancer treatment.

Current understanding of human bioaccumulation patterns and health effects of exposure to perfluorooctane sulfonate (PFOS).

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant of global concern due to its environmental presence,bioaccumulative potential and toxicological impacts. This review synthesizes current knowledge regarding PFOS exposure, bioaccumulation patterns and adverse health outcomes in human population. Analysis of worldwide biomonitoring data, and epidemiological studies reveals PFOS systemic effects, including immunological dysfunction (decreased vaccine response), developmental toxicity (reduced birth weight), hepatic metabolic disruption, potential carcinogenogenicity, and reproductive abnormalities. At the molecular level, PFOS induces toxicity through multiple pathways, including PI3K/AKT/mTOR pathway inhibition, PPARα activation, NF-κB signaling modulation, and oxidative stress induction. Recent advances in analytical methodologies have enhanced our understanding of PFOS distribution and fate, while evolving egulatory frameworks attempts to address its risk. This review identifies critical research gaps and emphasized the need for coordinated multidisciplinary approaches to address this persistent environmental contaminant.

Development of a method for measuring the oxidation induction period of stabilized high-pressure polyethylene

Choice of boundary conditions and optimal parameters for measuring of oxidation induction time of cable polyethylene grade 153-01K with amine and phenolic type antioxidants was implemented in this work. OIT dependences on holding temperature in the ranges of 180–200°С in oxygen environment and 200–220°С in the air were calculated. For selected experimental conditions (air oxidizing environment, the sample thickness of 650±100 microns and the holding temperature of 210°С) the statistical estimation of accuracy was evaluated. Relative standard deviation of developed technique was shown not to exceed 7%.

Neurotoxic Effect of Myricitrin in Copper-Induced Oxidative Stress Is Mediated by Increased Intracellular Ca2+ Levels and ROS/p53/p38 Axis.

Although commonly appreciated for their anti-oxidative and neuroprotective properties, flavonoids can also exhibit pro-oxidative activity, potentially reducing cell survival, particularly in the presence of metal ions. Disrupted copper homeostasis is a known contributor to neuronal dysfunction through oxidative stress induction. This study investigated the effects of myricitrin (1-20 μg/mL) on copper-induced toxicity (0.5 mM CuSO4) in the neuroblastoma SH-SY5Y cell line. At non-toxic concentrations, myricitrin exacerbated copper's toxic effects. The myricitrin-induced decrease in survival was accompanied with increased reactive oxygen species (ROS) production, reduced superoxide dismutase activity, and a lower GSH/GSSG ratio. In combination with copper, myricitrin also activated caspase-3/7, promoted nuclear chromatin changes, and compromised membrane integrity. At the protein level, myricitrin upregulated p53 and PUMA expression. The toxic effects of myricitrin were alleviated by the p38 inhibitor SB203580, the intracellular calcium chelator BAPTA-AM, and the NMDA receptor blocker MK-801, highlighting the significant role of the ROS/p53/p38 axis in cell death and the critical involvement of calcium ions in apoptosis induction. The atomic force microscopy was used to assess the surface morphology and nanomechanical properties of SH-SY5Y cells, revealing changes following myricitrin treatment. This research highlights the toxic potential of myricitrin and emphasizes the need for caution when considering flavonoid supplementation in conditions with elevated copper levels.

Characterization of Photo-Cross-Linked Polyethylene Pipes for Geothermal Energy Storage.

This study investigates the morphology and thermo-mechanical properties of cross-linked polyethylene (PEX) pipes for potential use in high-temperature borehole thermal energy storage systems. Particular attention is given to a novel type of PEX pipe produced through photoinitiated cross-linking (PEX-e). Two formulations, PEX-e1 and PEX-e2, were analyzed and compared to peroxide-cross-linked polyethylene (PEX-a) and non-cross-linked bimodal polyethylene (PE100) pipes. The degree of cross-linking was evaluated via gel content, while cross-link density and molecular weight between cross-links were determined using dynamic mechanical analysis (DMA). Phase composition and molecular mobility were explored through 1H static nuclear magnetic resonance (NMR), and the melting and crystallization behavior was assessed by differential scanning calorimetry (DSC). Oxidative stability and degradation were examined by using Fourier transform infrared (FTIR) spectroscopy, oxidation induction time (OIT) measurements, and thermogravimetric analysis (TGA). Both PEX-e formulations achieved satisfactory cross-linking degrees and exhibited remarkable OIT values. However, significant differences in cross-link distribution were noted, with PEX-e2 showing a less uniform dispersion of cross-links, which resulted in a lower storage modulus. FTIR analysis indicated that oxidation products were formed in PEX-e1 during cross-linking, highlighting the need for further optimization of the formulation and processing conditions.

