Lipid Peroxidation Products Research Articles

Redox Biomarkers and Matrix Remodeling Molecules in Ovarian Cancer.

Ovarian cancer (OC) has emerged as the leading cause of death due to gynecological malignancies among women. Oxidative stress and metalloproteinases (MMPs) have been shown to influence signaling pathways and afflict the progression of carcinogenesis. Therefore, the assessment of matrix-remodeling and oxidative stress intensity can determine the degree of cellular injury and often the severity of redox-mediated chemoresistance. The study group comprised 27 patients with serous OC of which 18% were classified as Federation of Gynecology and Obstetrics (FIGO) stages I/II, while the rest were diagnosed grades III/IV. The control group comprised of 15 ovarian tissue samples. The results were compared with genetic data from The Cancer Genome Atlas. Nitro-oxidative stress, inflammation and apoptosis biomarkers were measured colorimetrically/fluorometrically or via real-time PCR in the primary ovarian tumor and healthy tissue. Stratification of patients according to FIGO stages revealed that high-grade carcinoma exhibited substantial alterations in redox balance, including the accumulation of protein glycoxidation and lipid peroxidation products. TCGA data demonstrated only limited prognostic usefulness of the studied genes. In conclusion, high-grade serous OC is associated with enhanced tissue oxidative/nitrosative stress and macromolecule damage that could not be overridden by the simultaneously augmented measures of antioxidant defense. Therefore, it can be assumed that tumor cells acquire adaptive mechanisms that enable them to withstand the potential toxic effects of elevated reactive oxygen species.

Modifications of DAMPs levels in extracellular environment induced by aminolevulinic acid-based photodynamic therapy of esophageal cancer cells

Purpose Immunogenic cell death plays an important role in anticancer treatment because it combines cell death with appearance of damage associated molecular patterns that have the potential to activate anticancer immunity. Effects of damage associated molecular patterns induced by aminolevulinic acid-based photodynamic therapy were studied mainly on dendritic cells. They have not been deeply studied on macrophages that constitute the essential component of the tumor microenvironment. The aim of this study was to analyze features of esophageal cancer cell death in relation to release capacity of damage associated molecular pattern species, and to test the effect of related extracellular environmental alterations on macrophages. Material and methods Esophageal Kyse 450 carcinoma cells were subjected to aminolevulinic acid-based photodynamic therapy at different concentrations of aminolevulinic acid. Resting, IFN/LPS and IL-4 macrophage subtypes were prepared from monocytic THP-1 cell line. Cell death features and macrophage modifications were analyzed by fluorescence-based live cell imaging. ATP and HMGB1 levels in cell culture media were determined by ELISA assays. The presence of lipid peroxidation products in culture media was assessed by spectrophotometric detection of thiobarbituric acid reactive substances. Results Aminolevulinic acid-based photodynamic therapy induced various death pathways in Kyse 450 cells that included features of apoptosis, necrosis and ferroptosis. ATP amounts in extracellular environment of treated Kyse 450 cells increased with increasing aminolevulinic acid concentration. Levels of HMGB1, detectable by ELISA assay in culture media, were decreased after the treatment. Aminolevulinic acid-based photodynamic therapy induced lipid peroxidation of cellular structures and increased levels of extracellular lipid peroxidation products. Incubation of resting and IL-4 macrophages in conditioned medium from Kyse 450 cells treated by aminolevulinic acid-based photodynamic therapy induced morphological changes in macrophages, however, comparable alterations were induced also by conditioned medium from untreated cancer cells. Conclusion Aminolevulinic acid-based photodynamic therapy leads to alterations in local extracellular levels of damage associated molecular patterns, however, comprehensive studies are needed to find whether they can be responsible for macrophage phenotype modifications.

