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Alzheimer' s disease (AD) is a progressive neurodegenerative disorder histologically characterized by the presence of senile plaques and neurofibrillary tangles (NFTs) found in and around pyramidal neurons in cortical tissue. Mounting evidence suggests regional increased iron load and dyshomeostasis have been associated with oxidative stress, oxidation of proteins and lipids, and cell death, and appears to be a risk factor for more rapid cognitive decline, thereby involved in multiple aspects of the pathophysiology of AD. Ferroptosis is a newly identified iron-dependent lipid peroxidation-driven cell death and emerging evidences have demonstrated the involvement of ferroptosis in the pathological process of AD. Notably, some novel compounds targeting ferroptosis can relieve AD-related pathological symptoms in AD cells and animal model and exhibit potential clinical benefits in AD patients. This review systematically summarizes the growing molecular and clinical evidence implicating ferroptosis in the pathogenesis of AD, and then reviews the application of ferroptosis inhibitors in mouse/cell models to provide valuable information for future treatment and prevention of AD.
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OBJECTIVE@#To assess acute toxicity, the in vitro and in vivo effects of methanol and ethyl acetate extracts (JME and JEE) of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver enzymes.@*METHODS@#Acute toxicity of JME and JEE was determined using Lorke's method. In vitro and in vivo opening of the mitochondrial membrane permeability transition pore (MMPT pore) was spectrophotometrically assayed. Production of malondialdehyde (MDA) as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase (ALP), aspartate and alanine aminotransferase (AST and ALT) and gamma-glutamyl transferase (GGT) was also investigated.@*RESULTS@#JME had an LD50 of 3 808 mg/kg b.w whereas JEE had an LD50 greater than 5 000 mg/kg b.w. of rats. After the rats have been fed with both extracts, a photomicrograph of a piece of liver tissue showed no apparent symptoms of toxicity. From the in vitro and in vivo studies, both extracts prompted intact mitochondria to open their MMPT pores. When compared to the control, lipid peroxide product release and ATPase activity were significantly increased (P < 0.05) in vitro and in vivo. The activities of AST, ALT, and GGT were all reduced at 50 mg/kg when treated with JME, but the activity of AST was considerably enhanced when treated with JEE (P < 0.05). The results revealed that both JME and JEE of the Jatonik polyherbal mixture had low toxicity, profound MMPTpore induction, and enhanced ATPase activity, but an increased MDA production.@*CONCLUSION@#Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis, however, further studies are needed to better clarify the molecular mechanism involved in these phenomena.
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Objective: To determine the impact of COVID-19 on vitamin E concentrations and oxidative stress in patients affected by the disease. Method: We conducted a systematic review using observational studies published between 2020 and 2023, which addressed the impact of COVID-19 on vitamin E concentrations and oxidative stress in patients affected by the disease. Review articles, clinical trials, letters to the editor, as well as studies conducted with pregnant women, animals and/or in vitro tests, and in languages other than English were excluded from this search. Studies were selected through a literature search in the following electronic databases: PubMed, Science Direct, and Web of Science, from October 2022 to May 2023. Results: Three articles were included in this review, consisting of patients with mild to severe symptoms, including those hospitalized in the intensive care unit. The reduction in vitamin E concentrations was in all studies accompanied by a reduction in enzymes involved in antioxidant action, such as superoxide dismutase, glutathione peroxidase, and glutathione reductase. In parallel to this, studies showed elevated concentrations of lipid peroxidation markers, such as malondialdehyde and myeloperoxidase. Conclusion: Infection with the SARS-COV-2 alters the activity of antioxidant cells and free radical defense agents.
