Inhibition Of Lipid Peroxidation Research Articles

α -lipoic acid supplementation reduces oxidative stress and inflammation in red skeletal muscle of insulin-resistant rats

α -lipoic acid (ALA) is an eight-carbon saturated fatty acid with strong antioxidant activity. Despite previous reports of ALA's protective properties in treating cardiovascular and metabolic diseases (including insulin resistance and diabetes), little is known about the compound's effects on skeletal muscle metabolism. In particular, the effect of ALA on glycooxidative and nitrosative damage in red muscles during insulin resistance is unknown. This study investigated the therapeutic potential of ALA on the antioxidant barrier as well as oxidative, nitrosative and carbonyl stress in the red skeletal muscle of rats with high-fat diet-induced insulin resistance. Male Wistar cmdb/outbred rats were divided into four equal groups: control diet (CTRL), high fat diet (HFD), CTRL+ALA (30 mg/kg body weight for 4 weeks; intragastrically) and HFD+ALA. Enzymatic and nonenzymatic antioxidant systems, protein and lipid glycoxidation, nitrosative stress, and selected inflammatory/apoptosis parameters were assessed using colorimetric, fluorimetric, and immune-enzymatic methods. ALA lowered body weight and glucose metabolism parameters in insulin-resistant rats. ALA not only strengthened enzymatic antioxidant defense (by increasing superoxide dismutase, catalase and glutathione peroxidase activity) but also stimulated the synthesis of non-enzymatic GSH. ALA supplementation inhibited lipid peroxidation (decreased lipid hydroperoxides and malondialdehyde content) and prevented protein oxidation (by lowering advanced oxidation protein products concentration) in red muscle. ALA's multifactorial actions on muscle tissue also included inhibition of inflammation and apoptosis, requiring further research to elucidate its effects in metabolic diseases.

NFE2L2 and SLC25A39 drive cuproptosis resistance through GSH metabolism

Cuproptosis is a recently discovered form of regulated cell death triggered by mitochondrial copper accumulation and proteotoxic stress. Here, we provide the first evidence that glutathione (GSH), a major non-protein thiol in cells, acts as a cuproptosis inhibitor in pancreatic ductal adenocarcinoma (PDAC) cells. Mechanistically, GSH inhibits cuproptosis by chelating copper, contrasting its role in blocking ferroptosis by inhibiting lipid peroxidation. The classical cuproptosis inducer, ES-Cu (elesclomol plus copper), increases the protein stability of the transcription factor NFE2L2 (also known as NRF2), leading to the upregulation of gene expression of glutamate-cysteine ligase modifier subunit (GCLM) and glutamate-cysteine ligase catalytic subunit (GCLC). GCLM and GCLC are rate-limiting enzymes in GSH synthesis, and increased GSH is transported into mitochondria via the solute carrier family 25 member 39 (SLC25A39) transporter. Consequently, genetic inhibition of the NFE2L2-GSH-SLC25A39 pathway enhances cuproptosis-mediated tumor suppression in cell culture and in mouse tumor models. These findings not only reveal distinct mechanisms of GSH in inhibiting cuproptosis and ferroptosis, but also suggest a potential combination strategy to suppress PDAC tumor growth.

Seratrodast inhibits ferroptosis by suppressing lipid peroxidation

Ferroptosis is a regulated and non-apoptotic form of cell death mediated by iron-dependent peroxidation of polyunsaturated fatty acyl tails in phospholipids. Research of the past years has shed light on the occurrence of ferroptosis in organ injury and degenerative diseases of the brain, kidney, heart, and other tissues. Hence, ferroptosis inhibition may prove therapeutically beneficial to treat distinct diseases. In this study, we explored the ferroptosis-modulating activity of seratrodast, an inhibitor of thromboxane A2 (TXA2) receptor, which is approved in some countries for the treatment of asthma. Interestingly, seratrodast suppressed ferroptosis, but not apoptosis and necroptosis; thus, demonstrating selective anti-ferroptotic activity. While seratrodast itself does not inhibit lipid peroxidation, it exhibits potent radical-trapping antioxidant activity upon reduction to its corresponding hydroquinone form—analogously to ubiquinone and vitamin K. Importantly, seratrodast ameliorated the severity of renal ischemia-reperfusion injury in mice. Together, this study provides a drug repurposing case, where seratrodast—a marketed drug—can undergo fast-forward preclinical/clinical development for the inhibition of ferroptosis in distinct degenerative diseases.