Parvalbumin Interneuron Disorders Triggered by Oxidative Stress as a Common Mechanism Causing Schizophrenia in the Elderly: a Literature Review Study

Schizophrenia is a functional psychotic disorder with the main disturbance of the thought process and the disintegration of the thought process, affect or emotion, volition and psychomotor accompanied by a distortion of reality, especially due to delusions and hallucinations, fragmented associations resulting in incoherence, inadequate affect and emotion, and psychomotor which shows withdrawal, ambivalence and bizzare behavior. The research design used is the literature review method. Literature study is research carried out by researchers by collecting a number of articles or journals related to research problems and objectives. The study results show that various literature shows evidence that schizophrenia in the elderly occurs due to changes in antioxidant enzymes in schizophrenia. Increased levels of lipid peroxidation products and nitric oxide (NO) occurred in schizophrenia, while superoxide dismutase activity was found to decrease significantly in this disorder, but glutathione peroxidase and catalase activity had no effect in schizophrenia patients. In schizophrenic patients, it was found that there was an increase in the production of free radicals, therefore the administration of anti-oxidants is necessary to increase antioxidants which can reduce symptoms in schizophrenic patients.

An Overview on Naturally Occurring Phytoconstituent: Lithospermic Acid

Abstract: Lithospermic acid is a phenylpropanoid oligomer isolated from an aqueous extract of dried roots of various Lamiaceae and Boraginaceae plants and used as a folk medicine to treat cardiovascular disease and to improve body functions. The manuscript has been written to provide valuable insights into naturally occurring phytocomponent, Lithospermic acid, and even explore its therapeutic potential. The data have been gathered from books and web sources, including Science Direct, Publons, Web of Science, and Scopus of the latest year. Lithospermic acid is a conjugate of rosmarinic and caffeic acid with a dihydro benzofuran nucleus and possesses a high antioxidant potential and prevents the production of superoxide radicals and lipid peroxidation and protects the tissue from deleterious effects of reactive oxygen species. In addition, it also possesses a wide range of pharmacological activities, including reducing atherosclerosis, anti-inflammatory, hepatoprotective, anti-viral, HIV-1 integrase, and hyaluronidase inhibition, aldose reductase inhibition and improvement in uremic symptoms guanidino succinic acid level. Due to its anti-HIV activity, LA has gained much attention among the scientific community. Moreover, it is widely distributed to all the peripheral tissue in rats, and its metabolites undergo enterohepatic circulation and are excreted through biliary excretion. In this review, we concluded LA with its phytochemistry, pharmacokinetics, and pharmacological activities.

Piceatannol protects against myocardial ischemia/reperfusion injury by inhibiting ferroptosis via Nrf-2 signaling-mediated iron metabolism

Myocardial tissue ischemia damages myocardial cells. Although reperfusion is an effective technique to rescue myocardial cell damage, it may also exacerbate myocardial cell damage. Ferroptosis, an iron-dependent cell death, occurs following myocardial ischemia-reperfusion (I/R). Piceatannol (PCT) is a natural stilbene compound with excellent antioxidant properties that protect against I/R injury and exerts protective effects against ferroptosis-induced cardiomyocytes following I/R injury; however, the exact mechanism remains to be elucidated. PurposeThis study aims to investigate the protective effect and mechanism of PCT on myocardial ischemia-reperfusion injury. MethodsAn ischemia-reperfusion model was established via ligation of the left anterior descending branch of mice's hearts and hypoxia-reoxygenation (H/R) of cardiomyocytes. ResultsDuring ischemia-reperfusion, Nuclear factor E2-related factor 2 (Nrf-2) expression was downregulated, the left ventricular function was impaired, intracellular iron and lipid peroxidation product levels were elevated, and cardiomyocytes underwent ferroptosis. Furthermore, ferroptosis was enhanced following treatment with an Nrf-2 inhibitor. After PCT treatment, Nrf-2 expression significantly increased, intracellular ferrous ions and lipid peroxidation products significantly reduced, Ferroportin1 (FPN1) expression increased, and transferrin receptor-1 (TfR-1) expression was inhibited. ConclusionsPCT regulates iron metabolism through Nrf-2 to protect against myocardial cell ferroptosis induced by myocardial I/R injury.

