Rate Of Peroxidation Research Articles

Methylene Blue-Mediated Photodynamic Therapy in Combination With Doxorubicin: A Novel Approach in the Treatment of HT-29 Colon Cancer Cells

Introduction: With an alarmingly growing number of patients diagnosed with colorectal cancer, adopting innovative anti-cancer approaches has recently garnered great attention. One interesting concept is the co-administration of cytotoxic agents and safer modalities such as photodynamic therapy (PDT), which can subsequently improve therapeutic efficacy and potentially reduce the risks of severe adverse effects and drug resistance. In the course of PDT, a locally injected photosensitizer (PS) is irradiated with a light source, which subsequently generates reactive oxygen species (ROS) and induces programmed cell death in tumor cells. Methods: In this study, to evaluate the potential anti-cancer effects of chemotherapy combined with PDT, in comparison to each alone, we employed PDT, comprising methylene blue (MB) and diode lasers at 630 and 810 nm wavelengths, in conjunction with the chemotherapeutic agent doxorubicin (DOX). Results: The MTT assay showed that the viability of colorectal cancer HT-29 cells decreased significantly following DOX+PDT treatment. Similarly, lactate dehydrogenase (LDH) release and lipid peroxidation rates were substantially higher in DOX+PDT treatment groups. Lastly, the catalase (CAT) assay indicated that the combination reduced the ability of CAT in the detoxification of H2 O2 . Conclusion: Our study suggests that MB-mediated PDT combined with chemotherapy might provide a promising avenue to improve therapeutic efficacy and potentially reduce the risk of adverse effects and drug resistance. Without a doubt, further investigations need to delve into the pharmacological advantages and disadvantages of PTD-based combination therapy and optimize its administered doses along with other modalities.

Novel Anthraquinone Derivatives and Their Complexes with Metal Ions with Anticancer Activity: Structure/Redox and Chelation Activity Correlations.

Background/Objectives: Some specific anthraquinone derivatives (AQs) are known to be used widely as effective chemotherapeutic agents in the treatment of cancer. However, their fundamental shortcoming is the high rate of cardiotoxicity observed in treated patients, which is thought to be caused by the increase in production of reactive oxygen species (ROS) catalyzed by iron and copper. The development of improved AQs and other anticancer drugs with enhanced efficacy but reduced toxicity remains a high priority. The aim of this study was to evaluate the cytotoxic and ROS production effects of chelate iron and copper complexes of two novel AQs, namely 4-hydroxynaphto[2,3-h]cinnoline-7,12-dione (Q2) and 3-(hydroxymethyl)naphto[2,3-h]cinnoline-4,7,12(1H)-trione (Q3). Methods: The chelation ability of Q2 and Q3 was studied using NMR and UV-Vis spectroscopy. Cytotoxicity studies were carried out using the MTT assay. The influence of chelation on ROS production was studied using NMR spectroscopy in linoleic acid micelles. Results: It was found that only Q3 forms complexes with Fe(III) and Cu(II) ions, whereas Q2 does not demonstrate chelating properties. A cytotoxicity study revealed that Fe[Q3]3 significantly decreased the viability of lung cancer A549 cells, while Q3 and Cu[Q3]2 did not demonstrate cytotoxic properties in this cell line. Furthermore, the presence of Q3 lowered the rate of iron-induced lipid peroxidation in linoleic acid micelles. By contrast, Q2 did not influence the rate of lipid peroxidation, probably due to the absence of effective metal chelating ability. Conclusions: The high cytotoxic effects observed with the iron complex of Q3 against cancer cells in combination with a reduced rate of iron induced lipid peroxidation in the presence of Q3, make Q3 and its iron complex promising for further evaluation and use as chemotherapeutic agents in cancer.

Simulation and optimization of heavy fuel oil (HFO) refining platform to low sulfur marine fuel (LS-FO) by oxidative desulfurization