Objetivo: Determinar el impacto del COVID-19 sobre las concentraciones de vitamina E y el estrés oxidativo en pacientes afectados por la enfermedad. Método: Se trata de una Revisión Sistemática, realizada mediante una prospección de estudios observatorios publicados entre 2020 y 2023, que abordaron el impacto de la COVID-19 sobre las concentraciones de vitamina E y el estrés oxidativo en pacientes afectados por la enfermedad. Se excluyeron de esta búsqueda artículos de revisión, ensayos clínicos, cartas al editor, así como estudios realizados con mujeres embarazadas, animales y/o ensayos in vitro, y en idiomas distintos al inglés. Los estudios se seleccionaron mediante una búsqueda bibliográfica en las siguientes bases de datos electrónicas: PubMed, Science Direct y Web of Science, desde octubre de 2022 hasta mayo de 2023. Resultados: Se incluyeron tres artículos en esta revisión, que consistían en pacientes con síntomas de leves a graves, incluidos los hospitalizados en la unidad de terapia intensiva. La reducción de las concentraciones de vitamina E se acompañó en todos los estudios de una reducción de las enzimas implicadas en la acción antioxidante, como la superóxido dismutasa, la glutatión peroxidasa y la glutatión reductasa. Paralelamente, los estudios mostraron concentraciones elevadas de marcadores de peroxidación lipídica, como el malondialdehído y la mieloperoxidasa. Conclusiones: La infección por el virus del SARS-CoV-2 altera la actividad de las células antioxidantes y de los agentes de defensa contra los radicales libres.
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Obesity is mainly caused by consumption of high fat diet (HFD) and a lack of physical activity. Physical activity is an efficient strategy to delay development of obesity. In this studyv we tried to evaluate attenuating properties of 16 weeks endurance training on plasma oxidative stress and some biochemical parameters in HFD induced obese rats. Twenty-four male Wistar rats were randomly divided into four groups: standard diet group (SD), standard diet with endurance training group (ESD), HFD group and HFD with endurance training group (EHFD). After sixteen weeks, plasma was prepared and evaluated for measurement of different parameters. The results showed that HFD significantly decreased the activities of superoxide dismutase (33.58%), catalase (26.51%) and glutathione S-transferase (22.77%), while endurance training increased these enzymes activities. However, exercise ameliorated the increased malondialdehyde level and depletion of glutathione. In addition, it significantly reduced the increased levels of liver enzymes activities and lipid profiles. These findings suggest that endurance training has found to have beneficial effects against HFD-induced oxidative damage through increasing reduced antioxidants levels and inhibition of lipid peroxidation due to its antioxidant property. Thus, it can be considered an interesting strategy for the management of obesity related diseases.
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Objetivo: Establecer la relación entre los niveles de estrés laboral y la producción de malondialdehído (MDA), como producto de la peroxidación lipídica, en los trabajadores de la Universidad Católica Santo Toribio de Mogrovejo en Chiclayo. Materiales y métodos: Investigación descriptiva, de tipo correlacional. La muestra estuvo conformada por 72 trabajadores, de los cuales 37 eran docentes y 35, administrativos. Se midió espectrofotométricamente el MDA presente en el plasma mediante la reacción con ácido tiobarbitúrico (TBA). Para determinar el estrés se utilizó la Escala de Estrés Laboral, elaborada por Ivancevich y Matteson en 1989, y adaptada por Suárez en 2013. El instrumento consta de 25 ítems y está compuesto por siete dimensiones: clima organizacional, estructura organizacional, territorio organizacional, tecnología, influencia del líder, falta de cohesión y respaldo del grupo. Resultados: En la investigación participaron 23 hombres y 49 mujeres. La edad media fue de 45,1 años y la desviación estándar de 11,33, con un mínimo de 25 y máximo de 68 años. El estrés laboral elevado se observó en mayor porcentaje en las dimensiones influencia del líder (19,40 %), estructura organizacional (16,70 %) y territorio organizacional (16,70 %). El 54 % (39) de los trabajadores presentaron niveles altos del MDA, es decir, valores superiores en plasma a 3,94 µM. De ellos, 17 fueron hombres y 22, mujeres. Al evaluar, con Rho de Spearman al 95 % de significancia, la correlación entre los valores de MDA con el sexo, trabajar en otro centro laboral y la atención de hijos en el hogar, resultaron valores de p = 0,08, p = 0,61 y p = 0,33, respectivamente; por lo tanto, no hubo significancia estadística. Conclusiones: Del total de trabajadores evaluados, el 54 % presentó alta concentración de malondialdehído plasmático. Aunque no hubo correlación estadísticamente significativa, las dimensiones con alto nivel de estrés, según la prueba aplicada, influencia del líder, estructura organizacional y territorio organizacional mostraron niveles de estrés en el orden de 19,40 %, 16,70 % y 16,70 %, respectivamente.
