Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer

As a highly aggressive tumor,the pathophysiological mechanism of primary liver cancer has attracted much attention.In recent years,factors such as ferroptosis regulation,lipid peroxidation and metabolic abnormalities have emerged in the study of liver cancer,providing a new perspective for understanding the development of liver cancer.Ferroptosis regulation,lipid peroxidation and metabolic abnormalities play important roles in the occurrence and development of liver cancer.The regulation of ferroptosis is involved in apoptosis and necrosis,affecting cell survival and death.Lipid peroxidation promotes oxidative damage and promotes the invasion of liver cancer cells.Metabolic abnormalities,especially the disorders of glucose and lipid metabolism,directly affect the proliferation and growth of liver cancer cells.Studies of ferroptosis regulation and lipid peroxidation may help to discover new therapeutic targets and improve therapeutic outcomes.The understanding of metabolic abnormalities can provide new ideas for the prevention of liver cancer,and reduce the risk of disease by adjusting the metabolic process.This review focuses on the key roles of ferroptosis regulation,lipid peroxidation and metabolic abnormalities in this process.

Mechanisms and active substances of targeting lipid peroxidation in ferroptosis regulation

Ferroptosis is a novel form of cell death driven by iron-dependent lipid peroxidation and it is implicated in various diseases,such as liver disease,acute kidney injury,cardiovascular disease,neurodegenerative disease and cancer.Lipid-based reactive oxygen species(ROS),particularly lipid hydroperoxides in the cellular membrane can lead to membrane disruption and cell death mediated by ferroptosis.There are three necessary stages involving in the process of lipid peroxidation regulation in ferroptosis,including the synthesis of membrane phospholipids,initiation of lipid peroxidation and clearance of lipid peroxides.In this review,we summarized the molecular modulation mechanisms of lipid peroxidation in ferroptosis from the above three stages,as well as various ferroptosis modulators targeting lipid peroxidation,including commonly used products,natural bioactive compounds and selenocompounds.Collectively,these findings suggest the vital role of lipid peroxidation in ferroptosis,and targeting lipid peroxidation in ferroptosis is potential to treat ferroptosis-associated diseases.

Correction to“Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence of primary liver cancer”

Correction to“Research progress of ferroptosis regulating lipid peroxidation and metabolism in occurrence and development of primary liver cancer”in World J Gastrointest Oncol 2024;16:2335-2349,published by Shu YJ,Lao B,and Qiu YY.In this article,we added the correct citations of images.

Ferroptosis regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer

BACKGROUND Gastric cancer is one of the most common malignant tumors in the world,and its occurrence and development involve complex biological processes.Iron death,as a new cell death mode,has attracted wide attention in recent years.However,the regulatory mechanism of iron death in gastric cancer and its effect on lipid peroxidation metabolism remain unclear.AIM To explore the role of iron death in the development of gastric cancer,reveal its relationship with lipid peroxidation,and provide a new theoretical basis for revealing the molecular mechanism of the occurrence and development of gastric cancer.METHODS The process of iron death in gastric cancer cells was simulated by cell culture model,and the occurrence of iron death was detected by fluorescence microscopy and flow cytometry.The changes of gene expression related to iron death and lipid peroxidation metabolism were analyzed by high-throughput sequencing technology.In addition,a mouse model of gastric cancer was established,and the role of iron death in vivo was studied by histology and immunohistochemistry,and the level of lipid peroxidation was detected.These methods comprehensively and deeply reveal the regulatory mechanism of iron death on lipid peroxidation metabolism in the occurrence and development of gastric cancer.RESULTS Iron death was significantly activated in gastric cancer cells,and at the same time,associated lipid peroxidation levels increased significantly.Through high-throughput sequencing analysis,it was found that iron death regulated the expression of several genes related to lipid metabolism.In vivo experiments demonstrated that increased iron death in gastric cancer mice was accompanied by a significant increase in lipid peroxidation.CONCLUSION This study confirmed the important role of iron death in regulating lipid peroxidation metabolism in the occurrence and development of gastric cancer.The activation of iron death significantly increased lipid peroxidation levels,revealing its regulatory mechanism inside the cell.