Deficiency in glutathione peroxidase 4 (GPX4) results in abnormal lens development and newborn cataract

The human lens is composed of a monolayer of lens epithelial cells (LECs) and elongated fibers that align tightly but are separated by the plasma membrane. The integrity of the lens plasma membrane is crucial for maintaining lens cellular structure, homeostasis, and transparency. Glutathione peroxidase 4 (GPX4), a selenoenzyme, plays a critical role in protecting against lipid peroxidation. This study aims to elucidate the role of GPX4 in lens plasma membrane stability during lens development using in vitro, ex vivo, and in vivo systems. Our findings reveal that GPX4 deficiency triggers lens epithelial apoptosis-independent but ferroptosis-mediated cell death. Blocking lens GPX4 activity during ex vivo culture induces lens opacification, LEC death, and disruption of lens fiber cell arrangement. Deletion of lens-specific Gpx4 results in significant unsaturated phospholipid loss and an increase in oxidized phospholipids. Consequently, lenses with Gpx4 deficiency exhibit massive disruption of lens fiber cell structure, significant loss of LECs via ferroptosis, and formation of newborn cataracts. Remarkably, administering the lipid peroxidation inhibitor, liproxstatin-1, to pregnant mothers at embryonic days 9.5 significantly prevents lipid peroxidation, LEC death, and lens developmental defects. Our study unveils the crucial role of GPX4 in lens development and transparency, and also provides a successful intervention approach to prevent lens developmental defects through lipid peroxidation inhibition.

The Entourage Effect in Cannabis Medicinal Products: A Comprehensive Review.

This study explores the complementary or synergistic effects of medicinal cannabis constituents, particularly terpenes, concerning their therapeutic potential, known as the entourage effect. A systematic review of the literature on cannabis "entourage effects" was conducted using the PRISMA model. Two research questions directed the review: (1) What are the physiological effects of terpenes and terpenoids found in cannabis? (2) What are the proven "entourage effects" of terpenes in cannabis? The initial approach involved an exploratory search in electronic databases using predefined keywords and Boolean phrases across PubMed/MEDLINE, Web of Science, and EBSCO databases using Medical Subject Headings (MeSH). Analysis of published studies shows no evidence of neuroprotective or anti-aggregatory effects of α-pinene and β-pinene against β-amyloid-mediated toxicity; however, modest lipid peroxidation inhibition by α-pinene, β pinene, and terpinolene may contribute to the multifaceted neuroprotection properties of these C. sativa L. prevalent monoterpenes and the triterpene friedelin. Myrcene demonstrated anti-inflammatory proprieties topically; however, in combination with CBD, it did not show significant additional differences. Exploratory evidence suggests various therapeutic benefits of terpenes, such as myrcene for relaxation; linalool as a sleep aid and to relieve exhaustion and mental stress; D-limonene as an analgesic; caryophyllene for cold tolerance and analgesia; valencene for cartilage protection; borneol for antinociceptive and anticonvulsant potential; and eucalyptol for muscle pain. While exploratory research suggests terpenes as influencers in the therapeutic benefits of cannabinoids, the potential for synergistic or additive enhancement of cannabinoid efficacy by terpenes remains unproven. Further clinical trials are needed to confirm any terpenes "entourage effects."

Combining the Powerful Antioxidant and Antimicrobial Activities of Pomegranate Waste Extracts with Whey Protein Coating-Forming Ability for Food Preservation Strategies.

Different solvents water, ethanol and ethanol/water (6:4 v/v), were compared in the extraction of pomegranate peels and seeds (PPS) in terms of recovery yields, antioxidant properties, and antimicrobial action against typical spoilage bacterial and fungal species. The best performing extract (ethanol/water (6:4 v/v) was shown to contain mostly ellagic acid and punicalagin as phenolic compounds (5% overall) and hydrolysable tannins (16% as ellagic acid equivalents) and was able to inhibit the growth of the acidophilic Alicyclobacillus acidoterrestris at a concentration as low as 1%. The preservation of the organoleptic profile of A. acidoterrestris-inoculated apple juice with extract at 1% over 20 days was also observed thanks to the complete inhibition of bacterial growth, while the extract at 0.1% warranted a significant (40%) inhibition of the enzymatic browning of apple smoothies over the first 30 min. When incorporated in whey proteins' isolate (WPI) at 5% w/w, the hydroalcoholic extract conferred well appreciable antioxidant properties to the resulting coating-forming hydrogel, comparable to those expected for the pure extract considering the amount present. The WPI coatings loaded with the hydroalcoholic extract at 5% were able to delay the browning of cut fruit by ca. 33% against a 22% inhibition observed with the sole WPI. In addition, the functionalized coating showed an inhibition of lipid peroxidation of Gouda cheese 2-fold higher with respect to that observed with WPI alone. These results open good perspectives toward sustainable food preservation strategies, highlighting the potential of PPS extract for the implementation of WPI-based active packaging.