Development of an extruded system with enhanced content of alpha-linolenic polyunsaturated fatty acid

The object of the study is the dependence of the technological indicators of the extruded system with an increased ALA content on the composition of the raw materials. The problem of the study is the need to increase the oxidative stability of the lipid component of extrudates, preserve their nutritional value and improve technological characteristics (in particular, porosity). An extruded system with an increased content of alpha-linolenic polyunsaturated fatty acid (ALA) based on a mixture of barley groats and flax seeds has been developed. The influence of flaxseed content on the technological parameters of model extruded systems, in particular porosity and oxidative stability of the lipid component, was studied. It was found that the rational content of flax seeds in the extrusion mixture is 7.0 %, providing the necessary porosity (80 %) and the induction period of accelerated oxidation at a temperature of 80 °C (10 hours). The proposed technological approach makes it possible to increase the shelf life of products while preserving nutritional value. The developed extruded system is promising for further implementation in the food industry, which will contribute to expanding the range of extruded products and increasing their market competitiveness. The effect of antioxidants – ascorbic and ferulic acids on the oxidative stability of lipids of the extruded system was studied: the content of ascorbic acid – 0.06...0.09 %, the content of ferulic acid – 0.10...0.15 %. The lipid component of the extruded system of the developed composition demonstrates a high level of oxidative stability (oxidation induction period – up to 22 hours). The obtained results indicate the possibility of using extruded systems with an increased ALA content to create specialized products with extended shelf life and reduced raw material costs

The Effect of Honey Powder Addition on Chosen Quality Properties of Model Chicken Products.

The objective of our paper was to evaluate the effect of honey powder addition on the quality of model chicken products over 14 days of refrigerated storage. Three model chicken product variants were produced: C-control, HP1%, HP2%-with 1 or 2% of honey powder addition. The cooking loss, basic chemical composition, water activity, texture, color, lipid oxidation (TBARS and PDSC), microbiological and sensory quality, and volatile compounds profile were determined. The adverse changes in lipids were slower in products with honey powder added compared to control product, revealing lower TBARS index values and longer oxidation induction times. After 14 days of storage, HP2% products showed significantly lower (up to 50%) TBARS values than control products. Furthermore, honey powder addition reduced the growth of psychrotrophic and lactic acid bacteria for up to 14 days of storage in comparison to the control products. However, deterioration of the volatile compounds profile (presence of alcohols and sulfur compounds) and occurrence of storage odor and flavor had an impact on the poorer sensory desirability of the control and HP1% products. Additional research is necessary aiming to improve the sensory quality of products with honey powder addition.

Modulating the Biliverdin Reductase (BVR)/ERK1/2 Axis to Attenuate Oxidative Stress in Rat Arterial Rings

Background: Biliverdin reductase (BVR) plays a central role in bile pigment metabolism by reducing biliverdin (BV) to bilirubin (BR), a potent antioxidant that scavenges reactive oxygen species (ROS) under normal and pathological conditions. Elevated oxidative stress activates extracellular signal-regulated protein kinases 1/2 (ERK1/2) signaling, which strongly interacts with BVR’s C and D motifs, forming the BVR/ERK1/2 axis. In pathological states, increased ERK1/2 activity inhibits BVR’s ability to convert BV to BR, exacerbating oxidative damage and contributing to cardiovascular disease. Therefore, the interaction between BVR and ERK1/2 is critical in modulating oxidative stress. Objectives: This study aimed to evaluate the effects of BR and the ERK1/2 inhibitor PD-98059, both individually and in combination, on ROS levels, ERK1/2 activity, and vascular responses under normoxic and hypoxia-reoxygenation (H-R) injury conditions. Methods: Aortic rings from rats were subjected to equal distending pressure after oxidative stress induction using 22'-Azobis (2-amidinopropane) dihydrochloride (ABAP) in an organ bath. Different doses of BR were administered in combination with the ERK1/2 inhibitor PD-98059 to assess their impact on ROS depletion, vascular relaxation, and maximal effect (Emax). Results: The combination of BR and PD-98059 significantly enhanced aortic relaxation and Emax under both normoxic and H/R conditions compared to either treatment alone. Inhibiting ERK1/2 with PD-98059 appeared to upregulate BVR activity, increasing BR synthesis and reducing oxidative damage in aortic rings. Conclusions: Biliverdin reductase plays a vital role in defending against oxidative stress and endothelial dysfunction through its dual-specificity kinase activity and interaction with ERK1/2. ERK1/2 inhibition further enhances BR’s ROS-scavenging ability and vascular protective effects. Targeting the interaction between BVR and ERK1/2 holds potential as an effective therapeutic strategy for conditions characterized by excessive ROS levels, such as cardiovascular diseases.