Chlorophyll Fluorescence and Membrane Lipid Peroxidation in the Flag Leaves of Different High Yield Rice Variety at Late Stage of Development Under Natural Condition

With indica ( Oryza sativa L.) hybrid Shanyou 63 as control, the hybrid rice varieties including Peiai 64S/E32, Peiai 64S/9311, X07S/Zihui 100, Guangyou 881 and japonica 9516 were used to study changes of chlorophyll content, photosynthetic response to light intensity and temperature, chlorophyll fluorescence characteristics and membrane lipid peroxidation in their flag leaves at the late stage of development under natural conditions in Nanjing. The results were as follows:. primary photochemical efficiency of PS II ( F-v / F-m), quantum yield of linear electron transport of PS II (phi(PSII)), electron transfer rate (ETR) in these rice varieties decreased with their decrease of chlorophyll content during this period. This kind of impediment to energy conversion induced the transfer of excessive energy to the reducing side of PS I, hence the accumulation of O-2(radical anion) and peroxidation of membrane lipid, and resulting in the accumulation of malondialdehyde (MDA), that is the destroys of photosynthetic pigments and membranes and the consequent, premature senescence. This phenomenon is variable conspicuously in different rice varieties. Under natural condition in Nanjing, F-v/F-m, phi(PSII), ETR and quenching coefficient ( qP) in japonica 9516 tolerant to photooxidation decreased less and the conversion capacity of light energy was stable, premature senescence was unlikely, and consequently the seed-setting rate was higher. While F-v/F-m, phi(PSII), ETR and photochemical qP in Shanyou 63 sensitive to photooxidation decreased more and therefore premature senescence was easy to happen, thus the seed-setting rate and yield were all reduced. The tolerance to photooxidation and premature senescence in other hybrids derived from typical two line or three line crossing laid in the middle. From the rice breeding for super-high-yield, on the basis of the good plant-type of current rice, considering both hybrid vigor and the prevention premature senescence, it would be a notable strategy to use japonica maternal line or maternal. lines with some japonica genotype as the sterile lines in rice breeding.

Responses of Membrane Lipid Peroxidation and Endogenous Hormones of Soybean Seedlings to UV-B Radiation and Rare Earth

[ Objective] The aim was to provide strategies for development of rare earth and control of environmental pollution. [ Method] Responses of membrane lipid peroxidation and endogenous hormones of soybean seedlings to UV-B radiation and rare earth were studied through hydroponics in laboratory. [ Result] The results showed that under irradiation of UV-B（ T1-0.15 W/m^2 and T2-0.45 W/m^2）, chlorophyll and indole-3-acetic acid（IAA） contents firstly decreased during the stress phase （1 -5 d） and then increased during the restoration phase （6 -9 d） while contents of malonadialdehyde（MDA） and abscisic acid（ABA） gradually increased during the imposition of UV-B radiation （1 -5 d） and subsequently decreased during recovery from UV-B stress （6 -9 d） . With adding of La （III） with the concentration of 20 mg · L^-1 , the decline/dse trend of chlorophyll, IAA, MDA and ABA contents was slowed down during the stress period while the rise/decline speed was accelerated during the recovery period. [ Conclusion] It suggests that the regulation of La （ III ） on membrane lipid peroxidation and endogenous hormones could increase chlorophyll and IAA contents, improve the metabolism of reactive oxygen species （ ROS）, inhibit membrane lipid peroxidation, decrease the accumulation amount of ABA and alleviate injury of UV-B radiation to soybean seedlings. Further, the protective potential of La （ III ） was better under low UV-B radiation than under high one.

