Impact of dietary oils and fats on lipid peroxidation in liver and blood of albino rats

Objective:To investigate the effects of different dietary fat and oils(differing in their degree of saturation and unsaturation)on lipid peroxidation in liver and blood of rats.Methods:The study was conducted on SO albino rats that were randomly divided into 5 groups of 10 animals.The groups were fed on dietary butter(Group I),margarine(Croup II),olive oil(Group III),sunflower oil(Group IV)and com oil(Group V)for 7 weeks.After 12 h of diet removal,livers were excised and blood was collected to measure malondialdehyde(MDA)levels in the supernatant of liver homogenate and in blood.Blood superoxide dismutase activity(SOD),glutathione peroxidase activity(GPx),serum vitamin E and total antioxidant capacity(TAC)levels were also measured to determine the effects of fats and oils on lipid peroxidation.Results:The results indicated that no significant differences were observed in SOD activity,vitamin E and TAC levels between the five groups.However,there was significant decrease of GPx activity in groups IV and V when compared with otlier groups.The results indicated that feeding corn oil caused significant increases in liver and blood MDA levels as compared with other oils and fats.There were positive correlations between SOD and GPx,vitamin E and TAC as well as between GPx and TAC(r:0.743;P<0.001)and between blood MDA and liver MDA(r:0.897;P<0.00l).The results showed also negative correlations between blood MDA on one hand and SOD,GPx,vitamin E and TAC on the other hand.Conclusions:The results demonstrated that feeding oils rich in polyunsaturated fatly acids(PUFA)increases lipid peroxidation significantly and may raise the susceptibility of tissues to free radical oxidative damage.

Dynamic Changes in Lipid Peroxidation and Antioxidant Level in Rat’s Tissues with <i>Macrovipera</i><i>lebetina</i><i>obtusa</i>and <i>Montivipera</i><i>raddei</i>Venom Intoxication

We investigated the balance of free radicals in different tissues (liver, heart, brain and muscle) of rats in course of in vivo and in vitro processing by Macrovipera lebetina obtusa (MLO) and Montivipera raddei (MR) snake venoms. Chemiluminescence (ChL) levels were examined in tissue assays after incubation (at 37 &#176C for a period of 10 min) with venom for in vitro experiments and in tissue assays isolated of 10 min after venom injection for in vivo experiments. The TBA-test was also performed to confirm the free radical expression. The activities of antioxidant enzymes (such as superoxide dismutase and glutathione peroxidase) in isolated tissues were detected by spectro-photometry. During the in vitro processing chemiluminescence levels of tissue homogenates significantly decreased, while in course of in vivo intoxication the level of ChL was elevated in brain and liver;lipid peroxidation also increased in brain tissue, but there was no significant balance change in other tissues;the activity of superoxide dismutase mainly correlated with changes of free radical balance during intoxication. On the contrary, the activity of glutathione peroxidase showed the reverse tendencies to change. We suggest that free radicals and their oxidative stresses may play a role in the early stage of intoxication causing the so-named “spreading-effect”, which is very characteristic for the venom of vipers.

Changes of Selenium Metabolism Glutathione Peroxidase Activity and Lipid Peroxides Content in Severely Scalding-injured Rats

The changes of sclenium metabolism, glutathione peroxidase activity and lipid peroxidescontent in the tissues of rats suffering from 30% TBSA full thickness scalding were observed in thefirst 7 days after injury. It was found that selenium content in the rat tissues decreased remarkably af-ter injury, which in turn resulted in serious reduction of glutathione peroxidasc activity and significantincrease of lipid peroxides in the scrum, crythrocytcs and liver. However the muscular tissue showedno significant changes. These facts imply that after burn injury, the body is in a state of selenium deficiency, the lossof selenium might be responsible for the reduction of anti - peroxidation ability of glutathioneperoxidase, and conscqucntly there is an increase of lipid peroxides in the tissues. Only the musculartissue is insensitive to lipid peroxidation. It is believed that the reduction of anti-peroxidation abilityof glutathione peroxidasc after bum injury might be one of the main causes to intensify, the injury re-suiting from free radicals.