Synthesis of a novel starch-based emulsion gel with remarkable low-temperature stability via esterification, ozone-oxidation and ion induction.

A novel starch-based emulsion gel was designed via octenyl succinic anhydride (OSA) esterification, ozone oxidation, and ion (Ca2+) induction. The gel properties and low-temperature stability of emulsion gel with different oxidation time (0, 5, 10, 15, 25min; OW-0, 5, 10, 15, 25) were systematically investigated. FTIR revealed that the oxidation of CC and -OH groups in OW-0 by ozone oxidation led to their cleavage into carbonyl groups, and than transformed to carboxyl groups. Moreover, oxidation treatment changed the amorphous and crystal region of starch, resulting in the increasing extensibility, leaching of short chains, and charged groups. The presence of extended starch chains, leaching of short starch chains, and Ca2+ facilitated the formation of the promoting interaction between starch molecular chains, thereby developing a highly cross-linked network structure. Remarkably, a more compact gel network structure was formed through the interaction between water molecules and modified starch in the emulsion gel for OW-15. Furthermore, the gel network structure endowed the emulsion with thick, dense layers on the condensed surface, enhancing its stability at low temperatures. This research provides a novel strategy for designing the starch-based emulsion gel, holding promising applications in the food industry and other scientific fields.

The Antioxidative Role of Moringa Oil extract in Modulating Histological and Biochemical Changes in the Salivary Glands of Rats Under Oxidative Stress Induction

The Antioxidative Role of Moringa Oil extract in Modulating Histological and Biochemical Changes in the Salivary Glands of Rats Under Oxidative Stress Induction

Distribution of the p66Shc Adaptor Protein Among Mitochondrial and Mitochondria-Associated Membranes Fractions in Normal and Oxidative Stress Conditions.

p66Shc is an adaptor protein and one of the cellular fate regulators since it modulates mitogenic signaling pathways, mitochondrial function, and reactive oxygen species (ROS) production. p66Shc is localized mostly in the cytosol and endoplasmic reticulum (ER); however, under oxidative stress, p66Shc is post-translationally modified and relocates to mitochondria. p66Shc was found in the intermembrane space, where it interacts with cytochrome c, contributing to the hydrogen peroxide generation by the mitochondrial respiratory chain. Our previous studies suggested that p66Shc is localized also in mitochondria-associated membranes (MAM). MAM fraction consists of mitochondria and mostly ER membranes. Contact sites between ER and mitochondria host proteins involved in multiple processes including calcium homeostasis, apoptosis, and autophagy regulation. Thus, p66Shc in MAM could participate in processes related to cell fate determination. Due to reports on various and conditional p66Shc intracellular localization, in the present paper, we describe the allocation of p66Shc pools in different subcellular compartments in mouse liver tissue and HepG2 cell culture. We provide additional evidence for p66Shc localization in MAM. In the present study, we use precisely purified subcellular fraction isolated by differential centrifugation-based protocol from control mouse liver tissue and HepG2 cells and from cells treated with hydrogen peroxide to promote mitochondrial p66Shc translocation. We performed controlled digestion of crude mitochondrial fraction, in which the degradation patterns of p66Shc and MAM fraction marker proteins were comparable. Moreover, we assessed the distribution of the individual ShcA isoforms (p46Shc, p52Shc, and p66Shc) in the subcellular fractions and their contribution to the total ShcA in control mice livers and HepG2 cells. In conclusion, we showed that a substantial pool of p66Shc protein resides in MAM in control conditions and after oxidative stress induction.