Photochemical Efficiency of PSⅡ and Membrane Lipid Peroxidation in Leaves of indica and japonica Rice (Oryza sativa) Under Chilling Temperature and Strong Light Stress Conditions

Relationships between fluorescence parameters and membrane lipid peroxidation in leaves of indica and japonica rice (Oryza sativa L.) during later growth stage were studied under chilling temperature and strong light stress conditions. Results showed that D1 protein contents of PSⅡ in photosynthetic apparatus dropped, the generation of antheraxanthin (A) and zeaxanthin (Z) of xanthophyll cycle were inhibited partly, PSⅡ photochemical efficiency (F v/F m)and non-photochemical quenching (q N) were also decreased obviously. In addition, endogenous active oxygen scavenger—superoxide dismutase (SOD) reduced, superoxide anion radical (O -· 2) and malondialdehyde (MDA) accumulated, as a result, photooxidation of leaves occurred under chilling temperature and strong light stress conditions. Obvious differences in the changes of the above mentioned physiological parameters between indica and japonica rice were observed. Experiments in leaves treated with inhibitors under chilling temperature and strong light conditions showed that indica rice was more sensitive to chilling temperature with strong light and subjected to photooxidation more than japonica rice. Notable positive correlation between D1 protein contents and F v/F m or (A+Z)/(A+Z+V), and a marked negative correlation between F v/F m and MDA contents were obtained by regression analysis in indica and japonica rice during chilling temperature and strong light conditions. According to the facts mentioned above, it was inferred that PSⅡ photochemical efficiency(F v/F m) was the key index to forecast for the prediction of photooxidation under stress circumstances and the physiological basis were the synthetic capacity of D1 protein and the protection of xanthophyll cycle.

Effects of Water─soluble Components Isolated from Salviamilltiorrhiza on Oxygen Free Radical Generation and LipidPeroxidation

The effects of water─soluble components isolated from Salvia miltiorrhiza on oxygen free radical prodction and lipid peroxidation were estimated. Five components(10 μmol/L)were shown to inhibit superoxide anion generation by xanthine─xanthine oxidase system. It was also demonstrated that six components( 100 μmol/L) prevented H_2O_2─induced hemolysis and MDA fonnation in mouse erythrocytes.The effects of Sal A, Sal B, Sal C and Ros A were dose dependent. In Langendorff rat heart, pretreatment with Sal A 20μmol/L significantly prevented MDA production induced by 30 min reoxygenation after 45 min anoxia.The results indicated that there were also other potent antioxidant componentts in Salvia milliorrhiza besides Dphl and Pal. The protection of Sal A against myocardial anoxiareoxygenation inury may be mainly ascribed to its oxygen free radical scavenging activity.

Effects of Exogenous Nitric Oxide on Membrane Lipid Peroxidation in Wheat Seeding Exposed to Enhanced Ultraviolet-B Radiation

[Objective] Effects of different concentrations of nitric oxide on membrane lipid peroxidation of wheat induced by enhanced UV-B radiation were researched,sodium nitroprusside （SNP） was selected as an exogenous nitric oxide（NO）donor.[Method] There are 3 groups including CK,UV treatment group （B）,B＋SNP treatment group,0,1,2,3,4 d sampling after treatment respectively,and physiological and biochemical indexes of MDA content and CAT,POD,SOD and so on were determined,repeated 3 times,and statistical analyzed.[Result] The results showed that,after the enhanced UV-B radiation,activity of the catalase （CAT）,superoxide dismutase （SOD） and of the guaiacol peroxidase （POD） all reduced apparently,and the concentration of malondialdehyde （MDA） increased obviously,leading to oxidative damage in wheat seedlings.Impose different concentrations of SNP after UV-B radiation,may mitigate oxidative damage of wheat seedling from different degrees,which was in agreement with the effect of making the concentration of MDA decrease and the activity of the CAT,SOD and POD all increased.The mitigation role of 0.01 mol/L SNP was more obvious for roots＇ oxidative damage,while 0.1 mmol/L SNP is more effective for oxidative damage of leaves.[Conclusion] Exogenous NO donor SNP had obvious relieve effects on oxidative damage of wheat seedlings caused by UV-B radiation,which can enhance adaptive capacity of plants to adversity stress.