Photo-physical characterizations and evaluation of in-vitro antioxidant, anti-inflammatory and antidiabetic potentials of green synthesized ackee (Blighia sapida) selenium nano-particles

BackgroundGreen synthesized nanoparticles have recently gained significant medicinal applications and oftentimes outperform their green sources. Selenium is of fundamental importance to human health, stemming from its distinctive physicochemical properties, such as antioxidant activity, inhibition of Lipid peroxidation, stabilization of membrane proteins, maintenance of membrane fluidity and modulation of cell signaling. Though reports have shown some therapeutic potential of Ackee plant parts such as antioxidant, anti-inflammatory, antimicrobial, neuroprotective, very few scientific proofs still exist in support of these effects.MethodsThis study synthesized selenium nanoparticles (Se-NPs) from crude methanolic extracts of Ackee leaves (AKL) and Ackee arils (AKA), examined the photo-physical characteristics of the Se-NPs and determined the in-vitro antioxidant, antidiabetic, and anti-inflammatory potentials of AKL, AKA, and their Se-NPs using established protocols.ResultsIn both leaves and arils Se-NPs: UV spectroscopy revealed a qualitative absorbance at 310 nm; FTIR indicated multiple vibrations around 4000 cm−1- 400 cm−1; SEM images of 5 µm principally showed consistent size distribution of amorphous and granular shape at a magnification of 10,000X; while EDS spectra strongly confirm the presence of atomic Se compound at 30 kV. Various antioxidant activities assays carried out showed a range of approximately 4 to 60 times higher activities of the AKL, AKA, and Se-NPs than Ascorbic acid—the standard drug used. Furthermore, appreciable activities of more than 50% were obtained for alpha-amylase and alpha-glucosidase inhibitory activities, along with highly significant activities of haemoglobin glycosylation, glucose uptake, membrane stabilization, anti-arthritic, anti-haemolysis activities, when AKL, AKA, and Se-NPs were compared with standard drugs.ConclusionEncouraging the development and utilization of AKL, AKA, and Se-NPs will provide tremendous therapeutic efficacy and bioavailability approaches towards the management of diabetes, inflammation, and other oxidative stress-related diseases.

Evaluation of Cardioprotective Activity of <i>Corchorus aestuans</i> L. Leaves

Background: The effectiveness of several medicinal herbs with antioxidant qualities in MI has been assessed and demonstrated. Corchorus aestuans L. is one such medicinal plant that has been shown to have hypocholesteremic and antioxidant properties. C. aestuans L. is also well-known for its bitter tonic, cardiotonic, and stomach relieving properties. Aim: In order to assess the impact of C. aestuans methanol extract against ISO-induced changes in myocardial enzymes, antioxidant status, and cardiac pathology in experimentally induced myocardial infarction, this study was conducted. Methods: Male wistar albino rats were used to create an Isoproterenol (ISO) induced Myocardial Infarction (MI) in order to study the possible cardiovascular preventative effects of the methanol extract of the medicinal plant C. aestuans. Six groups of eight animals each were created from the 180-250 g range of animals, and during the study, the animals in groups one (normal control) and two (model control) were given distilled water. Group three received ascorbic acid (250 mg/kg), while groups four to six received methanol extract of C. aestuans (MECA; 50, 100, and 150 mg/kg, respectively) once a day for 28 days. Animals in group’s two to six received the first dosage of ISO (100 mg/kg, S.C.) on day 27 and the second dose 24 hours later. Rats were anesthetized using chloroform, then their hearts were isolated and serum was collected. Twelve hours following the second large dose, the rats anesthetized, killed, and samples of their hearts and serum were taken. After the heart was cleaned with ice-cold saline, it was weighed. A histology study was conducted on heart tissue, while biochemical markers were analyzed in serum and heart homogenate. Results: When isoproterenol was administered, the concentrations of CK-MB (Creatinine Kinase - Myocardial Band), LDH (Lactate Dehydrogenase), and NA+ (Sodium) increased dramatically, but the concentrations of K+ (Potassium) and MDA (Malondialdehyde) dropped. The incidence of these alterations was dramatically decreased by ascorbic acid and MECA (Methanol extract of C. aestuans) treatment. Consequently, the cardioprotective effect can be explained by decreased levels of cardiac marker enzymes. Conclusion: MECA (50 mg / kg, 100 mg / kg and 150 mg /kg p.o. once for 28 days) attenuated serum enzymes and marker, increased tissue calcium and sodium levels, decreased potassium levels, and inhibited lipid peroxidation to significantly counteract the effect of experimentally induced MI.