In vitro assessment of the role of endoplasmic reticulum stress in sunitinib-induced liver and kidney toxicity

Sunitinib, a multi-targeted tyrosine kinase inhibitor, is prescribed for the treatment of metastatic gastrointestinal stromal tumors, advanced metastatic renal cell carcinoma, and pancreatic neuroendocrine tumors. Hepatotoxicity and nephrotoxicity are significant adverse effects of sunitinib administration; however, there is limited information regarding the molecular mechanisms of these adverse effects. The aim of the present study was to elucidate the role of endoplasmic reticulum stress in hepatotoxicity and nephrotoxicity induced by sunitinib. In addition to endoplasmic reticulum stress, oxidative stress and mitochondrial membrane potential were evaluated to investigate the molecular mechanism more comprehensively. Findings revealed that sunitinib exposure significantly increased the reactive oxygen species levels and decreased the Nrf2 gene expression and GSH/GSSG ratio, suggesting oxidative stress induction in normal hepatocyte (AML12) and normal kidney (HK-2) cell lines. Endoplasmic reticulum stress markers, including ATF4, CHOP, IRE1α, XBP1s and ATF6 mRNA expressions, were upregulated in AML12 cells. Furthermore, enhanced intracellular calcium levels also indicate endoplasmic reticulum stress in hepatocytes. In contrast, sunitinib exposure did not alter endoplasmic reticulum-related gene expression levels and intracellular calcium levels in HK-2 cells. In terms of mitochondrial membrane potential and caspase-3 activity, sunitinib induced mitochondrial membrane damage and increased caspase-3 activation not only in AML12 cells but also in HK-2 cells. The research findings indicate that sunitinib may induce cytotoxic effects in hepatocytes through mechanisms involving oxidative stress, endoplasmic reticulum stress, and mitochondrial damage. However, in the kidney, the toxicity mechanism is different from that of liver, and the endoplasmic reticulum stress does not seem to be involved in this mechanism.

Assessment of the Stability and Nutritional Quality of Hemp Oil and Pumpkin Seed Oil Blends.

This study characterized the quality of hemp oil (HO) and pumpkin seed oil (PO) and their blends before and after 2 and 4 months of storage at refrigerated and room temperature, without access to light and oxygen. The analyses included determining the acid value, peroxide value, fatty acid (FA) composition, and FA distribution in triacylglycerol (TAG) molecules. Pressure differential scanning calorimetry (PDSC) was used to assess the oxidative stability of oils and their blends. This study also evaluated the nutritional potential of hemp oil and pumpkin seed oil blends, as atherogenicity, thrombogenicity, and health-promoting indices and hypocholesterolaemic/hypercholesterolaemic ratio were calculated. The tested samples differed in properties depending on the storage time and temperature. The optimal choice was a blend of 50% hemp oil (HO) and 50% pumpkin oil (PO). This mixture demonstrated the desired fatty acid composition, satisfactory acid and peroxide values, and a relatively good oxidation induction time during storage. Despite the unfavorable distribution of FAs in TAG molecules, it was characterized by a balanced ratio of n-3 to n-6 acids. It was also concluded that research on HO and PO mixtures should be continued due to the potential synergistic effect of their bioactive substances.

Bioluminescent Whole-Cell Bioreporter Bacterial Panel for Sustainable Screening and Discovery of Bioactive Compounds Derived from Mushrooms.

This study presents a rapid and comprehensive method for screening mushroom extracts for the putative discovery of bioactive molecules, including those exhibiting antimicrobial activity. This approach utilizes a panel of bioluminescent bacteria, whose light production is a sensitive indicator of various cellular effects triggered by the extracts, including disruption of bacterial communication (quorum sensing), protein and DNA damage, fatty acid metabolism alterations, and oxidative stress induction. The bioassay's strength is its ability to efficiently analyze a large number of extracts simultaneously while also assessing several different mechanisms of toxicity, significantly reducing screening time. All samples analyzed exhibited more than one cellular effect, as indicated by the reporter bacteria. Four samples (C. cornucopioides, F. fomentarius, I. obliquus, and M. giganteus) displayed the highest number (six) of possible mechanisms of antibacterial activity. Additionally, combining extraction and purification protocols with a bioluminescent bacterial panel enables simultaneous improvement of the desired antimicrobial properties of the extracts. The presented approach offers a valuable tool for uncovering the diverse antimicrobial mechanisms of mushroom extracts.