The International Maritime Organization (IMO) has implemented new sulfur content regulations for marine fuels in response to growing environmental concerns, including global warming. These regulations severely and costly restrict refinery operations. Oxidative desulfurization (ODS) is an attractive desulfurization method that has advantages such as mild operating conditions and a hydrogen-free process over traditional processes such as hydrodesulfurization (HDS). One can employ oxidative desulfurization in addition to or instead of hydrodesulfurization. Organic sulfur molecules undergo oxidative desulfurization, which results in the formation of polar sulfones. The refined fuel oil is then separated from the oxidized sulfones using methods such liquid-liquid extraction, distillation, and absorption. This work examines and simulates the process of separating sulfur-containing oxidized chemicals from fuel oil utilizing oxidative desulfurization technology. Acetic acid served as the catalyst and hydrogen peroxide as the chosen oxidant. This effort involved simulating the oxidative desulfurization of fuel oil and then using absorption methods to separate the oxidized sulfones. Subsequent procedures including absorption and distillation were used to separate and recover the resultant effluent, solvent, and oxidant from the remaining components. According to the simulation results, the procedure was run at 80 °C and a modest pressure of less than 5 bar. Sulfur content in the original hydrocarbon fuel was 3.5% by weight; at the output, it was less than 0.5% by weight. The findings of the sensitivity analysis of a few key factors demonstrated that the conversion percentage increased from 84 to 98% when the reactor’s diameter was changed from 0.5 to 1.2 m and its length was extended to the desired amount. The reaction conversion percentage has increased significantly when the mass flow rate of hydrogen peroxide is increased from 0.5 to 1.5 kg/h, the pressure is increased from 1.5 to 5 bar, and the temperature is raised to 30 °C. According to the process optimization data, the ideal state had an exergy efficiency of 55.57%, a solvent waste rate of 1.75%, and a sulfur content of 0.22% in the fuel.

Effect of Shilajit on Freezing Rooster Semen

Reactive oxygen species (ROS) are created in excess during the cryopreservation process, which speeds up the rate of lipid peroxidation (LPO). This negatively impacts spermatozoa functions and reduces their capacity to fertilize. The spermatozoon plasma membrane consists of significant amounts of polyunsaturated fatty acids (PUFA), which can be easily oxidized by ROS and produce harmful agents that are toxic to cells. The plasma membrane of rooster spermatozoa contains high concentrations of polyunsaturated fatty acids and very small amounts of mitochondria, cytoplasm, and cytoplasmic antioxidants. Cryopreservation of rooster semen has been associated with adverse effects, including increased lipid peroxidation, structural damage in the mitochondria and acrosomal area, changes in the integrity and permeability of the spermatozoon plasma membrane, and severe damage to DNA. In the study, semen taken from 20 Plymouth Rock roosters were pooled to eliminate individual differences. By adding 5 μg/mL, 10 μg/mL, 15 μg/mL, 20 μg/mL and 25 μg/mL shilajit to Beltsville Poultry Semen Extender diluent, 5 experimental and 1 control groups were formed and frozen in 0.25 mL straws. After thawing in a water bath at 37oC, spermatologic parameters were analyzed with the CASA system. Viability evaluations were made with eosin – nigrosin stain and morphological evaluations were made with Hancock method. Sperm DNA integrity was examined with the COMET assay. As a result, it was concluded that the addition of 10, 15, 20 μg/mL shilajit to rooster semen extender improves semen quality parameters and DNA integrity of semen after cryopreservation.

Identification of Reactive Oxygen Species Genes Mediating Resistance to Fusarium verticillioides in the Peroxisomes of Sugarcane

Pokkah boeng disease (PBD), which is caused by Fusarium verticillioides, is a major sugarcane disease in Southeast Asian countries. Breeding varieties to become resistant to F. verticillioides is the most effective approach for minimizing the damage caused by PBD, and identifying genes mediating resistance to PBD via molecular techniques is essential. The production of reactive oxygen species (ROSs) is one of a cell’s first responses to pathogenic infections. Plant peroxisomes play roles in several metabolic processes involving ROSs. In this study, seedlings of YT94/128 and GT37 inoculated with F. verticillioides were used to identify PBD resistance genes. The cells showed a high degree of morphological variation, and the cell walls became increasingly degraded as the duration of the infection increased. There was significant variation in H2O2 accumulation over time. Catalase, superoxide dismutase, and peroxidase activities increased in both seedlings. Analysis of differentially expressed genes (DEGs) revealed that peroxidase-metabolism-related genes are mainly involved in matrix protein import and receptor recycling, adenine nucleotide transport, peroxisome division, ROS metabolism, and processes related to peroxisomal membrane proteins. The expression levels of SoCATA1 and SoSOD2A2 gradually decreased after sugarcane infection. F. verticillioides inhibited the expressions of C5YVR0 and C5Z4S4. Sugarcane infection by F. verticillioides disrupts the balance of intracellular ROSs and increases the cell membrane’s lipid peroxidation rate. Defense-related enzymes play a key regulatory role in maintaining a low, healthy level of ROSs. The results of this study enhance our understanding of the mechanism through which peroxisomes mediate the resistance of sugarcane to PBD and provide candidate genes that could be used to breed varieties with improved traits via molecular breeding.