Objective: To establish the relationship between occupational stress levels and the production of malondialdehyde (MDA), as a product of lipid peroxidation, among workers of Universidad Católica Santo Toribio de Mogrovejo in Chiclayo. Materials and methods: A descriptive, correlational research. The sample consisted of 72 workers, 37 of whom were professors and 35 administrative staff members. Plasma MDA was measured spectrophotometrically by thiobarbituric acid (TBA) reaction. To determine stress, the Occupational Stress Scale, developed by Ivancevich and Matteson in 1989 and adapted by Suárez in 2013, was used. The instrument had 25 items and seven dimensions: organizational climate, organizational structure, organizational territory, technology, leadership influence, lack of cohesion and group support. Results: Twenty-three men and 49 women participated in the research. The mean age was 45.1 years and the standard deviation was 11.33, with a minimum of 25 and a maximum of 68 years. The highest percentage of high occupational stress was observed in the dimensions leadership influence (19.40 %), organizational structure (16.70 %) and organizational territory (16.70 %). A total of 39 workers (54 %), 17 of whom were men and 22 were women, had high levels of MDA-i.e., plasma values higher than 3.94 µM. Spearman's Rho at 95 % confidence interval showed that the correlation between MDA values and sex, working in another workplace and childcare at home were p = 0.08, p = 0.61 and p = 0.33, respectively; therefore, there was no statistical significance. Conclusions: Out of all workers, 54 % had high plasma levels of MDA. Although no statistically significant correlation was found, the dimensions leadership influence, organizational structure and organizational territory showed high stress levels on the order of 19.40 %, 16.70 % and 16.70 %, respectively.
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Benzene is a notorious toxicant that is responsible for a host of diseases including leukemia. Its concentration in the environment is increasing day-by-day due to excessive automobile use, accelerated industrial activities and cigarette smoke. The awareness on the harmful effects of benzene on health is limited and no antidote has been reported yet. In this study, an attempt has been made to find out a suitable remedy to overcome benzene toxicity in a living organism from a natural source with the seeds of the plant Moringa oleifera (MO). Thirty six Wistar rats were considered for the study and divided into six groups (n=6). While group I remained as control with normal animals, those in groups II – VI received benzene by oral route (800 mg/kg body weight) for 28 consecutive days. On day 29, the benzene-treated animals in groups III – VI received respectively the standard drug ascorbic acid (AA, 25 mg/kg body weight) and MO (50, 100 and 200 mg/kg body weight) for the following 7 days. Group II rats that received only benzene served as negative control without any treatment. On day 36, all the animals were sacrificed and vital organs liver and kidney were removed for studying lipid peroxidation (LPO) and antioxidant markers [Superoxide dismutase (SOD), Total reduced glutathione (TRG), Glutathione peroxidase (GPx) and Catalase (CAT)] in addition to histopathological changes in the tissues. The results of the study revealed that significant changes occurred in the above parameters due to benzene dosing to animals were reverted to near normal values on MO administration in the liver and kidney tissues as compared to untreated animals, suggesting MO’s pro-active role in attenuating benzene toxicity.
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Autophagy is a conservative biological process of maintaining internal balances through degrading damaged proteins, organelles and intracellular pathogens.It may promote cell survival and accelerate cell death.Ferroptosis is a newly discovered regulated form of cell death characterized by lipid peroxidation and membrane damage in 2012.In recent years, more and more studies have demonstrated complex interactions between autophagy and ferroptosis.Various forms of cell death are regulated during the progression of kidney diseases.And autophagy and ferroptosis play important roles.However, potential connections between autophagy and ferroptosis in renal injury disease has not been fully elucidated.This review focused upon on the regulatory role of autophagy in ferroptosis and its possible link to renal injury, providing new theoretical rationales for researches on acute or chronic kidney injury.