Acute Toxicity of Cadmium on the Antioxidant Defense Systems and Lipid Peroxidation in the Juveniles of Genetically Improved Farmed （GIFT） Tilapia Oreochromis Niloticus

Heavy metals pose a potential threat to aquatic organisms. In this study, a static-renewal acute toxicity test was conducted to investigate the effects of cadmium on the antioxidant defense systems （both enzymatic and non-enzymatic） and lipid peroxidaton in liver and gill tissues of juvenile GIFT tilapia Oreochromis niloticus. After 8 days of exposure to Cd （0, 0.016, 0.08, 0.4 and 2 mg/L）, livers accumulated significantly more Cd than gills. Catalase （CAT）, superoxide dismutase （SOD） and glutathione S-transferase （GST） activities were stimulated only at the highest concentration tested （2 mg/L）. Glutathione peroxidase （GPx） activity was stimulated in the gill while inhibited in the liver, these alternations in gill and liver showed a strong relationship with Cd levels in these tissues. This may indicate either a tissue-specific response of GPx to Cd or, most probably, a hormetic effect of Cd on GPx. Cd increased GSH levels and decreased the ratio GSSG/GSH in fish livers at 2 mg/L. Cd exposure resulted in an elevated level of MDA in the livers of fish at 2 mg/L, indicating that Cd caused lipid peroxidation. Taken together, the results demonstrated that Cd altered the enzymatic and non-enzymatic defensive systems and caused lipid peroxidation in O. niloticus at relatively high concentrations （compared to environmentally relevant concentrations）. In addition, the results implied that O. niloticus could tolerate high level of Cd in sites polluted by Cd.

Flavonoids Reduce Lipid Peroxides and Increase Glutathione Levels in Pooled Human Liver Microsomes (HLMs)

The effects of each of the flavonoids;genistein (G), quercetin (Q) and kaempferol (K) at several doses on lipid peroxides (LP) and reduced glutathione (GSH) in pooled human liver microsomes (HLMs) were investigated following the oxidative damage for 4, 6, 18 and 24 hr. HLMs (1 mg/ml) were exposed to each of the above flavonoids at 0, 5, 10, 15, 20 or 25 μM and incubated for the respective times as previously stated. Our hypothesis was that HLMs exposed to the flavonoids for the respective exposure times can decrease LP and increase GSH in HLMs to better cope with the oxidative stress. The results of our studies indicate that each of the flavonoids significantly (p < 0.01) decreased LP compared to their respective controls. The highest decrease in LP was observed for K followed by Q and G. Significant increases (p < 0.01) in GSH were observed for the flavonoid doses tested with the highest levels observed for Q for the 24-hr. incubation. The findings suggest that the flavonoids modulate oxidative stress in HLMs by decreasing LP and such decreases in LPs may be due to the increasing and or the replenished levels of GSH in the said cells to better cope with the oxidative stress.

Effect of Nicotine on Dopamine and Glutathione Levels in Presence of Oligoelements in Brain Regions of Young Rats——Effect of Nicotine on Brain Regions of Rat

Aim: The purpose of this study was to understand the mechanism of nicotine mediated addiction and the role of oligoelements in reducing its effect. Methods: Male Wistar rats (weight 80 g) were treated with single and repeated doses of nicotine and/or oligoelements as follows: group 1 (control) NaCl 0.9%;group 2, nicotine (1 mg/kg);group 3, oligoelements (50 μl/rat);and group 4, nicotine (1 mg/kg) + oligoelements (50 μl/rat). All drugs were intraperitoneally administered for 4 days. Blood for the measurement of glucose was obtained from all the animals. Samples of the brain regions (cortex, hemispheres and cerebellum + medulla oblongata) of each rat were obtained and used to measure the concentrations of dopamine, GSH levels, and lipid peroxidation (TBARS) using fluorescence and spectrophotometric methods. Results: Glucose level increased in rats treated with nicotine and oligoelements (p < 0.05), while GSH level decreased in cerebellum/medulla oblongata and hemispheres (p < 0.05) of the same animals. TBARS levels increased in cerebellum/medulla oblongata and hemispheres of animals treated with nicotine and oligoelements, but decreased in the same regions (p < 0.05) in rats treated only with oligoelements. The levels of dopamine decreased in cortex and hemispheres, but increased in cerebellum/medulla and oblongata regions of rats treated with both compounds (p < 0.05). Conclusions: Nicotine and oligoelements are associated with increase in the level of glucose, an effect that was more pronounced in the group treated with both drugs. Reduction of oxidative stress and dopamine metabolism may be involved in this effect.