Physicochemical Characterization and Thermodynamic Analysis of Avocado Oil Enhanced with Haematococcus pluvialis Extract

The consumption of fatty acids offers significant health benefits; however, they are prone to degradation by environmental factors. One method to preserve these fatty acids is the addition of synthetic antioxidants. This study focuses on the determination of peroxide and MDA formation rates at temperatures of 25 °C, 45 °C, and 65 °C. The oxidative stability of cold-pressed avocado oil was evaluated using pure astaxanthin, TBHQ, and H. pluvialis extract at concentrations of 100, 500, and 1000 ppm. Kinetic models and thermodynamic analysis were applied to determine the oxidation rate and compare the antioxidant effects of H. pluvialis extract with astaxanthin and TBHQ. The Arrhenius model was used to estimate activation energy (Ea), enthalpy, entropy, and free energy. Avocado oil with 500 ppm of H. pluvialis extract showed antioxidant effects comparable to TBHQ and pure astaxanthin. The activation energy of plain avocado oil was 40.47 kJ mol−1, while with H. pluvialis extract, it was 54.35 kJ mol−1. These findings suggest that H. pluvialis extract offers effective antioxidant properties and could serve as a natural alternative to synthetic antioxidants in food applications, despite the limitations of unprotected astaxanthin.

The Role of Inducible Nitric Oxide Synthase in Assessing the Functional Level of Coronary Artery Lesions in Chronic Coronary Syndrome.

Chronic coronary syndrome (CCS) is a long-term manifestation of coronary artery disease, marked by stable but recurring chest pain and myocardial ischemia due to the gradual buildup of atherosclerotic plaques in the coronary arteries. It is a metabolic disorder of coronary arteries characterized by oxidative stress, endothelial dysfunction, inflammation, and hyperlipidemia. The imbalance in oxidative-antioxidative status contributes to stable ischemic heart disease. Oxidative stress involves reactive oxygen and nitrogen species, leading to low-density lipoprotein (LDL) oxidation. Endothelial dysfunction, marked by reduced nitric oxide (NO) bioavailability, is an early onset of CCS, affecting vasodilation, cell proliferation, and inflammatory responses. Enzyme myeloperoxidase (MPO), traditionally considered protective, plays a dual role in initiating and progressing inflammatory diseases. MPO interacts with NO, modulating its catalytic activity. Elevated NO levels inhibit MPO through a reversible complex formation, preventing NO-induced inhibition by inducible nitric oxide synthase (iNOS). MPO also inactivates endothelial nitric oxide synthase (eNOS) and reacts with L-arginine, hindering NO synthesis. The interplay between MPO and NO significantly influences inflammation sites, impacting peroxidation rates and oxidation reactions. Peroxynitrite, a reactive species, contributes to nitration of tyrosine residues and lipid peroxidation. Mechanistic pathways suggest MPO enhances iNOS catalytic activity, influencing CCS development. iNOS, implicated in inflammation and atherosclerosis, is connected to NO regulation. This review analyzes the complex interplay of MPO, iNOS, and NO that affects plaque morphology, oxidative stress, and inflammation, contributing to atherosclerosis progression. Therefore, it is possible that the phenotypes of atherosclerotic plaques, focal and diffuse coronary artery disease, could be defined by the relationship between MPO and iNOS.

Guar gum and essential oil-based composite coatings preserve antioxidant enzymes activity and postharvest quality of kinnow Mandarin

Kinnow mandarin is a perishable fruit and is prone to various postharvest losses during storage and transportation. To address this issue, the effect of composite coatings of guar gum (GG) and lemongrass essential oil (LGO) on the quality and longevity of Kinnow mandarins was investigated. The findings showed that as compared to uncoated fruits, the GG 1.0% + LGO 1.0% coated fruits had less spoilage (3.01%), weight loss (7.21%), and lipid peroxidation rate (1.10 mmol g−1) while retaining higher levels of ascorbic acid, sensory quality, total soluble solids, flavonoids, and total antioxidant activity at the end of storage. The coated fruits also exhibited higher enzymatic activities of the superoxide dismutase (42.65 U min−1 g−1), phenylalanine ammonia-lyase (224 U h−1 g−1), peroxidase (35.21 U min−1 g−1), and catalase (47.65 U min−1 g−1). Furthermore, scanning electron microscopy (SEM) revealed a smooth and even layer in the composite-coated fruits, whereas uncoated fruits showed open stomata and cracks. These results indicate that coatings made of GG 1.0% and LGO 1.0% have the potential to preserve the qualitative features of Kinnow fruits stored at low temperatures.