Composition of fatty acids in a high-fat diet affects adipose tissue inflammation by inducing calreticulin on adipocytes and activating group 1 innate lymphoid cells.

Obesity-induced adipose tissue inflammation plays a critical role in the development of metabolic diseases. For example, NK1.1+ group 1 innate lymphoid cells (G1-ILCs) in adipose tissues are activated in the early stages of inflammation in response to a high-fat diet (HFD). In this study, we examined whether the composition of fatty acids affected adipose inflammatory responses induced by an HFD. Mice were fed a stearic acid (C18:0)-rich HFD (HFD-S) or a linoleic acid (C18:2)-rich HFD (HFD-L). HFD-L-fed mice showed significant obesity compared with HFD-S-fed mice. Visceral and subcutaneous fat pads were enlarged and contained more NK1.1+KLRG1+ cells, indicating that G1-ILCs were activated in HFD-L-fed mice. We examined early changes in adipose tissues during the first week of HFD intake, and found that mice fed HFD-L showed increased levels of NK1.1+CD11b+KLRG1+ cells in adipose tissues. In adipose tissue culture, addition of 4-hydroxynonenal, the most frequent product of lipid peroxidation derived from unsaturated fatty acids, induced NK1.1+CD11b+CD27- cells. We found that calreticulin, a ligand for the NK activating receptor, was induced on the surface of adipocytes after exposure to 4-hydroxynonenal or a 1-week feeding with HFD-L. Thus, excess fatty acid intake and the activation of G1-ILCs initiate and/or modify adipose inflammation.

From antioxidant defense system damage to programmed cell apoptosis: Understanding lethal mechanisms of cypermethrin on fish kidneys

Harmful effects of pesticide pollution on aquaculture have become increasingly urgent. The kidney, critical organ of the endocrine system in fish, is susceptible to some pollutants in the aquatic system. This study aimed to investigate the comprehensive effects and toxicological mechanisms of cypermethrin (CMN) on fish kidneys. The findings derived from the in vivo experiments demonstrated that exposure to CMN resulted in notable damage to the kidneys of grass carp, accompanied by impairment to the antioxidant defense system of kidney tissue, inducing severe oxidative stress. The activities of T-SOD, CAT, and GSH decreased, and lipid peroxidation product MDA content increased sharply. Subsequently, p-PERK, p-eIF2α, GRP78, and IRE1 significantly increased, suggesting a disturbance in the endoplasmic reticulum (ER) homeostasis. In addition, excessive oxidative stress and ER stress initiated programmed apoptosis. At cellular level in vitro, the changes of CMN did on damage degree of grass carp kidney cells were verified. Toxicity mechanism was consistent with the in vivo test. The information provided herein emphasized the assessment of pollution caused by the toxic organic insecticide CMN effects on the food chain of marine organisms. The results of this study revealed potential nephrotoxic mechanisms of CMN in fish and provide essential data for the safety monitoring and rational application of CMN. Together, these results shed light on protein homeostasis mechanisms that may help manage misfolded proteins under oxidative stress conditions.

Dietary Marine Oils Selectively Decrease Obesogenic Diet-Derived Carbonylation in Proteins Involved in ATP Homeostasis and Glutamate Metabolism in the Rat Cerebellum.