Chemiluminescence-based evaluation of styrene block copolymers’ recyclability

The study presents the chemiluminescence based (CL) evaluation of the recyclability of linear styrene block copolymers. This analysis can provide insight into the material’s degradation state and predict its suitability for further recycling cycles, helping to avoid unnecessary energy consumption during processing.The thermal stability of four similar copolymer structures − styrene-isoprene-styrene (SIS), styrene-butadiene-styrene (SBS) copolymers with different styrene/butadiene ratios, and styrene-ethylene-butadiene-styrene (SEBS) − was studied using isothermal and non-isothermal chemiluminescence (CL). The activation energies for oxidative degradation were calculated based on oxidation induction times indicated by the CL intensities evolution. The results, which highlight the influence of molecular structure on stability under aging conditions, as presented by the calculated for the activation energy (kJ mol−1), show the following sequence: SBS (styrene 30%) (117 kJ mol−1) ≈ SIS 120 (kJ mol−1) < SBS (styrene 40%) (176 kJ mol−1) < SEBS (180 kJ mol−1). The CL data were correlated with infrared (IR) spectroscopy and differential scanning calorimetry (DSC) data, providing a comprehensive understanding of the thermal stability and degradation mechanisms during recycling proces. The sequence of the composing units determines the degradation process, with weaker points predominantly attacked in the linear moieties of isoprene, butadiene, and vinyl segments. The experimental data indicate that SIS and SBS (30% styrene) copolymers degrade the fastest likely due to the rapid accumulation of hydroperoxide radicals. The SEBS copolymer also experiences significant degradation, but this occurs at higher temperatures (above 220 ⁰C) and progresses more gradually once it begins. In contrast, the SBS copolymer with 40% styrene content degrades more slowly and exhibits minimal mass loss, primarily due to the formation of less reactive keto degradation products.

Influence of pharmacotherapy on function of biotransformation of xenobiotics liver in patients with neuropsychiatric disorders

BACKGROUND: The mechanisms of drug interactions of psychotropic drugs are associated with the processes of drug biotransformation by enzymes of microsomal oxidation of cytochrome P-450 in the liver. Various drugs can increase or decrease the activity of enzymes of the cytochrome P450-dependent system. AIM: To evaluate the effect of pharmacotherapy with psychotropic drugs: alprazolam, bromazepam, lithium carbonate on the metabolic rate of the model substrate antipyrine in saliva in patients with neuropsychiatric disorders; the effect of the enzyme-inducing activity of the original anticonvulsant 1-[(3-chlorophenyl)(phenyl)methyl]urea on the pharmacokinetic parameters of antipyrine in healthy volunteers. MATERIALS AND METHODS: 34 male patients were divided into three groups according to the nosological forms of diseases according to ICD-10: Group 1 — heading F43.23 and F43.25; 2 — F06.61; 3 — F41.2. Patients in the group 1 were prescribed alprazolam, in the 2 — bromazepam, in the 3 — lithium carbonate, for a course of 21 days. The comparison group consisted of 10 healthy volunteers. The original anticonvulsant was prescribed to the volunteers. Determination of the pharmacokinetics of antipyrine parameters as a test witness of the processes of elimination from the body was carried out in saliva before and after the end of therapy at a dose of 10 mg/kg once. RESULTS: Alprazolam administration by patients of group 1 at a dose of 0.5–1.5 mg/day for 21 days did not significantly affect the pharmacokinetic parameters of antipyrine: T1/2, Clt, AUC. Alprazolam did not change the elimination of antipyrine from the saliva of patients. In patients of the group2, who received bromazepam at a dose of 6–12 mg / day,a background decrease in T1/2, an increase in Clt, a decrease in AUC due to concomitant therapy were noted. Comparison of the pharmacokinetic parameters of antipyrine under the influence of bromazepam with background values not reveal significant differences. Therapy with lithium carbonate at a dose of 500–1000 mg/day in patients of the group 3 did not change the parameters of antipyrine elimination. The obtained data indicate that the drugs do not affect the activity of liver microsomal oxidation in patients. The study of the effect of 1-[(3-chlorophenyl)(phenyl)methyl]urea on the pharmacokinetic parameters of antipyrine in volunteers revealed a diametrically opposite result: a significant decrease in T1/2 by 2 times, an increase in Clt and a decrease in AUC, which indicates accelerated elimination of antipyrine from the saliva of the subjects and indicates the induction of liver microsomal oxidation. CONCLUSIONS: Pharmacotherapy using the studied psychotropic drugs in patients is not associated with the induction or inhibition of liver enzymes, which indicates the absence of drug pharmacokinetic interference. The original anticonvulsant 1-[(3-chlorophenyl)(phenyl)methyl]urea stimulated the induction of liver microsomal oxidation in volunteers.