The decomposition rate and bleaching efficacy of in-office bleaching gels with different pHs: a randomized controlled trial.

To evaluate the decomposition rate of active hydrogen peroxide (HP) and bleaching efficacy during in-office bleaching using high-concentration HP gels with different pHs. A randomized, parallel, double-blind controlled trial was conducted with 40 volunteers randomized into four groups (pH 5.4; pH 7.0; pH 7.7, and pH 8.0). During the first session in-office bleaching, approximately 0.01g of the gel was collected and titrated with potassium permanganate to obtain the concentration of active HP and pH values were measured using an electrode. Bleaching efficacy was assessed using a spectrophotometer [∆Eab, ∆E00, and WID], Vita Classical and Vita Bleachedguide scales [∆SGU]. The decomposition rate of HP concentration and pH values change were calculated using ANOVA one-way. The bleaching efficacy was assessed using two-way repeated measures ANOVA. Tukey's test was applied as a post-hoc test (p < 0.05). All gels experienced decreasing HP concentration over time. pH 5.4 gel showed greatest reduction after 50min (p < 0.001). pH 8.0 and 7.7 gels remained stable; pH 5.4 remained acidic, while pH 7.0 turned acidic (p < 0.001). No significant difference in bleaching degree was observed among gels. They all showed a similar and clinically important color change after two clinical sessions, remained stable 1-month post-treatment (p > 0.05). All bleaching gels kept at least 70% of their HP content after 50min, suggesting that there is a surplus of HP. They provided similar whitening efficacy 1-month after bleaching. It is possible that lower HP concentrations may be equally effective in achieving desired results while reducing the potential for side effects. RBR-35q7s3v.

Tauroursodeoxycholic Acid (TUDCA) Relieves Streptozotocin (STZ)-Induced Diabetic Rat Model via Modulation of Lipotoxicity, Oxidative Stress, Inflammation, and Apoptosis.

Tauroursodeoxycholic acid (TUDCA) is approved for the treatment of liver diseases. However, the antihyperglycemic effects/mechanisms of TUDCA are still less clear. The present study aimed to evaluate the antidiabetic action of TUDCA in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) in rats. Fifteen adult Wistar albino male rats were randomly divided into three groups (n = five in each): control, diabetic (STZ), and STZ+TUDCA. The results showed that TUDCA treatment significantly reduced blood glucose, HbA1c%, and HOMA-IR as well as elevated the insulin levels in diabetic rats. TUDCA therapy increased the incretin GLP-1 concentrations, decreased serum ceramide synthase (CS), improved the serum lipid profile, and restored the glycogen content in the liver and skeletal muscles. Furthermore, serum inflammatory parameters (such as TNF-α, IL-6, IL-1ß, and PGE-2) were substantially reduced with TUDCA treatment. In the pancreas, STZ+TUDCA-treated rats underwent an obvious enhancement of enzymatic (CAT and SOD) and non-enzymatic (GSH) antioxidant defense systems and a marked decrease in markers of the lipid peroxidation rate (MDA) and nitrosative stress (NO) compared to STZ-alone. At the molecular level, TUDCA decreased the pancreatic mRNA levels of iNOS and apoptotic-related factors (p53 and caspase-3). In conclusion, TUDCA may be useful for diabetes management and could be able to counteract diabetic disorders via anti-hyperlipidemic, antioxidant, anti-inflammatory, and anti-apoptotic actions.

Basidiomycetes Polysaccharides Regulate Growth and Antioxidant Defense System in Wheat.