The regular intake of diets high in saturated fat and sugars increases oxidative stress and has been linked to cognitive decline and premature brain aging. The cerebellum is highly vulnerable to oxidative stress and thus, obesogenic diets might be particularly detrimental to this tissue. However, the precise molecular mechanisms behind obesity-related brain damage are still not clear. Since protein carbonylation, a biomarker of oxidative stress, influences protein functions and is involved in metabolic control, the current investigation addressed the effect of long-term high-fat and high-sucrose diet intake on the cerebellum of Sprague-Dawley rats by deciphering the changes caused in the carbonylated proteome. The antioxidant effects of fish oil supplementation on cerebellar carbonylated proteins were also investigated. Lipid peroxidation products and carbonylated proteins were identified and quantified using immunoassays and 2D-LC-MS/MS in the cerebellum. After 21 weeks of nutritional intervention, the obesogenic diet selectively increased carbonylation of the proteins that participate in ATP homeostasis and glutamate metabolism in the cerebellum. Moreover, the data demonstrated that fish oil supplementation restrained carbonylation of the main protein targets oxidatively damaged by the obesogenic diet, and additionally protected against carbonylation of several other proteins involved in amino acid biosynthesis and neurotransmission. Therefore, dietary interventions with fish oils could help the cerebellum to be more resilient to oxidative damage. The results could shed some light on the effect of high-fat and high-sucrose diets on redox homeostasis in the cerebellum and boost the development of antioxidant-based nutritional interventions to improve cerebellum health.

Foliar application of NaHS alleviates Cd toxicity in soybean plants through regulation of Glutathione metabolism

Hydrogen sulfide (H2S) regulates many critical processes of plants and their responses to abiotic stresses such as heavy metals. In the present study, the effect of sodium hydrogen sulfide (NaHS) as an H2S donor (0, and 50 μM) was investigated in soybean plants under Cd stress (0, and 50 μM). These experiments were done according to a factorial design based on a completely randomized design with three replications. Cd exposure reduced growth parameters and relative water content. Cd also caused a reduction in photosynthetic pigment, an increase in ion leakage and oxidative stress as indicated by lipid peroxidation and H2O2 production. These results demonstrated the toxicity of the applied Cd concentrations on soybean plants. However, foliar application of NaHS improved the shoot length and fresh weight on Cd-stressed plants. NaHS also alleviated the toxic effects of Cd on ion leakage, relative water content, and photosynthetic pigments of leaves. The activity of glutathione reductase and the expression of genes to the family of glutathione synthetase including glutathione synthetase, chloroplastic-like (LOC102663288) (GS288), glutathione synthetase, chloroplastic (LOC100778473) (GS473) and homoglutathione synthetase (Gene ID: 547,989) (HGS), were observed to be upregulated under the influence of NaHS treatment. However, the expression of glutathione synthetase, and chloroplastic-like glutathione synthetase (LOC100813419) (GS419)) were reduced by NaHS in Cd-stressed plants. These results confirm the regulatory effect of NaHS application on physiological parameters and glutathione metabolism at molecular levels on soybean plants.

The oxidized phospholipid PGPC impairs endothelial function by promoting endothelial cell ferroptosis via FABP3

Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2•−), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2•−, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.

Oral administration of resveratrol reduces oxidative stress generated in the hippocampus of Wistar rats in response to consumption of ethanol.

Chronic ethanol intake has been found to favor hippocampal deterioration and alter neuronal morphological maturation; resveratrol has been suggested as an antioxidant that may counteract these effects. The objective of this study was to analyze the effect of resveratrol on oxidative stress markers, endogenous antioxidant system in the hippocampus, and the behavior of male Wistar rats administered different concentrations of ethanol. The animals, at 3 months old, were randomly distributed into 11 study groups (n = 6/group), orally administered (5 days on, 2 days off) with water (control), ethanol (10, 20, 30, 40 or 50%), or ethanol (10, 20, 30, 40 or 50%) plus resveratrol (10 mg/Kg/day) for 2 months. Subsequently, the production of nitrites, malondialdehyde, and 4-hydroxy-alkenal (HNE) and the enzymatic activity of catalase and superoxide dismutase (SOD) were quantified. The levels of nitric oxide and lipid peroxidation products were significantly increased in each ethanol concentration and were statistically different compared to the control group; however, resveratrol significantly reduced oxidative stress caused by high ethanol concentration. The SOD and CAT did not present significant changes with respect to the controls in any of the study groups. In the different concentrations of ethanol used, GR increases significantly in the groups administered with resveratrol but not GPx. Resveratrol was shown to maintain the results similar to the control at most ethanol concentrations. Our results suggest that resveratrol prevents oxidative stress induced by ethanol in the hippocampus by decreasing cellular lipid peroxidation, but does not prevent the activation of catalase or SOD enzymes; however, allows glutathione to be kept active and in adequate concentrations in its reduced form and avoids alterations in the locomotor system.