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Liver ischemia reperfusion injury (IRI) is one of the main causes of liver dysfunction or functional failure after liver transplantation or liver resection. As the main organ of lipid metabolism, liver is closely related to lipid metabolic balance. Lipoxygenase is a non-heme iron-containing oxidases that oxidizes polyunsaturated fatty acids to produce hydroxy-eicosanotetraenoic acid. Lipoxygenase is excessively expressed during liver ischemia, causing lipid metabolic disorders. High expression of several proinflammatory cytokines induced by lipoxygenase during liver reperfusion. Lipid peroxidation induced by lipoxygenase leads to the production of lipid oxygen free radicals, which induces iron death mainly characterized by lipid peroxidation, thus affecting apoptosis and tissue damage. This review mainly introduces the latest progress of lipoxygenase in liver IRI.
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Ferroptosis is an iron-dependent, apoptotic cell death caused by massive lipid peroxidation-mediated cell membrane damage. Recent evidence suggests that exosomes, as a 30-100 nm diameter follicular body, contain a variety of active ingredients such as proteins, various RNAs and lipids that can have a great impact on the diagnosis and treatment of related diseases by regulating cellular iron death. To this end, this paper elaborates the research significance of exosomes in the regulation of cell ferroptosis, analyzes their role in disease treatment, and reviews the relevant reports and studies on exosomes regulating cell ferroptosis in recent years.
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Objective:To investigate the changes of glutathione peroxidase 4 (GPX4) in retinal photoreceptor cells, and the related mechanism correlated with retinal photoreceptor cell damage.Methods:The posterior segment tissues of 8 age-matched male donors were collected from the Body (Organ) Donation Register and Corneal Receiving Station of Tongji Hospital of Wuhan Red Cross from 2018 to 2021, including 4 non-diabetic donors and 4 diabetic donors.The tissues were divided into diabetes group and control group according to their donors.A total of 14 healthy SPF 8-week-old male C57BL/6 mice were selected and randomly divided into diabetes group and control group by the random number method, with 7 mice in each group.The mice in diabetes group were intraperitoneally injected with streptozotocin at a dose of 50 mg/kg for 5 days, and no intervention was given to mice in control group.Mouse photoreceptor cells 661W were divided into advanced glycation end products (AGEs) group and control group.AGEs group was treated with 100 μg/ml AGEs for 24 hours to simulate diabetic injury, and no intervention was given to control group.The outer segment morphology of retinal photoreceptors in human and mouse retinas was observed by hematoxylin-eosin staining.The expressions of glial fibrillary acidic protein (GFAP), rhodopsin and GPX4 in human and mouse retinas were detected by immunofluorescence staining.The expressions of GFAP, rhodopsin and GPX4 in mouse retina and the expression of GPX4 in 661W cells were determined by Western blot.The activity of 661W cells was detected by cell counting kit-8 (CCK8) method.The concentration of malondialdehyde (MDA) in mouse retina and cells was detected by TBA method.The activity of superoxide dismutase (SOD) in mouse retina and cells was detected by hydroxylamine assay.The use of human tissues was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology (No.TJ-C20230301). The animal experiments were conducted with reference to the Standards Guide for the Care and Use of Laboratory Animals of the National Institutes of Health, and the study protocol was approved by the Experimental Animal Ethics Committee of Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology (No.TJH-2016001).Results:Hematoxylin-eosin staining showed that retinal photoreceptor outer segments were deformed or broken in diabetic donors and diabetic mice compared with control groups.GFAP fluorescent signal mainly appeared in the inner retina of human and mice, and the stained cells were spindle or polygonal, which was consistent with the shape of glial cells.The retinal GFAP fluorescent signal of diabetic tissue and mouse groups was stronger than that of respective control groups.Rhodopsin was only expressed in the outer segment layer of photoreceptors with clear boundaries, and GPX4 was expressed in the whole retina with strong signal in the outer segment layer of photoreceptors.The fluorescent signals of rhodopsin and GPX4 in diabetic tissue and mouse groups were weaker than those in respective control groups.The relative expressions of GFAP were significantly higher and the relative expressions of rhodopsin and GPX4 were significantly lower in diabetic tissue and mouse groups than in respective control groups (all at P<0.05). The cell viability of AGEs group was significantly lower than that of control group ( t=13.490, P<0.001). The relative expression of GPX4 protein in AGEs group was 0.42±0.12, which was significantly lower than 1.00±0.04 in control group ( t=9.041, P<0.001). MDA concentration was higher and SOD activity was lower in retinal tissue of diabetic mice and AGEs group than those in respective control groups, and the differences were statistically significant (all at P<0.05). Conclusions:Diabetes can reduce the GPX4 level in retinal photoreceptor cells and cause the imbalance of oxidation-antioxidant system, which may be the mechanism of the damage to retinal photoreceptor cells caused by diabetes.