Higher-fungi xylotrophic basidiomycetes are known to be the reservoirs of bioactive metabolites. Currently, a great deal of attention has been paid to the exploitation of mycelial fungi products as an innovative alternative in crop protection. No data exist on the mechanisms behind the interaction between xylotrophic mushrooms' glycopolymeric substances and plants. In this study, the effects of basidiomycete metabolites on the morphophysiological and biochemical variables of wheat plants have been explored. Wheat (Triticum aestivum L. cv. Saratovskaya 29) seedlings were treated with extracellular polysaccharides (EPSs) isolated from the submerged cultures of twenty basidiomycete strains assigned to 13 species and 8 genera. The EPS solutions at final concentrations of 15, 40, and 80 mg/L were applied to wheat seedlings followed by their growth for 10 days. In the plant samples, the biomass, length of coleoptile, shoot and root, root number, rate of lipid peroxidation by malondialdehyde concentration, content of hydrogen peroxide, and total phenols were measured. The peroxidase and superoxide dismutase activity were defined. Most of the EPS preparations improved biomass yields, as well as the morphological parameters examined. EPS application enhanced the activities of antioxidant enzymes and decreased oxidative damage to lipids. Judging by its overall effect on the growth indices and redox system of wheat plants, an EPS concentration of 40 mg/L has been shown to be the most beneficial compared to other concentrations. This study proves that novel bioformulations based on mushroom EPSs can be developed and are effective for wheat growth and antioxidative response. Phytostimulating properties found for EPSs give grounds to consider extracellular metabolites produced in the xylotrophic basidiomycete cultures as an active component capable of inducing plant responses to stress.

A new biostimulant derived from soybean by-products enhances plant tolerance to abiotic stress triggered by ozone

BackgroundTropospheric ozone is an air pollutant that causes negative effects on vegetation, leading to significant losses in crop productivity. It is generated by chemical reactions in the presence of sunlight between primary pollutants resulting from human activity, such as nitrogen oxides and volatile organic compounds. Due to the constantly increasing emission of ozone precursors, together with the influence of a warming climate on ozone levels, crop losses may be aggravated in the future. Therefore, the search for solutions to mitigate these losses becomes a priority.Ozone-induced abiotic stress is mainly due to reactive oxygen species generated by the spontaneous decomposition of ozone once it reaches the apoplast. In this regard, compounds with antioxidant activity offer a viable option to alleviate ozone-induced damage. Using enzymatic technology, we have developed a process that enables the production of an extract with biostimulant properties from okara, an industrial soybean byproduct. The biostimulant, named as OEE (Okara Enzymatic Extract), is water-soluble and is enriched in bioactive compounds present in okara, such as isoflavones. Additionally, it contains a significant fraction of protein hydrolysates contributing to its functional effect.Given its antioxidant capacity, we aimed to investigate whether OEE could alleviate ozone-induced damage in plants. For that, pepper plants (Capsicum annuum) exposed to ozone were treated with a foliar application of OEE.ResultsOEE mitigated ozone-induced damage, as evidenced by the net photosynthetic rate, electron transport rate, effective quantum yield of PSII, and delayed fluorescence. This protection was confirmed by the level of expression of genes associated with photosystem II. The beneficial effect was primarily due to its antioxidant activity, as evidenced by the lipid peroxidation rate measured through malondialdehyde content. Additionally, OEE triggered a mild oxidative response, indicated by increased activities of antioxidant enzymes in leaves (catalase, superoxide dismutase, and guaiacol peroxidase) and the oxidative stress index, providing further protection against ozone-induced stress.ConclusionsThe present results support that OEE protects plants from ozone exposure. Taking into consideration that the promotion of plant resistance against abiotic damage is an important goal of biostimulants, we assume that its use as a new biostimulant could be considered.

Effect of distillers yeast in feed on texture, fatty acid profile and antioxidant properties of breast muscle of broiler chickens

This research aimed to assess the impact of replacing a partially of post-extraction soybean meal in the diet with varying amounts of distillers yeast (3, 6 and 9%) on the composition and quality in the pectoral muscles of broiler chickens. Findings revealed that cockerels fed with 3% yeast exhibited elevated oleic acid levels and reduced n-6 fatty acids compared to those fed with 6% and 9% yeast. Furthermore, chickens consuming 3% yeast displayed higher antioxidant capacity (ABTS) and decreased levels of linoleic acid and its ratio to α-linolenic acid compared to the 9% yeast group. Moreover, muscles from cockerels on the 3% yeast diet and the control group demonstratedhigher shear force, lower n-6/n-3 ratio and lipid peroxidation rate (TBARS) than those on the 9% yeast regimen. Conversely, cockerels on the 9% yeast diet exhibited reduced gumminess and ferric reducing antioxidant power (FRAP) compared to the control group. The study highlights yeast’s role in altering broiler chicken meat’s fatty acid profile, texture, and antioxidant properties.