The protective effect of PL 1-3 on D-galactose-induced aging mice.

The aging population has become an issue that cannot be ignored, and research on aging is receiving increasing attention. PL 1-3 possesses diverse pharmacological properties including anti-oxidative stress, inhibits inflammatory responses and anti-apoptosis. This study showed that PL 1-3 could protect mice, especially the brain, against the aging caused by D-galactose (D-gal). D-gal could cause oxidative stress, inflammation, apoptosis and tissue pathological injury and so on in aging mice. The treatment of PL 1-3 could increase the anti-oxidative stress ability in the serum, liver, kidney and brain of aging mice, via increasing the total antioxidant capacity and the levels of anti-oxidative defense enzymes (superoxide dismutase, glutathione peroxidase, and catalase), and reducing the end product of lipid peroxidation (malondialdehyde). In the brain, in addition to the enhanced anti-oxidative stress via upregulating the level of the nuclear factor erythroid 2-related factor 2 and heme oxygenase 1, PL 1-3 could improve the dysfunction of the cholinergic system via reducing the active of acetylcholinesterase so as to increase the level of acetylcholine, increase the anti-inflammatory and anti-apoptosis activities via downregulating the expressions of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α) and pro-apoptosis proteins (Bcl-2 associated X protein and Caspase-3) in the D-gal-induced aging mice, to enhance the anti-aging ability via upregulating the expression of sirtuin 1 and downregulating the expressions of p53, p21, and p16. Besides, PL 1-3 could reverse the liver, kidney and spleen damages induced by D-gal in aging mice. These results suggested that PL 1-3 may be developed as an anti-aging drug for the prevention and intervention of age-related diseases.

Quercetin alleviates PM2.5-induced chronic lung injury in mice by targeting ferroptosis.

PM2.5 is a well-known harmful air pollutant that can lead to acute exacerbation and aggravation of respiratory diseases. Although ferroptosis is involves in the pathological process of pulmonary disease, the potential mechanism of ferroptosis in PM2.5-caused lung inflammation and fibrosis need to be further clarified. Quercetin is a phenolic compound that can inhibit ferroptosis in various diseases. Hence, this study explores the role of ferroptosis in lung injury induced by PM2.5 in order to further elucidate the beneficial effect of quercetin and its underlying mechanism. C57BL/6J mice were treated with either saline or PM2.5 by intratracheal instillation 20 times (once every two days). Additionally, PM2.5-treated mice were supplemented with two doses of quercetin. Lung injury, lipid peroxidation, iron content and ferroptosis marker protein expression and the Nrf2 signaling pathway were evaluated. In vitro, cell experiments were applied to verify the mechanisms underlying the links between Nrf2 signaling pathway activation and ferroptosis as well as between ferroptosis and inflammation. In vivo, PM2.5 increased lung inflammation and caused lung fibrosis and increased lipid peroxidation contents, iron contents and ferroptosis markers in lung tissues; these effects were significantly reversed by quercetin. Additionally, quercetin upregulated the nuclear Nrf2 expression and downregulated Keap1 expression in lung tissues of PM2.5-exposed mice. Quercetin decreased lipid peroxidation products, iron contents and ferroptosis levels and increased the nuclear translocation of Nrf2 and the degradation of Keap1 in PM2.5-exposed BEAS-2B cells. Moreover, we found that quercetin and dimethyl fumarate markedly decreased lipid peroxidation production and ferroptosis by activating the Nrf2-Keap1 pathway in PM2.5-exposed cells. Furthermore, quercetin reduced inflammatory cytokines and TGF-β1 in PM2.5-exposed cells. Our data suggested that Nrf2 is involved in ferroptosis in PM2.5-induced lung injury, and quercetin can alleviate these adverse effects via activating Nrf2-Keap1 signaling pathway.