Antioxidant characterization of fruits of the Family Cactaceae: Hylocereus undatus, Selenicereus megalanthus, and Hylocereus polyrhizus

In this study, the antioxidant capacity of the peel and pulp of three Pitaya species was investigated: Hylocereus undatus, Selenicereus megalanthus, and Hylocereus polyrhizus. The methods used include the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method, the thiobarbituric acid reactivity assay (TBARS) for inhibition of lipid peroxidation, and the Folin-Ciocalteau method for determination of total phenolic content. Regarding the TBARS results, the peel sample of 20% H. polyrhizus showed the highest antioxidant capacity in both solvents (water and alcohol) analyzed. Regarding the pulp, the H. undatus sample in the aqueous extract was the sample with the highest antioxidant potential (12.5%). In the ethanolic extract, the sample of H. polyrhizus pulp (25%) showed the highest antioxidant potential, as did the peel at a concentration of 20%. Using the DPPH method, the peel sample of the 5% aqueous extract of H. undatus can be highlighted with a greater antioxidant capacity. Regarding the pulp, the sample with the highest potential was the 20% H. undatus in the aqueous extract. In the ethanolic extract, the H. undatus samples from the peel and pulp showed the highest antioxidant potential with 25 and 50%, respectively. In terms of phenolic content, no significant difference was found between the peel samples, but among the pulp samples, H. undatus had the lowest concentration. It can be concluded that the different pitaya species exhibited significant antioxidant capacity, suggesting that pitaya consumption could potentially provide benefits to human health due to its bioactive compounds.

Phytochemical profile, antioxidant and contractile activity of plants extracts used by parturients to manage childbirth in Niger

The widespread use of herbal preparations during childbirth and postnatal care in some developing countries is generating interest in scientific research about their standardized use. This study aims to compare the phytochemical profiles, the antioxidant properties, and the contractile effects of plants used to manage the childbirth of seven samples of plants (bark of Acacia senegal (L.) Willd, leaves and bark of Sclerocarya birrea, leaves of Lawsonia inermis L, whole plant of Sesamum alatum, whole plant of Ceratotheca sesamoides Endl. and brak of Ficus platyphylla). Qualitative and quantitative phytochemical screening was carried out using HPTLC and colorimetric methods. Antioxidant activity was evaluated using DPPH, ABTS and FRAP methods. Enzyme inhibition was performed on lipid peroxidation (LPO) and 15-Lipoxygenase (15-LOX). The contractile effect of uterine smooth muscle in NMRI mice was assessed ex vivo. The screening revealed the presence of several phytoconstituents, such as tannins, flavonoids, coumarins, saponins, sterols, and triterpenes. The highest content of phenolic compounds and tannins, respectively 980.61 ± 0.60 and 764.80 ± 0.54 µg GAE/mg dE, were obtained with the ethanolic extract of bark of Sclerocarya birrea (eth‑Dn-e). The highest content of flavonoids (456.95 ± 0.89 µg QE/mg dE) was obtained with the ethanolic extract of Ceratotheca sesamoides (eth‑Y). The ethanolic extract of Ficus platyphylla bark (eth‑G) effectively reduced DPPH, with an IC50 of 1.46 ± 0.06 µg/mL. The highest ferric ion-reducing power was obtained with Sclerocarya birrea bark decoction (Da-Dn-e), (78.95 ± 5.74 mmol AAE/g). Ethanolic macerate of Acacia senegal bark (eth‑D) showed the lowest IC50 against 15-LOX at 32.18 µg/mL. The aqueous macerate of Ceratotheca sesamoides (Ma-Y) gave the highest percentage inhibition of LPO, at 62.07 ± 0.01 %. The highest uterine contraction at 10 mg/mL was 1.38 [A(cm)/uterus(cm)], obtained with ethanolic maceration of the whole plant of Ceratotheca sesamoides Endl. (eth‑Y). The traditional use of plants during childbirth could be linked to the antioxidant and/or uterotonic effects of phytoconstituents. These constitutes a scientific basis that could justify the use of these plants in the management of childbirth.