Effects of Selenium on Lipid Peroxidation and Oxidizing Ability of Rice Roots under Ferrous Stress

Water culture experiment was conducted to study the effects of selenium(Se) on glutathione peroxidase(GSH-Px) activity,reduced glutathione(GSH) concentration and the accumulation of malonaldehyde(MDA),the product of lipid peroxidation in rice seedling,as well as the effect of se on oxidizing ability of roots under ferrous stress.Results showed that appropriate amount of se significantly increased GSH-Px activity in rice leaves,F=5.5 *,enhanced the amount of GSH and oxidizing ability of roots and reduced the concentration of MDA,F=4.9 *.Compared with Se0+Fe treatment,Se treatments increased the dry matter weight of rice seedling from 10.06% to 10.43%,F=4.09 *.

CLINICAL SIGNIFICANCE OF VITAMIN C TO AMELIORATE LIPID PEROXIDATION DAMAGE IN CORONARY ARTERY DISEASE

The activities of superoxide dismutase (SOD). glutathione peroxidase (GSH-PX) in blood and the content of melondialdehyde (MDA) in plasma of 30 Fatients (male 17, female 13) with coronary artery disease (CAD) were determined in this study. It was shown that SOD and GSH-PX activities were decreased and the content of MDA was increased in the Patients comparative with the healthy controls (P<0.001). Vitamin C, the free radical scavenger, was then administered intravenously with a daily dose of 2g for 2 weeks. The activities of SOD and GSB-PX were significantly elevated (P<0.01, and P<0.05, respectively). and the level of MDA was obviously declined (P<0.01). Thus,the lipid peroxidation is involved in the pathogenesis of CAD,and vitamin C possessing some effects to ameliorate the lipid peroxidation damage could be helpful in the treatment of CAE.

还原型谷胱甘肽注射液联合高压氧治疗一氧化碳中毒伴心肌损伤的效果及对心肌损伤的保护作用

目的 研究还原型谷胱甘肽注射液联合高压氧治疗一氧化碳中毒伴心肌损伤的效果及对心肌损伤的保护作用。方法 选取2020年1月—2023年1月收治的一氧化碳中毒伴心肌损伤108例,采用随机数字表法分为观察组和对照组各54例。全部患者实施高压氧治疗,观察组患者则加用还原性谷胱甘肽注射液治疗,2组患者均治疗2周。观察2组患者的治疗效果、血清学指标及心肌指标,以及2组患者不良反应情况。结果 观察组患者治疗总有效率(90.74%,49/54)较对照组(79.53%,41/54)高(P<0.05)。治疗后,2组患者超氧化物歧化酶、谷胱甘肽过氧化物酶水平上升,而脂质过氧化物、丙二醛、肌酸激酶、心肌型肌酸激酶同工酶、天冬氨酸转氨酶、心肌肌钙蛋白T水平下降,且观察组患者上述指标水平改变幅度高于对照组(P<0.05)。治疗后,观察组患者心电图异常率显著低于对照组(P<0.05)。2组患者不良反应比较差异无统计学意义(P>0.05)。结论 还原型谷胱甘肽注射液联合高压氧治疗一氧化碳中毒伴心肌损伤的效果显著,对于心肌细胞损伤具有显著的改善作用。

Ferroptosis mechanism and Alzheimer's disease

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.

Metformin alleviates spinal cord injury by inhibiting nerve cell ferroptosis through upregulation of heme oxygenase-1 expression

Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury models.Heme oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox homeostasis.Metformin is a classic drug used to treat type 2 diabetes that can inhibit ferroptosis.Previous studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 expression.Therefore,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord injury.To test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord injury.Next,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell ferroptosis.Continuous intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord injury.Subsequently,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord injury.Taken together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.