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Objective:To study the effects of tetramethylpyrazine on the expressions of ferroptosis related molecules after spinal cord injury; To explore the mechanism of tetramethylpyrazine promoting the repair of spinal cord injury (SCI).Methods:Totally 36 SD rats were divided into sham-operation group, model group and tetramethylpyrazine group according to random number table method, with 12 rats in each group. The rats in the sham-operation group underwent laminectomy without injury to the spinal cord. The SCI model was prepared in the other two groups. The rats in the tetramethylpyrazine group were intraperitoneally injected with tetramethylpyrazine of 80 mg/kg, and the rats in the sham-operation group and model group were intraperitoneally injected with the same volume of normal saline, once a day, continuous intervention for 28 days. One day before operation and 1, 3, 5, 7, 14, 21, 28 days after operation, BBB limb motor function score was used to evaluate the limb motor function of rats. Nissl staining was used to observe the morphology of neurons. Prussian staining was used to observe iron deposition. Assay kit was used to detect the contents of MDA and ROS in spinal cord tissue. Western blot was used to detect the protein expressions of xCT, GPX4 and ACSL4, and qPCR was used to detect the mRNA expressions of mRNA of xCT, GPX4 and ACSL4.Results:On the 14th, 21st and 28th days after operation, compared with the model group, the BBB score of tetramethylpyrazine group increased ( P<0.01); tetramethylpyrazine could significantly improve the morphology and structure of neurons and reduce the iron content in spinal cord tissue; compared with the model group, the contents of MDA and ROS in the spinal cord tissue of tetramethylpyrazine group decreased ( P<0.01); the levels of xCT and GPX4 mRNA and protein increased ( P<0.01), while the expression of ACSL4 mRNA and protein decreased ( P<0.01). Conclusion:Tetramethylpyrazine can regulate lipid peroxidation by regulating the expressions of ferroptosis related molecules, which is conducive to the recovery of limb motor function in rats with spinal cord injury.
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@#Ferroptosis is a novel iron-dependent mode of programmed cell death characterized by iron deposition and accumulation of lipid peroxidation. More and more studies have found that ferroptosis is closely related to the pathogenesis of type 2 diabetes mellitus （T2DM）. The yin-fire theory is an important part of LI Gao's spleen-stomach theory， and it is believed that qi-fire imblance and yin-fire internal generation is the main pathogenesis of T2DM. Abnormal iron metabolism may be an important prerequisite for T2DM yin-fire internal generation， while oxidative stress is the specific manifestation of T2DM qi-fire imbalance. Reactive oxygen species （ROS） is the end product of qi-fire imbalance， and lipid peroxide is the pathological products of T2DM yin-fire internal generation. This study intends to explore the pathological mechanism of qi-fire imbalance and yin-fire internal generation from the perspectives of iron metabolism， oxidative stress and lipid peroxidation， enriching the modern connotation of yin-fire theory， and benefiting traditional Chinese medicine to target against ferroptosis， and prevent and treat T2DM precisely.
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Ferroptosis is a new type of programmed cell death different from other cell death pathways such as apoptosis,autophagy,necrosis,and pyroptosis in terms of initiation,mechanisms,and molecular characteristics.As the accumulation of phospholipid hydroperoxides is the hallmark of ferroptosis,the balance between oxidative damage and antioxidant defense is critical to the regulatory mechanism of ferroptosis.In cancer,the upregulation of antioxidant defense pathways can inhibit ferroptosis,thereby promoting cancer cells to survive the oxidative stress and develop drug resistance.This review systematically introduces the main features and regulatory mechanisms of ferroptosis.In addition,we summarize the role of ferroptosis in the progression and drug resistance of malignant tumors,providing novel implications for further research on the pathogenesis of malignant tumors and discovery of new targets for anti-cancer therapy.