Exploring the Functional Potential of Breast Milk Protein Hydrolysates: Antiglycation, Antioxidant, Metal Chelation, and Lipid Peroxidation Activities

The formation of advanced glycation end products (AGEs) is a pivotal factor in the development of various age-related and diabetes associated pathophysiologies, including but not limeted to arthritis, Alzheimer’s disease, atherosclerosis and cataracts. Consequently, the prospect of inhibiting AGE formation emerges as a viable strategy to prevent or halt the advancement of diabetic complications. In the scientific literature, there is still a reluctance to produce bioactive peptides demonstrating antiglycation activity from breast milk. The breast milk protein was hydrolysed using trypsin for 240 min. The antiglycation, metal chelating activity, lipid peroxidation activity, and antioxidant activity of the peptides in the hydrolysates obtained after hydrolysis of human milk with trypsin enzyme were performed. The peptide diversity obtained after hydrolysis was determined by RP-HPLC. The breast milk hydrolysate was demonstrated significant antiglycation activity (IC50: 312.8 ± 12.1 µg/mL), antioxidant activity (61.8±4.58 mM AAE/µg peptide) , metal chelation activity (24.4%/μg peptide). The hydrolysate effectively inhibited lipid peroxidation (30.5±0.12%) compared to Trolox (51.2±0.3%). These findings highlight the potential of breast milk protein hydrolysates as a source of bioactive peptides with diverse health benefits. The present study offers valuable insights into utilizing human milk peptides as novel functional food components.

Ligand-Based Radical Reactivity of Metal Thiosemicarbazones Prompts the Identification of Platinum(II)-Based Cytoprotectants.

CuATSM, a copper(II) complex of a bis(thiosemicarbazone) of diacetyl, prevents oxidative cell death and acts as a neuroprotectant in vivo, prompting its evaluation to treat amyotrophic lateral sclerosis and other neurodegenerative conditions in the clinic. We recently demonstrated that CuATSM functions as a potent radical-trapping antioxidant (RTA), inhibiting lipid peroxidation and associated ferroptotic cell death by a noncanonical mechanism based on radical addition to the ligand backbone. Herein we report our investigations of the generality of this reactivity, which include studies of corresponding complexes of various other metals, including Co, Ru, Ni, Pd, Pt, and Au. Inhibited autoxidations of styrene and dioxane reveal that most of these complexes exhibit RTA activity, consistent with ligand-based reactivity, but the identity of the metal atom nevertheless plays a role. In particular, analyses of the electronic structures of the complexes of metals within the same group (i.e., the group 10 metals Ni, Pd and Pt) highlight how the metal atom can modulate the ligand-based reactivity by enabling spin delocalization to the other thiosemicarbazone moiety. The RTA activity determined in organic solution largely translates to phospholipid bilayers and mammalian cells, where most complexes inhibited lipid peroxidation and associated ferroptotic cell death. A preliminary structure-activity study revealed Pt complexes with potencies eclipsing those of archetype ferroptosis inhibitors ferrostatin-1 and liproxstatin-1, suggesting that Pt (and to a lesser extent Ni) bis(thiosemicarbazone)s may be better suited to optimization for therapeutic development than those based on Cu.

Pathological Alterations in Heart Mitochondria in a Rat Model of Isoprenaline-Induced Myocardial Injury and Their Correction with Water-Soluble Taxifolin.