铁死亡及其在实验性急性肺损伤中的作用

作为一种非凋亡性细胞死亡方式,铁死亡的特征是铁依赖性脂质过氧化物积累引起的膜脂质过氧化、线粒体萎缩等,在形态和生化特性上与其他细胞程序性死亡不同。铁死亡受多种代谢通路调控,参与了失血性休克、缺血再灌注、脓毒症、放射等引起的急性肺损伤。本文综述了铁死亡的主要调控机制及其在多种动物模型急性肺损伤发病机制中的作用,以期为防治急性肺损伤提供新的策略。

铁死亡相关途径改善胃肠道恶性肿瘤细胞耐药性的研究进展

目前,临床上对胃肠道恶性肿瘤的治疗仍然以放化疗为主,但是患者对放化疗药物易产生耐药性,严重影响患者的生活质量。研究发现,肿瘤化疗药物的耐药性是由铁的累积和氧化还原稳态失调所造成,也许调控铁死亡途径可以为胃肠道恶性肿瘤耐药的治疗带来新的机遇。本文对铁死亡的特征、调控机制进行了系统的总结与分析,同时概述了铁死亡不同途径对改善胃肠道恶性肿瘤细胞耐药性的研究进展,旨在为胃肠道恶性肿瘤耐药患者的治疗提供新的思路和方向。

中药调控成骨细胞铁死亡治疗激素性股骨头坏死

背景:有研究发现成骨细胞铁死亡可作为重要的发病机制诱导激素性股骨头坏死的发生与发展。随着祖国医学的发展,有学者发现某些中药单体、中药复方及中成药等可通过多种通路机制调控成骨细胞铁死亡,最终起到治疗激素性股骨头坏死的作用。目的:探讨成骨细胞铁死亡与激素性股骨头坏死的关系及中草药调控成骨细胞铁死亡治疗激素性股骨头坏死的作用机制,为激素性股骨头坏死的诊治提供新的思路。方法:以“铁死亡,激素性股骨头坏死,成骨细胞,中草药,糖皮质激素,铁代谢,活性氧,谷胱甘肽过氧化物酶”为中文检索词,以“ferroptosis,Hormonal necrosis of the femoral head,osteoblast,Chinese herbal medicine,glucocorticoid,iron metabolism,ROS,GPX4”为英文检索词,检索中国知网、Pub Med、万方及维普数据库,筛选各数据库建库至2023年成骨细胞铁死亡与激素性股骨头坏死及中草药干预调控研究相关的文章,最终纳入74篇文献进行综述分析。结果与结论:(1)成骨细胞铁死亡在激素性股骨头坏死发病中起重要作用。(2)成骨细胞铁死亡的发生受到多种机制通路调控,如细胞内铁超载引起铁死亡;细胞发生脂质过氧化损伤细胞膜引起铁死亡;细胞膜上胱氨酸/谷氨酸逆向转运蛋白通过影响谷胱甘肽水平和谷胱甘肽过氧化物酶4活性,从而诱导铁死亡;细胞内发生芬顿反应产生大量活性氧引起铁死亡等。(3)中药单体淫羊藿苷等、中药复方青娥丸等及中成药补肾活血颗粒等均可通过调控成骨细胞铁死亡的发生,有助于防治激素性股骨头坏死。(4)目前关于成骨细胞铁死亡相关机制尚不明确,继续深入探明两者的作用机制,有望为临床治疗激素性股骨头坏死提供新选择。

铁死亡与动脉粥样硬化的联系

铁死亡(Ferroptosis)是新近发现的细胞死亡形式,其特征是细胞内铁离子异常积聚和致死性脂质过氧化。这种调节性细胞死亡与铁代谢、氨基酸代谢、脂质代谢等多种代谢途径有着较为密切的联系。动脉粥样硬化是多种心血管疾病发病的基础之一。近期研究表明,除了凋亡、坏死、自噬等经典死亡途径外,铁死亡也参与了动脉粥样硬化的发生发展。本文阐述了铁死亡机制及其对动脉粥样硬化病变相关细胞及因子的影响。