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Humans , Ferroptosis , Antioxidants , Apoptosis , Neoplasms , AutophagyABSTRACT
Ferroptosis is a unique mode of iron-dependent cell death driven by lipid peroxidation. It is characterized by morphological changes in mitochondria, including densification of mitochondrial membranes and associated reduction in the volume, rupture of outer membranes and reduction or disappearance of the mitochondrial crest, which is different from that of apoptosis, autophagy and pyroptosis. Mitochondria, as the core of cell metabolism, are important organelles for iron metabolism, lipid metabolism and energy metabolism. However, it remains controversial debates as how mitochondria participate in ferroptosis and the underlying mechanisms during its progression. This review summaries the current understanding of the occurrence and defense mechanisms of ferroptosis, and the role of mitochondria in promoting and inhibiting ferroptosis, which includes the tricarboxylic acid cycle and glycolysis, reactive oxygen species, and lipid metabolism in mitochondria and their roles in driving ferroptosis. Moreover, we also summarize the defense mechanisms against ferroptosis through detoxification of mitochondrial lipid peroxidation by mitochondrial dihydroorotate dehydrogenase, as well as mitochondrial ferritin. Other mitochondrial molecules and their regulation of ferroptosis is stated at the end. This paper reviews the latest research progress of mitochondria in the process of ferroptosis, which aims to further understand the function of mitochondria in ferroptosis and its mechanism in the occurrence and development of ferroptosis, and therefore provides a theoretical foundation for the basic research of cell biology and strategies for investigation of clinical diseases.
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Aim To explore the mechanism by which total coumarins in Pileostegia tomentella (TCPT) inhibits the proliferation of small cell lung cancer (SCLC) H1688 cells via inducing ferroptosis. Methods The gradient concentrations of TCPT were used to treat H1688 cells. CCK-8 assay was applied for detection of proliferative inhibition of H1688 cells. Transmission electron microscopy was used to approach the morphological changes of H1688 cells under the treatment of TCPT. Additionally, dichlorofluorescein (DCFH-DA) probe was used to detect the intracellular reactive oxygen species (ROS) level. BODIPY 581/ 589 Cll probe was applied to examine the intracellular lipid peroxide formation. Western blotting was employed to detect the expression levels of glutathione peroxidase 4 (GPX4), kelch-like ECH-associated protein (KEAP1), nuclear factor E2 related factor 2 (NRF2), ferritin heavy chain 1 (FTH1) proteins in HI688 cells. Results The proliferation of small cell lung cancer cell H1688 was dramatically inhibited after TCPT intervention (P < 0. 05, P < 0. 01). The morphological characteristics of ferroptosis induced by TCPT were observed by transmission electron microscope. TCPT could also effectively elevate intracellular level of ROS and lipid peroxide. In HI688 cells the expression of ferroptosis markers GPX4, NRF2, and FTH1 was down-regulated, while the expression of KEAP1 was up-regulated, and there were statistically significant differences among the markers mentioned a-bove (P<0. 01). Conclusions Total coumarins in TCPT can significantly inhibit the proliferation of H1688 cells, possibly through increasing ROS and intracellular lipid peroxide levels and eventually inducing ferroptosis.