Mitochondrial damage and associated oxidative stress are considered to be major contributory factors in cardiac pathology. One of the most potent naturally occurring antioxidants is taxifolin, especially in its water-soluble form. Herein, the effect of a 14-day course of the peroral application of the water-soluble taxifolin (aqTAX, 15 mg/kg of body weight) on the progression of ultrastructural and functional disorders in mitochondria and the heart's electrical activity in a rat model of myocardial injury induced with isoprenaline (ISO, 150 mg/kg/day for two consecutive days, subcut) was studied. The delayed ISO-induced myocardial damage was accompanied by an increase in the duration of RR and QT intervals, and long-term application of aqTAX partially restored the disturbed intraventricular conduction. It was shown that the injections of ISO lead to profound ultrastructural alterations of myofibrils and mitochondria in cardiomyocytes in the left ventricle myocardium, including the impairment of the ordered arrangement of mitochondria between myofibrils as well as a decrease in the size and the number of these organelles per unit area. In addition, a reduction in the protein level of the subunits of the respiratory chain complexes I-V and the activity of the antioxidant enzymes catalase, glutathione peroxidase, and Mn-SOD in mitochondria was observed. The application of aqTAX caused an increase in the efficiency of oxidation phosphorylation and a partial restoration of the morphometric parameters of mitochondria in the heart tissue of animals with the experimental pathology. These beneficial effects of aqTAX are associated with the inhibition of lipid peroxidation and the normalization of the enzymatic activities of glutathione peroxidase and Mn-SOD in rat cardiac mitochondria, which may reduce the oxidative damage to the organelles. Taken together, these data allow one to consider this compound as a promising cardioprotector in the complex therapy of heart failure.

Method of intensification of digestive and intermediary metabolism in meat quails during denitrification

Sorbents are characterized by synergistic action with many biologically active compounds, including antioxidants that neutralize free radicals in the body, prevent membrane damage, and preserve the youth of the cells of organs and tissues of poultry. The purpose of the study was to determine the eff ect of the sorbent Mikosorb®A Plus and the antioxidant Hadox on the parameters of digestive and intermediary metabolism in meat quails when they are added to compound feed with a subtoxic dose of nitrates. It was found that in order to improve the digestive and intermediary metabolism in meat quails, the composition of their compound feed should include the drugs of the sorbent Mikosorb®A Plus at the dose of 1000 g/t and the antioxidant Hadox at the dose of 150 g/t of compound feed. These drugs allowed to increase signifi cantly (p < 0.05) the coeffi cients of dry matter digestibility by 3.43 abs.%, organic matter by 3.33 abs.%, crude protein by 3.55 abs.%, crude fi ber by 3.48 abs.% and nitrogen-free extractive substances by 3.57 abs.% in the quails of the 3rd experimental group compared to the control group. This also allowed to increase the number of erythrocytes in the blood of quails of the 3rd experimental group by 0.56×1012/l (p < 0.05), hemoglobin by 7.0 g/l (p < 0.05) with a simultaneous decrease in methemoglobin by 1.40 % (p < 0.05) compared to the control analogues. In the quails of the 3rd experimental group, the concentration of total protein in the blood serum was higher by 5.20 g/l (p < 0.05) with a simultaneous decrease in the content of nitrates by 1.63 times (p < 0.05) and nitrites by 2.47 times (p < 0.05) compared to the quails of the control group. Joint feeding of the sorbent and antioxidant inhibited lipid peroxidation processes and had a stimulating eff ect on the antioxidant defense mechanism in the quail body. At the same time, the quails of the 3rd experimental group had a lower proportion of conjugated dienes by 40.54 % and malondialdehyde by 28.72 % compared to the control group.

Reduced glutathione attenuates pediatric sepsis-associated encephalopathy by inhibiting inflammatory cytokine release and mitigating lipid peroxidation-induced brain injury.

Sepsis-associated encephalopathy (SAE) is a severe complication of sepsis. Reduced glutathione (GSH) has antioxidant properties and is used as a neuroprotective agent in some studies. However, research on the application of exogenous GSH in the treatment of SAE is limited. This study aimed to determine the effects of exogenous GSH in pediatric SAE patients and mice. We evaluated clinical parameters, inflammatory factors, and oxidative stress before and after GSH treatment. The clinical trials demonstrated that GSH treatment improved brain damage markers (S-100 beta protein, brain fatty acid-binding protein), increased neurological status scores (Glasgow coma scale), and reduced Pediatric Risk of Mortality III scores in children with SAE. GSH treatment also significantly reduced the levels of inflammatory factors (interleukin-6, tumor necrosis factor-α) and decreased lipid peroxidation (superoxide dismutase). Additionally, GSH reduced lipid peroxidation resulting from abnormal lipid metabolism, as indicated by the levels of acyl-CoA synthetase long-chain family member 4, lysophosphatidylcholine acyltransferase 3, and glutathione peroxidase 4. In-vivo experiments showed that the neuroprotective effect of GSH was dose-dependent, with better effects observed at medium and high doses. Furthermore, GSH alleviated brain damage, suppressed the release of inflammatory factors, and inhibited lipid peroxidation in SAE mice. The animal experiments also showed that GSH reduces lipid peroxidation through the 15-lipoxygenase/phosphatidylethanolamine binding protein 1/glutathione peroxidase 4 pathway. Our study suggests that exogenous GSH has neuroprotective effects in pediatric SAE. These findings provide a basis for the potential use of GSH as a therapeutic method for SAE.