血清谷胱甘肽过氧化物酶、脂质过氧化物水平与妊娠期糖尿病及其糖脂代谢异常、胰岛素抵抗和母婴结局的关系

目的探讨血清谷胱甘肽过氧化物酶(GSH-PX)、脂质过氧化物(Lpo)水平与妊娠期糖尿病(GDM)及其糖脂代谢异常、胰岛素抵抗和母婴结局的关系。方法选择2020年6月至2022年6月重庆大学附属黔江医院收治的120例GDM病人(GDM组)和同期收治的120例糖耐量正常的孕产妇(对照组)。检测血清GSH-Px、Lpo水平以及糖脂代谢、胰岛素抵抗指标,追踪母婴结局。Pearson分析GSH-Px、Lpo与糖脂代谢、胰岛素抵抗之间相关性,多因素logistic回归分析GDM母婴结局不良的因素。结果GDM组血清GSH-Px水平[(21.05±3.46)U/g比(30.42±5.09)U/g]低于对照组(P<0.05),Lpo水平[(15.95±3.17)μmol/L比(10.61±2.33)μmol/L]高于对照组(P<0.05)。GDM病人血清GSH-Px水平与总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)呈负相关(P<0.05),与高密度脂蛋白胆固醇(HDL-C)呈正相关(P<0.05);Lpo水平与TC、TG、LDL-C、FPG、FINS、HOMA-IR呈正相关(P<0.05),与HDL-C呈负相关(P<0.05)。120例GDM病人中45例发生母婴结局不良,母婴结局不良组血清GSH-Px水平低于母婴结局良好组(P<0.05),Lpo水平高于母婴结局良好组(P<0.05)。多因素logistic回归分析结果显示年龄、HOMA-IR、Lpo是GDM病人母婴结局不良的危险因素(P<0.05),GSH-Px是GDM病人母婴结局不良的保护因素(P<0.05)。结论GDM病人血清GSH-Px水平降低,Lpo水平增高,且与糖脂代谢紊乱、胰岛素抵抗以及母婴结局不良有关,检测血清GSH-Px、Lpo水平有助于评估GDM胰岛素抵抗状态和母婴结局风险。

铁死亡在急性肾损伤中作用及机制的研究进展

铁死亡是一种新型的调节细胞死亡的策略,其发生过程与细胞内的铁代谢、脂质代谢、氨基酸代谢以及多种信号通路有密切联系。铁死亡在急性肾损伤(AKI)的发病机制中起关键作用。铁死亡可能是治疗缺血再灌注损伤、肾毒性药物、横纹肌溶解综合征、脓毒症等多种原因引起的AKI的重要靶点。本文就铁死亡的调控机制及其在AKI中作用的研究进展予以综述。

铁死亡在溃疡性结肠炎中的研究进展

溃疡性结肠炎(UC)是一种慢性炎症性肠病,特征为肠道黏膜的持续炎症和溃疡形成,其发病机制涉及免疫功能障碍、肠道微生物群失调和炎症所引起的黏膜损伤。铁死亡是一种铁依赖性细胞死亡形式,其调控机制包括铁代谢紊乱、脂质过氧化和谷胱甘肽(GSH)耗竭。已有研究表明,铁死亡在UC的发病过程中起关键作用,特别是在调节炎症反应和损伤肠道上皮细胞方面。本文综述了铁死亡的调控机制及其在UC中的作用,探讨了通过调节铁代谢、减少脂质过氧化和维护GSH水平来缓解UC症状的潜在治疗策略,为UC的诊断和治疗提供了新的靶点和方向。

铁死亡的分子机制及其对膀胱癌的影响

膀胱癌(bladder cancer,BC)是泌尿系统三大常见恶性肿瘤之一,具有发病率高、易转移、治疗效果不佳、预后较差的特点,严重威胁着全人类的健康。肿瘤细胞表现出强烈的需铁现象,而铁超载会诱导细胞发生铁死亡,即一种由脂质过氧化和细胞膜损伤引起的铁依赖性细胞死亡。因此,铁死亡具有很强的抗肿瘤潜力。铁死亡的分子机制与细胞磷脂代谢异常、铁代谢异常、抗氧化和非抗氧化系统Xc-/谷胱甘肽(glutathione,GSH)/谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)的失调有关。铁死亡相关分子在BC的发生和发展、转移、耐药及免疫反应等方面发挥着重要的作用,有望成为治疗BC的靶点。

铁死亡调控蛋白GPX4的小分子抑制剂研究进展

铁死亡(ferroptosis)是2012年新发现的一种非凋亡坏死的细胞死亡方式,其主要特征为脂质活性氧增多以及细胞内亚铁离子累积。谷胱甘肽过氧化物酶4(GPX4)是含硒GPx家族第4位成员,是细胞清除脂质过氧化物的重要蛋白,也是铁死亡的重要调节因子。靶向GPX4小分子抑制剂能诱导铁死亡发生,为治疗耐药性癌症和神经退行性疾病提供了新的策略。主要介绍GPX4蛋白的结构和功能,并综述GPX4小分子抑制剂最新前沿进展,为开发基于GXP4抑制的铁死亡诱导剂提供研究基础。