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Background Dibutyl phthalate (DBP) is a common plasticizer in daily life and has been proved to be related to the exacerbation of allergic asthma. Domestic and foreign studies have shown that lipid peroxidation is closely related to the severity of asthma, which can be used as a basis for the diagnosis and treatment of asthma. Whether DBP can induce lipid peroxidation in allergic asthma remains to be further studied. Objective To investigate whether DBP aggravates allergic asthma by inducing lipid peroxidation in allergic asthma mice. Methods Eighty male BALB/c mice were randomly divided into 4 groups, namely control group, DBP group (40 mg·kg−1), 50 μg ovalbumin (OVA) group (allergic asthma model group), and DBP+OVA group. The DBP group and the DBP+OVA group were given DBP by gavage from Day 1 to 28, and the OVA group and the DBP+OVA group were sensitized by intraperitoneal injection of OVA, once every 3 d, a total of 5 injections, from Day 9 to 21. From Day 29 to 35, the OVA group and the DBP+OVA group were challenged by OVA atomization. After the exposure, samples of blood and lung were collected. The airway hyperresponsiveness of mice was observed by lung function analysis. The serum contents of immunoglobulin E (IgE), OVA-specific immunoglobulin E (OVA-IgE), and lung homogenate levels of interleukin 4 (IL-4) were detected by enzyme-linked immunosorbent assay (ELISA) to evaluate airway allergic inflammation. The pathological changes of lung tissues were observed after hematoxylin-eosin (HE) staining and collagen fiber (Masson) staining. The contents of reactive oxygen species (ROS), lipid ROS, glutathione peroxidase 4 (GPX4), reduced glutathione (GSH), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) in lung homogenates were detected by ELISA to evaluate lipid peroxidation. Results The results of lung function analysis showed that compared with the control group, the inspiratory resistance (Ri) and expiratory resistance (Re) of the OVA group and the DBP+OVA group were increased, and the lung compliance (Cldyn) was decreased. The DBP + OVA group was more severe, and the difference between the OVA group and the DBP + OVA group was statistically significant (P<0.05 or P<0.01). Compared with the control group, the contents of IgE, OVA-IgE, and IL-4 in the OVA group and the DBP+OVA group were increased (P<0.05 or P<0.01), which indicated more severe allergic airway inflammation. The HE sections of the OVA group and the DBP+OVA group showed inflammatory cell infiltration around the airway, airway wall hyperplasia and thickening, and severe airway deformation, and the presentation of the DBP+OVA group was the most serious. After Masson staining, the OVA group and the DBP+OVA group showed depositions of a large number of collagen fibers, and the blue collagen fibrosis in the DBP+OVA group was even more serious. ROS, lipid ROS, MDA, and 4-HNE levels increased and GSH and GPX4 levels decreased in the OVA and DBP+OVA groups (P<0.05 or P<0.01), with the most severe effect in the DBP+OVA group. Conclusion DBP may induce lipid peroxidation in mice allergic asthma by producing excessive ROS which may aggravate the allergic asthma in mice.
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@#Ferroptosis is a newly discovered method of programmed cell death. Current studies have shown that activation of ferroptosis-related pathways can inhibit the growth and proliferation of tumor cells and reverse their drug resistance. Oral cancer is a common malignant tumor with a high recurrence rate and high drug resistance. Inducing ferroptosis is a potential treatment strategy. There are still many uncertainties in the application of ferroptosis in the treatment of oral cancer, which need to be further explored. This article systematically introduces the mechanism of ferroptosis and its recent progress in oral cancer treatment to provide new mechanisms and methods for the clinical treatment of oral cancer. Current research shows that the mechanism of ferroptosis is mainly related to amino acid metabolism, Fe2+ metabolism, and lipid metabolism. Ferroptosis in oral cancer cells can reverse drug resistance in cancer cells and improve the activity of immune cells. New drugs, such as curcumin analogs and triptolide, can induce ferroptosis in oral cancer, and the development of nanomaterials has improved the utilization rate of drugs. Inhibiting the expression of the ferroptosis-related factors SLC7A11, NF-E2-related factor 2 (Nrf2), and ferritin heavy chain 1 (FTH1) can promote ferroptosis in oral cancer cells. It is a potential target for the clinical treatment of oral cancer, but its translation into clinical practice still needs further research.
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Ferroptosis is a pattern of non-apoptotic cell death characterized by iron dependence and lipid peroxidation. Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease with fat infiltration as its main pathological feature, and it is closely associated with insulin resistance and genetic susceptibility. The mechanism of transition from hepatic steatosis alone to steatohepatitis remains unclear, and studies have shown that ferroptosis in hepatocytes may be the trigger for the inflammatory initiation of steatohepatitis. This article reviews the role of abnormal iron metabolism and lipid peroxidation in promoting the development and progression of NAFLD and summarizes the application prospect of ferroptosis-related inhibitors in the treatment of NAFLD.