Upregulation of PRRX2 by silencing Marveld3 as a protective mechanism against radiation-induced ferroptosis in skin cells.

Radiation-induced skin injury (RISI) represents a significant complication in patients receiving radiotherapy and individuals exposed to nuclear accidents, characterized by a protracted wound-healing process relative to injuries from other etiologies. Current preventive and management approaches remain inadequate. Consequently, investigating efficacious intervention strategies that target the disease's progression characteristics holds significant practical importance. Small interfering RNA (siRNA) and overexpression plasmid were used to modulate the expression of Marvel domain containing 3 (Marveld3) and paired related homeobox 2 (PRRX2). Protein and mRNA levels were estimated by Western Blot and real-time PCR, respectively. Intracellular levels of Malondialdehyde (MDA), a terminal product of lipid peroxidation, were measured following the manufacturer's protocol for MDA assay kit. Similarly, intracellular levels of ferrous iron (Fe2+) and reactive oxygen species (ROS) were determined using their respective assay kits. Lipid peroxidation status within the cells was evaluated via BODIPY staining. Immunohistochemistry was conducted to ascertain the expression of PRRX2 in skin tissues collected at various time points following irradiation of rats. The H-score method was used to evaluate the percentage of positively stained cells and staining intensity. RNA sequencing, Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted by OE Biotech Company. In this study, our findings indicated that Marveld3 suppression could effectively inhibit lipid peroxidation levels in irradiated skin cells, concomitantly reducing intracellular Fe2+ content. Additionally, the silencing of Marveld3 effectively abrogated the impact of a ferroptosis agonist on cellular viability, resulting in the upregulation of 66 and 178 genes, as well as the downregulation of 188 and 31 genes in irradiated HaCaT and WS1 cells, respectively. Among the differentially expressed genes, the PRRX2 which was found to be involved in the process of ferroptosis, exhibited statistically significant upregulation. And the upregulation of PRRX2 expression may attenuate radiation-induced lipid peroxidation in skin cells, thereby functioning as a potential stress-responsive mechanism to counteract radiation effects. This study elucidates the role of Marveld3 in radiation-induced ferroptosis in skin cells. Inhibition of Marveld3 led to the upregulation of PRRX2, which subsequently resulted in a reduction of Fe2+ and ROS levels, as well as the suppression of lipid peroxidation. These effects collectively mitigated the occurrence of ferroptosis.

Extremely Low-Frequency Electromagnetic Field (ELF-EMF) Increases Mitochondrial Electron Transport Chain Activities and Ameliorates Depressive Behaviors in Mice.

Compromised mitochondrial electron transport chain (ETC) activities are associated with depression in humans and rodents. However, the effects of the enhancement of mitochondrial ETC activities on depression remain elusive. We recently reported that an extremely low-frequency electromagnetic field (ELF-EMF) of as low as 10 μT induced hormetic activation of mitochondrial ETC complexes in human/mouse cultured cells and mouse livers. Chronic social defeat stress (CSDS) for 10 consecutive days caused behavioral defects mimicking depression in mice, and using an ELF-EMF for two to six weeks ameliorated them. CSDS variably decreased the mitochondrial ETC proteins in the prefrontal cortex (PFC) in 10 days, which were increased by an ELF-EMF in six weeks. CSDS had no effect on the mitochondrial oxygen consumption rate in the PFC in 10 days, but using an ELF-EMF for six weeks enhanced it. CSDS inactivated SOD2 by enhancing its acetylation and increased lipid peroxidation in the PFC. In contrast, the ELF-EMF activated the Sirt3-FoxO3a-SOD2 pathway and suppressed lipid peroxidation. Furthermore, CSDS increased markers for mitophagy, which was suppressed by the ELF-EMF in six weeks. The ELF-EMF exerted beneficial hormetic effects on mitochondrial energy production, mitochondrial antioxidation, and mitochondrial dynamics in a mouse model of depression. We envisage that an ELF-EMF is a promising therapeutic option for depression.