The fate of intracellular S1P regulates lipid droplet turnover and lipotoxicity in pancreatic beta-cells

Lipotoxicity has been considered the main cause of pancreatic beta-cell failure during type 2 diabetes development. Lipid droplets (LD) are believed to regulate the beta-cell sensitivity to free fatty acids (FFA), but the underlying molecular mechanisms are largely unclear. Accumulating evidence points, however, to an important role of intracellular sphingosine-1-phosphate (S1P) metabolism in lipotoxicity-mediated disturbances of beta-cell function. In the present study, we compared the effects of an increased irreversible S1P degradation (S1P-lyase, SPL overexpression) with those associated with an enhanced S1P recycling (overexpression of S1P phosphatase 1, SGPP1) on LD formation and lipotoxicity in rat INS1E beta-cells. Interestingly, although both approaches led to a reduced S1P concentration, they had opposite effects on the susceptibility to FFA. Overexpression of SGPP1 prevented FFA-mediated caspase-3 activation by a mechanism involving an enhanced lipid storage capacity and prevention of oxidative stress. In contrast, SPL overexpression limited LD biogenesis, content, and size, while accelerating lipophagy. This was associated with FFA-induced hydrogen peroxide formation, mitochondrial fragmentation, and dysfunction, as well as ER stress. These changes coincided with the upregulation of proapoptotic ceramides but were independent of lipid peroxidation rate. Also in human EndoC-βH1 beta-cells, suppression of SPL with simultaneous overexpression of SGPP1 led to a similar and even more pronounced LD phenotype as that in INS1E-SGPP1 cells. Thus, intracellular S1P turnover significantly regulates LD content and size and influences beta-cell sensitivity to FFA.

Melatonin counteracts polyethylene microplastics induced adreno-cortical damage in male albino rats

There are various substances that can disrupt the homeostatic mechanisms of the body, defined as endocrine-disrupting chemicals (EDCs). The persistent nature of microplastics (MPs) is a cause for concern due to their ability to accumulate in food chains and widespread use, making their toxic effects particularly alarming. The potential of MPs for disrupting the endocrine system was observed in multiple tissues. Moreover, the adrenal gland is known to be extremely sensitive to EDCs, while with the effect of MPs on the adrenal gland has not previously been studied. This study aimed to highlight the potential polyethylene microplastics (PE-MPs) induced adreno-toxic effects rather than exploring the implicated mechanisms and concluding if melatonin (Mel) can afford protection against PE-MPs induced adreno-toxicity. To fulfill the goal, six groups of rats were used; control, Mel, PE-MPs (3.75 mg/kg), PE-MPs (15 mg/kg), PE-MPs (3.75 mg/kg) +Mel, and PE-MPs (15 mg/kg) +Mel. PE-MPs induced toxic changes in the adrenal cortex, which was evident by increased adrenal weight, histopathological examination, and ultrastructural changes detected by electron microscope. A reduction in serum cortisol and an increase in serum adrenocorticotropic hormone resulted from the adreno-toxic effects of PE-MPs. Mechanisms may include the reduction of steroidogenesis-related genes, as PE-MPs drastically reduce mRNA levels of StAR, Nr0b1, Cyp11A1, as well as Cyp11B1. Also, oxidative stress that results from PE-MPs is associated with higher rates of lipid peroxidation and decreased superoxide dismutase and glutathione. PE-MPs inflammatory effect was illustrated by elevated expression of IL-1β and NF-ķB, detected by immunohistochemical staining, in addition to increased expression of caspase-3 and mRNA of Bax, markers of proapoptotic activity. The impacts of PE-MPs were relatively dose-related, with the higher dose showing more significant toxicity than the lower one. Mel treatment was associated with a substantial amelioration of PE-MPs-induced toxic changes. Collectively, this study fills the knowledge gap about the MPs-induced adrenal cortex and elucidates various related toxic mechanisms. It also supports Mel’s potential protective activity through antioxidant, anti-inflammatory, anti-apoptotic, and gene transcription regulatory effects.

Photochromic radical states in 3D covalent organic frameworks with zyg topology for enhanced photocatalysis.