Targeting ferroptosis withnatural products inliver injury: new insights frommolecular mechanisms totargeted therapies.

Ferroptosis is a brand-new type of controlled cell death that is distinguished by its reliance on iron and the production of lipid peroxidation. The role of ferroptosis in damaging liver disorders has attracted a lot of attention in recent years. One effective strategy to reduce liver damage is to target ferroptosis. The purpose of this review is to clarify the connection between ferroptosis and liver damage and to look into the potential contribution of natural products to the clinical management of liver damage and the discovery of novel medications. To study the methods by which natural products operate on ferroptosis to cure liver damage and their main signaling pathways, we searched databases from the time of initial publication to August 2023 in PubMed, EMBASE, Web of Science, Ovid, ScienceDirect, and China National Knowledge Infrastructure. The liver illness that each natural product treats is categorized and summarized. It's interesting to note that several natural compounds, such Artemether, Fucoidan sulfate, Curcumin, etc., have the benefit of having many targets and multiple pathways of action. We saw that in human samples or animal models of liver injury, ferroptosis indicators were activated, lipid peroxidation levels were elevated, and iron inhibitors had the ability to reduce liver damage. Liver damage can be treated with natural products by regulating ferroptosis. This is mostly accomplished through the modulation of Nrf2-related pathways (e.g., Conclusions and Astaxanthin), biological enzymes like GPX4 and the SIRT family (e.g., Chrysophanol and Decursin), and transcription factors like P53 (e.g., Artemether and Zeaxanthin). This review proposes a promising path for the therapeutic therapy of liver damage by providing a theoretical foundation for the management of ferroptosis utilizing natural ingredients.

A Prooxidant and an Antioxidant Sow’s Status with Hepathopathy

The role of lipid peroxidation in the pathogenesis of liver diseases in sows was studied. The state of the antioxidant system in these diseases was also assessed. The liver of sows has been examined after slaughter. There were four groups formed: healthy, acute and chronic hepatosis (HS), and liver cirrhosis. An increase in the level of endogenous intoxication has established, the content of primary (diene conjugates), secondary (malondialdehyde, ketodienes, ketotrienes), and final (Schiff base) products of lipid peroxidation in the blood of sows with hepatopathy. Also noticed that sows with hepatopathy had decreased antioxidant protection, catalase activity, and concentration of tocopherol and ascorbic acid. The level of change was growing with a gravity of hepatopathy. The most expressed disturbance has been observed in sows with liver cirrhosis.

Effect of melatonin and hydropriming on germination of aged triticale and rye seeds

The formation of reactive oxygen species, which initiate lipid peroxidation of membranes and disruption of all membrane-associated processes, is one of the critical factors causing seed senescence and loss of germinability. Melatonin is currently considered one of the powerful antioxidant bioregulators that influence many plant functions, including their resistance to stress factors and seed germination. However, the effect of melatonin on the germination of old triticale and rye seeds has not been specifically investigated. The work aimed to study the effect of melatonin treatment and the well-known procedure of hydropriming (soaking in water with subsequent drying of seeds) on the germination of seeds of triticale ‘Raritet’ and rye ‘Pamyat Khudoerka’ with low germination capacity and the state of antioxidant system in seedlings. Hydropriming had a small but significant effect on the germination of triticale seeds at p ≤ 0.05 and significantly increased the germination of rye seeds. Melatonin treatment positively impacted both crop seed germination and significantly exceeded the effects of hydropriming. The most significant effect was observed when melatonin was used at a concentration of 20 μM. The accumulation of shoot and root biomass also increased under hydropriming and (to a greater extent) melatonin. Melatonin treatment led to a significant decrease in the generation of superoxide anion radical and the content of hydrogen peroxide and malonic dialdehyde, a product of lipid peroxidation, in seedlings of both crops. Additionally, melatonin increased the activity of superoxide dismutase and catalase in both crops. The anthocyanin content increased in the seedlings of both cereals under the influence of melatonin. The effect of hydropriming on indicators characterising the prooxidant and antioxidant balance was insignificant. A conclusion was drawn on the ability of exogenous melatonin to enhance the germination of old triticale and rye seeds and the connection of this effect with the regulation of the antioxidant system.