Abstract 4137735: Chronic Oxidative Stress Induces Hypertension and Abdominal Aortic Aneurysm in Chemogenetic Mice Model

Background: Aortic aneurysms account for ~10,000 deaths annually in the USA. Oxidative stress is implicated in both abdominal (AAA) and thoracic (TAA) aneurysm formation, but the mechanisms are incompletely understood. We used a chemogenetic approach to modulate oxidative stress in the vascular wall by creating a transgenic mouse (DAAO-TG Tie2 ) that expresses yeast D-amino acid oxidase (DAAO) driven by the endothelial Tie2 promoter. DAAO generates the reactive oxygen species hydrogen peroxide from D-amino acids. Vascular tissues contain L-amino acids, so yeast DAAO is quiescent until DAAO-TG Tie2 mice are provided with D-amino acids. Here we characterize the cellular and molecular consequences of vascular oxidative stress in DAAO-TG Tie2 mice. Hypothesis: Chronic oxidative stress in the vascular wall causes arterial dysfunction. Aim: To characterize the phenotype of DAAO-TG Tie2 mice after oxidative stress induction in vascular endothelium. To identify the mechanisms whereby vascular oxidative stress causes arterial dysfunction and hypertension. Methods: Systolic blood pressure and aortic sonography were measured weekly in D-alanine-fed DAAO-TG Tie2 . Proteomic analyses were used to identify mechanistic targets, which were validated using biochemical and immunohistochemical methods. Results: D-alanine-fed DAAO-TG Tie2 mice develop systolic hypertension and abdominal but not thoracic aortic aneurysms; treated mice die in &gt;3 months with burst abdominal aortic aneurysms. Transgene expression is similar in abdominal and thoracic endothelium. Levels of oxidative stress markers (oxidized proteins, lipid, and DNA) were similar in thoracic and abdominal aorta. Proteomic analyses established phenotypic switching in abdominal but not thoracic aorta, and also revealed activation of the oxidant-activated kinase ASK1 and of the MAP kinase cascade in abdominal but not thoracic aorta. Immunoblot analyses showed a marked decrease in JNK1 phosphorylation by phosphatase DUSP3 and an increase in vascular KLF4, leading to phenotypic switching of contractile to synthetic VSMCs. Conclusion: Chronic chemogenetic oxidative stress induces hypertension and abdominal aortic aneurysm formation caused by KLF4-dependent VSMC phenotypic switching.

Accelerated Hydrothermal Aging and Degradation Mechanism of PE100 Butt-Fusion Welded Joint.

High-density polyethylene (HDPE) pipelines are extensively utilized in energy transportation in the ocean. However, long-term exposure to water can alter the performance of HDPE, potentially leading to pipeline accidents. This study focuses on simulating the aging characteristics of PE100 polyethylene pipeline butt-fusion welded joints (B-FWJs) in water using hydrothermal accelerated aging experiments at various temperature gradients. The performance of the B-FWJ after hydrothermal aging was characterized using scanning electron microscopy (SEM), oxidation induction time (OIT), attenuated total reflectance Fourier transform infrared (ATR FT-IR) spectroscopy, and mechanical testing. Furthermore, this study analyzed the performance characteristics and changes in the micro-molecular chains of an HDPE B-FWJ pipeline following hydrothermal aging. An investigation was conducted into the effects of hydrothermal aging temperature and duration on the physical and chemical characteristics of HDPE B-FWJ, and the aging mechanism under hydrothermal aging conditions was explored. The results indicate that increasing hydrothermal aging temperature leads to a more significant decrease in the mechanical properties of the B-FWJ. These findings contribute to understanding the aging behavior of PE100 pipelines in the joint section and offer insights to mitigate the risks associated with the aging of and damage to B-FWJ pipelines in the ocean.