Covalent-organic frameworks (COFs) with photoinduced donor-acceptor (D-A) radical pairs show enhanced photocatalytic activity in principle. However, achieving long-lived charge separation in COFs proves challenging due to the rapid charge recombination. Here, we develop a novel strategy by combining [6+4] nodes to construct zyg-type 3D COFs, first reported in COF chemistry. This structure type exhibits a fused Olympic-rings-like shape, which provides a platform for stabilizing the photoinduced D-A radical pairs. The zyg-type COFs containing catalytically active moieties such as triphenylamine and phenothiazine (PTZ) show superior photocatalytic production rates of hydrogen peroxide (H2O2). Significantly, the photochromic radical states of these COFs show up to 400% enhancement in photocatalytic activity compared to the parent states, achieving a remarkable H2O2 synthesis rate of 3324 μmol g-1 h-1, which makes the PTZ-COF one of the best crystalline porous photocatalysts in H2O2 production. This work will shed light on the synthesis of efficient 3D COF photocatalysts built on topologies that can facilitate photogenerating D-A radical pairs for enhanced photocatalysis.

Mitochondrial Peroxiredoxin 6 Declines with Aging in Parallel with Increases in Hydrogen Peroxide Generation

Oxidative stress in cells and tissues arise from an imbalance between the generation of free radicals and the ability to detoxify these reactive oxygen species (ROS). Peroxiredoxins (PRDXs) are a family of widely distributed enzymes that act as master antioxidant regulators by scavenging peroxides and peroxynitrites. The accumulation of oxidative damage from chronic exposure to oxidative stress such as on DNA, mitochondrial proteins, and lipid macromolecules, is postulated to result in age-associated pathologies and physiological dysfunctions. Peroxiredoxin-6 (PRDX6) contributes to the maintenance of redox balance in a variety of tissues from lung to skeletal muscle. Here, we hypothesized that PRDX6 localizes to the mitochondria and plays a significant role in maintaining mitochondrial function through targeting mitochondrially generated ROS, and that gradual loss of mitochondrial PRDX6 contributes to increased oxidative stress and accumulation of oxidative damage during aging. In this study, respiratory rates and complex activities in isolated skeletal muscle mitochondria obtained from young (3-6 months) and old (20-24 months) C57/BL6J mice were compared. Amplex UltraRed fluorescence was used to determine production rates of mitochondrial hydrogen peroxide (H2O2). Western blot analysis was used to compare protein abundance and ELISA was used to measure lipid peroxidation in skeletal muscle mitochondrial fractions. Our findings revealed that isolated mitochondria from skeletal muscle in old mice generated higher rates of H2O2 from complex I (CI) during state 3 and state 4 (State 3; State 4) derived respiration (3.93 ± 0.41; 3.56 ± 0.38 pmol H2O2..s−1.mg−1) compared to young mouse mitochondria (1.57 ± 0.48; 1.89 ± 0.59 pmol H2O2.s−1.mg−1, p ≤ 0.05). This was also found when saturating amounts of ADP were used to stimulate maximal rates of oxygen consumption (old: 3.65 ± 0.77; young 1.40 ± 0.21 pmol H2O2−1.mg−1, p ≤ 0.05). Furthermore, CI activity was found to be lower in isolated mitochondria from old mice (0.65 ± 0.006 U.ug−1) compared to young mice (2.11 ± 0.64 U.ug−1, p ≤ 0.05). Similarly, mitochondrial PRDX6 abundance was lower while levels of lipid peroxidation product malondialdehyde were higher in skeletal muscle from old animals (old: 2712 ± 1320 pg.mL−1; young: 489 ± 225 pg.mL−1). These results show higher mitochondrial ROS generation rates and oxidative damage in old animals. These data also suggest that loss of PRDX6 in aging leads to mitochondrial dysfunction mediated by diminished CI activity and loss of membrane integrity. We are currently conducting mechanistic studies in cellular models with disrupted PRDX6 expression to confirm the effect of this protein in maintaining mitochondrial function. This study offers novel observations on the significance of mitochondrially localized PRDX6 in antioxidant defense as well as the sources and roles of ROS generation in contributing to an aging phenotype. National Institute of General Medical Sciences (NIGMS, Award Number R35GM146951). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Modeling ferroptosis in human dopaminergic neurons: Pitfalls and opportunities for neurodegeneration research