Pinobanksin ameliorated DSS-induced acute colitis mainly through modulation of SLC7A11/glutathione-mediated intestinal epithelial ferroptosis.

Inhibition of ferroptosis in intestinal epithelial cells serves as an attractive target for the development of therapeutic strategies for colitis. Pinobanksin, one of the main flavonoids derived from propolis, possesses significant anti-inflammatory effects and inhibits the cell death of several cell lines. Here, we evaluated whether pinobanksin influenced colitis by modulation of epithelial ferroptosis. Mice treated with 2.5% DSS dissolved in sterile distilled water were established for an acute colitis model. The mitochondrial morphology, colonic iron level, lipid peroxidation products MDA/4-HNE, and lipid reactive oxygen species levels were measured to assess ferroptosis in epithelial cells. RNA-seq and functional analyses were performed to reveal key genes mediating pinobanksin-exerted modulation of ferroptosis. We found that pinobanksin, at different doses, induced significant anti-colitis effects and inhibited the elevated ferroptosis in colonic epithelial cells isolated from DSS-treated mice largely by activating GPX4 (negative regulator of ferroptosis). Furthermore, RNA-seq assays indicated that pinobanksin significantly increased the cystine transporter SLC7A11 in colonic tissues from mice with colitis. Depletion of SLC7A11 largely blocked pinobanksin-induced promotion of cystine uptake/glutathione biosynthesis and suppression of ferroptosis in epithelial cells from mice with colitis or IEC-6 cells pretreated with RSL3. Altogether, pinobanksin alleviated DSS-induced colitis largely by inhibition of ferroptosis in epithelial cells. Activation of SLC7A11 by pinobanksin resulted in the promotion of cystine uptake and enhancement of glutathione biosynthesis. This work will provide novel guidance for the clinical use of pinobanksin to treat colitis through inhibition of epithelial ferroptosis.

Consumption of foods contaminated with heavy metals and their association with cardiovascular disease (CVD) using GAM software (cohort study)

IntroductionHeavy metals can enter the environment and food through industrial activities, acid rain, chemical fertilizers, pesticides, and sewage. A large amount of these metals is dangerous because they tend to bio accumulate. A concern with these metals is the long-term, low-dose exposure seen in the general population. HMs can cause disorders in the cardiovascular system through various mechanisms such as the production of free radicals, DNA damage, lipid peroxidation, and oxidative stress. Material and methodFood items measured in the present study included rice, bread, and vegetables. 210 participants (105 controls and 105 patients) were randomly selected for this study. The demographic information of the subjects was obtained from the Hoveyzeh Cohort Center. The relationship between heavy metals in food and cardiovascular diseases is investigated by The Generalized Additive Model (GAM). ResultThe results of the present study showed that when urine Cd was smoothed based on rice Cd, there was a significant correlation between urine Cd and Cd consumed in vegetables and rice. The GAM coefficient for urinary Cd excreted in case-control groups and Cd consumed in vegetables were 479.79(SE: 6.49–73.87) and 818.56(SE: 11.96–68.43), respectively, and for rice consumed, it was 0.03(SE: 0.015–2.103) and 0.04(SE: 0.017–2.338), respectively. The GAM coefficient for As consumption in vegetables and As in urine of case and control groups was 1.61 (SE: 9.48–0.16) and 22.36 (SE: 13.60–1.64), respectively. The same coefficient for rice consumption in case and control groups was 4.5 (SE: 0.62–7.22) and 10.48 (SE: 1.46–7.16), respectively. There was a very strong and significant correlation between the Sr in the urine of both groups and the Sr in the food consumed, so that the urinary Sr in the control group is excreted more than in the cardiovascular group. ConclusionGAM analysis indicates that As in vegetable and rice is more than the standard limitation value. Also, Sr and Cd in vegetables, rice, and bread were more than the standard limitation value. According to the GAM model As had a significant value in rice and vegetables indicating that As is more than the standard limitation value, therefore, it is associated with CVD.