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In metabolic diseases, the accumulation of reactive oxygen species and oxidative stress are closely associated with ferroptosis. As a key regulatory factor, the imbalance between glycolysis and fatty acid metabolism can participate in ferroptosis directly or indirectly, thereby regulating the occurrence and development of various metabolic diseases. The essence of ferroptosis is a new regulatory cell death mode, which is caused by the excessive accumulation of iron-dependent lipid peroxide. It is closely related to glycolysis and fatty acid metabolism, which plays an important role in metabolic diseases. This regulatory cell death mode is significantly distinguished from other programmed cell death modes and has unique changes in cell morphology, symbolic characteristics and mechanisms. This paper first illustrates the main mechanism of glycolysis and fatty acid metabolism imbalance in the occurrence of ferroptosis, then reviews the research progress of ferroptosis in tumor, diabetes, rheumatoid arthritis and other metabolic diseases, and finally reveals the internal connection between glycolysis-fatty acid metabolism imbalance and ferroptosis, as well as its impacts on metabolic diseases, which provide new strategies for the prevention and treatment of metabolic diseases.
ABSTRACT
Objective To evaluate the protective effect and the underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) on radiation-induced liver injury and liver cell line injury in mouse models. Methods C57BL/6 mice were randomly divided into the blank group, model group and MSC-EV treatment group (treatment group), with 9 mice in each group. AML12 cells were randomly divided into the control group, irradiation group and MSC-EV intervention group (intervention group). Animal and cell models with radiation-induced injury were established by one-time 15 Gy and 6 Gy X-ray irradiation, respectively. At 48 h after irradiation, liver tissues and serum samples of mice were collected and prepared for subsequent experiments. At 15 h post-irradiation, cell experiment was carried out. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and content of malondialdehyde (MDA) in liver tissues and cells were measured. The relative expression levels of interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β and CXC chemokine ligand (CXCL)10 messenger RNA (mRNA) were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Liver tissues were prepared for hematoxylin-eosin (HE) staining to calculate liver pathological injury score. The apoptosis of liver tissues and cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and propidiumiodide (PI) staining, respectively. The expression levels of glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) proteins were detected by Western blot. The production level of reactive oxygen species (ROS) was detected by dihydroethidine (DHE) staining. The fluorescence intensity of mitochondrial permeability transition pore (mPTP) was determined. Results Compared with the blank group, serum levels of AST and ALT were up-regulated, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the mouse liver tissues were up-regulated, and MDA content was increased, liver injury score was elevated, cell apoptosis rate was increased, intracellular ROS level was elevated, and the relative expression levels of GPX4 and FSP1 proteins in the mouse liver tissues were down-regulated in the model group, and the differences were statistically significant (all P<0.05). Compared with the model group, serum levels of AST and ALT were decreased, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the liver tissues of mice were down-regulated, MDA content was declined, liver injury score was declined, cell apoptosis rate was decreased, intracellular ROS level was decreased, and the relative expression levels of GPX4 and FSP1 proteins in the liver tissues of mice were up-regulated in the treatment group, and the differences were statistically significant (all P<0.05). Compared with the control group, cell apoptosis rate was increased, intracellular ROS level was elevated, the fluorescence intensity of mPTP was weakened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were up-regulated, MDA content was increased, and the relative expression levels of GPX4 and FSP1 proteins were down-regulated in the irradiation group, and the differences were statistically significant (all P<0.05). Compared with the irradiation group, cell apoptosis rate was declined, intracellular ROS level was decreased, the fluorescence intensity of mPTP was strengthened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were down-regulated, MDA content was decreased and the relative expression levels of GPX4 and FSP1 proteins were up-regulated in the intervention group, and the differences were statistically significant (all P<0.05). Conclusions MSC-EV may effectively alleviate radiation-induced liver injury by reducing ferroptosis of liver cells, enhancing antioxidant level and decreasing the production of lipid peroxide, thereby effectively alleviating radiation-induced liver injury.