Effects of vitamin E on calcium signaling and oxidative injury in neutrophils of patients with ischemia/reperfusion (surgical arthroscopy) under sevoflurane anesthesia

Sevoflurane is an anesthetic, and it acts on oxidative activity by activating Ca2+ influx. In human neutrophils, oxidative stress activates the voltage-gated calcium channels (VGCC) and the TRPM2 channel; on the other hand, these channels are inhibited by 2-aminoethoxydiphenyl borate (2-APB) and verapamil plus diltiazem (V+D), respectively. Under sevoflurane anesthesia, surgical arthroscopy poses a significant risk to oxidative stress and Ca2+ influx-induced neutrophil infiltration and injury of patients. However, vitamin E may inhibit lipid peroxidation (LP) by upregulating reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) but downregulating TRPM2 and VGCC in the neutrophils of surgical arthroscopy patients. This topic was examined in the current study. We enrolled 20 patients in the current study, separating them into two primary groups: patients and patients plus vitamin E. Ten patients were divided into two groups: preoperative (N1) and postoperative (N2), both of which were not given vitamin E therapy. The remaining ten patients were given 300 IU of vitamin E two hours prior to their surgical arthroscopy (E1), and their blood was again drawn following the procedure (E2). Prior to fMLP stimulation, the isolated neutrophils from each of the four groups were cultured with 10 uM V+D and 100 uM 2-APB. In the neutrophils, there was an increase in intracellular free Ca2+ ([Ca2+]i) concentration and LP levels due to the downregulation of GSH and GSH-Px; however, following vitamin E treatment, GSH concertation and GSH-Px activity increased in the E2 group. While 2-APB and V+D treatment reduced the concentration of [Ca2+]i in the neutrophils, vitamin E administration had no effect on this measurement. In summary, vitamin E treatment mitigated the GSH and GSH-Px alterations induced by I/R damage, while TRPM2 and VGCC inhibition reduced the [Ca2+]i rise induced by I/R injury. One potential treatment approach for I/R-induced oxidative neutrophil damage is the suppression of TRPM2 and VGCC.

Benzyl Isothiocyanate Loaded Gelatin Nanoparticles Display Unique in Vitro Antioxidant Prospects

This present investigation focuses on the fact that nanoformulation of phytochemicals could enhance the therapeutic capacity in different physiological systems by enhancing hydrophilicity and bioavailability. In this study gelatin nano-formulation of benzyl isothiocyanate (BITC) was prepared and characterized by dynamic light scattering and UV-Visible spectrometry. Then antioxidant activity of BITC and BITC-gelatin NPs was determined in different concentrations through measuring 2,2- diphenyl-1- picrylhydrazyl (DPPH), superoxide, hydroxyl radical, nitric oxide scavenging and lipid peroxidation inhibition activities. DLS and UV-Vis study revealed the production of uniform nanosized particles and effective encapsulation of BITC respectively. The results of antioxidant assays suggested that BITC-gelatin NPs more effectively scavenged free radicals and inhibited lipid peroxidation compared to free BITC. The findings proposed that gelatin formulated BITC nanoparticles could be effective against oxidative stress related disorders.

Hyaluronic acid-functionalized carboxymethyl dextran-coated melatonin nanoconjugates for targeted etoposide delivery in metastatic colon cancer: Extensive in-vitro investigation in HCT116 cell lines, antimicrobial efficacy, and anti-angiogenic potential in chick chorioallantoic membrane (CAM) assay

Managing advanced colon cancer is challenging, requiring targeted therapies. This study presents a novel nanoconjugate system, HA-CMD@ETP-MLT-NCs, designed to deliver etoposide (ETP) specifically to colon cancer cells. The system consists of Hyaluronic Acid (HA)-Functionalized Carboxymethyl Dextran (CMD) coated with Melatonin (MLT). The nanoconjugates showed good stability, with a zeta potential of −29.90 mV and a particle size of 199.1 nm. They achieved an 80.3 % yield and a high drug entrapment efficiency of 93.4 %. In vitro release studies demonstrated pH-dependent drug release, with 73.4 % released at pH 5.5 (tumour-like environment) and 42.6 % at pH 7.4 (normal tissue) over 24 h. The nanoconjugates improved cellular uptake, induced apoptosis, and reduced reactive oxygen species (ROS) in HCT116 colon cancer cells. Flow cytometry showed a significant decrease in ROS levels, and lipid peroxidation inhibition increased to 56.67 %. These findings suggest that HA-CMD@ETP-MLT-NCs enhance etoposide delivery and reduce side effects. Further in vivo studies and clinical trials are needed to confirm its therapeutic potential.