Unlocking the potential of deferoxamine: a systematic review on its efficacy and safety in alleviating myocardial ischemia-reperfusion injury in adult patients following cardiopulmonary bypass compared to standard care.

Reperfusion injury, characterized by oxidative stress and inflammation, poses a significant challenge in cardiac surgery with cardiopulmonary bypass (CPB). Deferoxamine, an iron-chelating compound, has shown promise in mitigating reperfusion injury by inhibiting iron-dependent lipid peroxidation and reactive oxygen species (ROS) production. The objective of our study was to analyze and evaluate both the efficacy and safety of a new and promising intervention, that is, deferoxamine for ischemia-reperfusion injury (I/R). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines are used to perform the study. We conducted a systematic review following PRISMA guidelines to assess the efficacy and safety of deferoxamine in reducing I/R injury following CPB. A comprehensive search of electronic databases, namely, PubMed, Scopus, and Embase, yielded relevant studies published until August 18, 2023. Included studies evaluated ROS production, lipid peroxidation, cardiac performance, and morbidity outcomes. (a) ROS production: Multiple studies demonstrated a statistically significant decrease in ROS production in patients treated with deferoxamine, highlighting its potential to reduce oxidative stress. (b) Lipid peroxidation: Deferoxamine was associated with decreased lipid peroxidation levels, indicating its ability to protect cardiac tissue from oxidative damage during CPB. (c) Cardiac performance: Some studies reported improvements in left ventricular ejection fraction and wall motion score index with deferoxamine. Our review shows that deferoxamine is an efficacious and safe drug that can be used to prevent myocardial I/R injury following CPB. It also highlights the need for trials on a larger scale to develop potential strategies and guidelines on the use of deferoxamine for I/R injury.

Krill Oil Ameliorates Liver Injury in Diabetic Mice by Activating Antioxidant Capacity and Inhibiting Ferroptosis.

Diabetic liver injury (DLI) has raised attention in recent years. Liver injury results from type 2 diabetes mellitus (T2DM), and in turn accelerates T2DM development by exacerbating insulin resistance. However, effective approaches for mitigating DLI are surprisingly rare. Krill oil (KO) is an alternative source of omega-3 polyunsaturated fatty acids, possessing antioxidant and anti-inflammatory capacities. Here we investigated the effect of KO supplementation on DLI in a mouse model of T2DM induced by streptozotocin and high-fat diet. The diabetic mice developed glucose intolerance, elevated serum alanine aminotransferase and aspartate aminotransferase, and hepatic pathological injuries such as vacuolation, lipid accumulation and fibrosis deposition, the effects of which were mitigated by KO. Further investigation showed that KO ameliorated the DM-induced expression of fibrotic and inflammatory genes. Notably, KO dramatically reduced hepatic oxidative gene expression, lipid peroxidation and ROS production, all of which are hallmarks of ferroptosis. The inhibitory effect of KO on ferroptosis was confirmed by the KO-decreased hepatic expression of GPX4, COX2 and ACSL4, as well as the KO-reduced hepatic iron deposition. Further, KO restored hepatic NRF2 antioxidant signaling which combats ferroptosis. The present study may provide KO supplementation as a viable approach for the intervention of DLI.