The activation of ferroptosis is being pursued in cancer research as a strategy to target apoptosis-resistant cells. By contrast, in various diseases that affect the cardiovascular system, kidneys, liver, and central and peripheral nervous systems, attention is directed toward interventions that prevent ferroptotic cell death. Mechanistic insights into both research areas stem largely from studies using cellular in vitro models. However, intervention strategies that show promise in cellular test systems often fail in clinical trials, which raises concerns regarding the predictive validity of the utilized in vitro models.In this study, the human LUHMES cell line, which serves as a model for human dopaminergic neurons, was used to characterize factors influencing the activation of ferroptosis. Erastin and RSL-3 induced cell death that was distinct from apoptosis. Parameters such as the differentiation state of LUHMES cells, cell density, and the number and timing of medium changes were identified as determinants of sensitivity to ferroptosis activation. In differentiated LUHMES cells, interventions at mechanistically divergent sites (iron chelation, coenzyme Q10, peroxidase mimics, or inhibition of 12/15-lipoxygenase) provide almost complete protection from ferroptosis. LUHMES cells allowed the experimental modulation of intracellular iron concentrations and demonstrated a correlation between intracellular iron levels, the rate of lipid peroxidation, as well as the sensitivity of the cells to ferroptotic cell death.These findings underscore the importance of understanding the various factors that influence ferroptosis activation and highlight the need for well-characterized in vitro models to enhance the reliability and predictive value of observations in ferroptosis research, particularly when translating findings into in vivo contexts.

Effects of Glyprolins on Lipid and Protein Peroxidation in the Hypothalamic Region in Experimental Hyperthyroidism

We investigate effects of glyproline-type neuropeptides on lipid and protein peroxidation in the hypothalamic brain region of rats under the conditions of experimental hyperthyroidism. The state of hyperthyroidism in animals was simulated by intragastric administration of sodium pentahydrate of L-thyroxine at a dose of 150 µg/kg for 21 days. The following experimental groups (n=10) were formed: 1) control group — intact animals (control); 2) animals treated with L-thyroxine sodium salt pentahydrate (hyperthyroidism); 3) animals treated with Thr-Lys-Pro-Arg-Pro-Gly-Pro (celank); 4) animals treated with Pro-GlyPro (doses of 87 and 33 µg/kg/day, respectively) intraperitoneally daily during 21 days starting one day after the last administration of sodium pentahydrate of L-thyroxine. The level of lipid peroxidation processes was assessed by the initial level of TBA-reactive products, spontaneous and ascorbate-dependent lipid peroxidation rates in hypothalamic tissue homogenate. Protein peroxidation products were determined by the reaction between oxidized amino acid residues of proteins and 2,4-dinitrophenylhydrazone. The enzymatic part of the antioxidant system of hypothalamic region was estimated by measuring the activity of superoxide dismutase and catalase. In the setting of Thr-Lys-Pro-Arg-Pro-Gly-Pro and Pro-Gly-Pro administration under experimental hyperthyroidism, the intensity of lipid and protein peroxidation processes was decreased, while the activity of antioxidant enzymes-superoxide dismutase and catalase was restored in the hypothalamic tissue. The experimental data obtained indicate that, under the conditions of experimental hyperthyroidism, Thr-Lys-Pro-Arg-Pro-Gly-Pro and Pro-Gly-Pro compounds exhibit an antioxidant and antiradical activity with respect to parameters of lipoperoxidation and oxidative modification of proteins, as well as with respect to enzymatic defense systems in the hypothalamic brain region of laboratory animals.

Biochemical Changes: Their Potential Role against Fungal Disease Resistance Development in Mustard

Rape-seed mustard is an imperative edible oilseed crop which is adversely affected by different biotic stresses causing import of edible oils from abroad. The experiment was carried out for screening mustard genotypes based on disease indexing and putative role of diverse biochemical parameters in development of resistant against three major fungal diseases. A modified 0-9 scale was used for rating of disease indicators to calculate disease incident (DI). In disease indexing, mustard genotypes L-4, GSC-7 and PC-6 were considered as immune against Alternaria brassicae, Maya, L-4, China, GSL-1, GSC-7, PC-5, PC-6 and RP-9 were classified as immune against Albugo candida while L-4 and PC-5 were found immune against Erysiphe cruciferarum. The study of biochemical constituents demonstrated that these immune genotypes accumulated higher osmolytes content including free proline content and total phenol under diseased condition showing their tolerance ability against these pathogens. The tolerant genotypes also had lesser lipid peroxidation rate as indicated by malondialdehyde content analysis to induce lesser effect on total chlorophyll, amino acids, proteins and soluble sugars including reducing and non-reducing sugars. These identified genotypes have wider scope for further phyto-pathological studies and utilization in development of fungal resistance breeding.