Study on Antioxidants and Lipid Peroxidation from Pea Crops of Platean

[ Objective] The aim of this study was to discuss the effect of antioxidants and lipid peroxidation from pea crops of plateau. [ Method] SOD enzyme liquid from pea crops of plateau was extracted by means of protein concentration assay, enzyme activity assay and antioxidant activity determination by DPPH method, peroxide activity inhibition of in vitro tissues from mice by homogenate MDA colorimetry method and lipid peroxidation assay of in vitro tissues. [ Result ] IC50 of the crude enzyme liquid extracted from pea on DPPH was 55.16 mg/L, while the scavenging rate of the crude enzyme liquid was lower than that of ascorbic acid, tea polyphenol and citric acid with the same concentration. The synergistic effect was found in ascorbic acid and crude enzyme liquid, but the synergism of ascorbic acid was better than that of citric acid. IC50 of SOD enzyme liquid extracted from pea on DPPH was 11.1 mg/L, which was better than that of tea polyphenol and closely similar to that of ascorbic acid. SOD enzyme liquid extracted from pea had an inhibitory effect on MDA production from in vitro tissues such as liver, kidney and heart, especially for a significantly inhibitory effect on MDA from liver in vitro. When the concentration was 0.25 mg/ml, the inhibition rate reached 78.3%, and then the inhibition rate increased little with the concentration incresas, while its effect on heart and kidney were inferior. [ Conclusion] SOD crude enzyme liquid and SOD enzyme liquid extracted from pea all have certain DPPH scavenging capacity, while SOD enzyme liquid extracted from pea has an inhibitory effect on lipid peroxidation.

The Effects of Captopril and Cicaprost on Changes of Cardiac Membrane Fluidity and Lipid Peroxidation

The main purpose of this study was to investigate the protective actions of captopril and cicaprost on changes of membrane fluidity of cultured neonatal rat myocardial cells exposed to anoxia and sugar deprivation.Lipid peroxidation level estimated by determining the thiobarbituric acid reactive substance(TBARS)content and lactate dehydrogenase(LDH)released in culture medium was also observed in order to examine other membrane-related changes due to anoxia.Membrane fluidity was monitored by measuring changes in the steady state fluorescence anisotropy(r_s)by fluorescence spectroscopy.The r_s value,TBARS level and LDH release were significantly increased after 3 h anoxia.Captopril(180 μmol/L),cicaprost(30 nmol/L)and indomethacin(1μmol/L)did not alter r_s, TBARS level and LDH activity of normal cultured neonatal rat myocardial cells.However,both captopril and cicaprost significantly prevented the increases of r_s,TBARS content and LDH release in those cells exposed to anoxia and sugar deprivation.lndomethacin abolished the actions of captopril on TBARS production and LDH release,but maintained its membrane fluidity protection.These results indicate that captopril and cicaprost protect membrane fluidity and lipid peroxidation changes in anoxia- injured myocardial cells.The action mechanism of captopril may be due,in part,to stimulation of prostacyclin synthesis and/or release.

Mechanisms of Inhibitory Effects of Breviscapine on Lipid Peroxidation in Rat Brain Mitochondria

The mechanisms by which breviscapine (Bre) inhibits the lipid preoxidation in rat brain mitochondria were investigated. The mitochondrial lipid peroxidation of rat brain induced by oxygen free radical was measured by thiobarbituric acid spectrophotometry. The chelating activities of Bre for Fe 2+ were tested by differential spectrum. Superoxide anion (O 2)from xanthine xanthine oxidase (Xan XO) system and hydroxyl radical (·OH) from FeSO 4 H 2O 2 system were determined with spectrophotometry. It was found that Bre could effectively inhibit the lipid peroxidation of brain mitochondria induced by free radicals driven from Xan XO and FeSO 4 H 2O 2 system. The IC 50 of Bre were 93 01 μmol·L -1 for Xan XO system and 62 18 μmol·L -1 for FeSO 4 H 2O 2 system. Bre also scavenged O 2 and ·OH produced by Xan XO and FeSO 4 H 2O 2 systems. The IC 50 of Bre were 32 63 μmol·L -1 for O - 2 and 20 22 μmol·L -1 for ·OH. Furthermore, the chelating Fe 2+ activity of Bre was shown. It may be concluded that Bre inhibited lipid peroxidation at different stages of the reaction of oxygen free redial with the mitochondria membrane: (1) the formation of ·OH; (2) the initiation of the lipid peroxidation, by chelating Fe 2+ and scavenging O 2 as well as ·OH. The scavenging oxygen free radicals and chelating iron are the mechanisms of inhibitory effect of Bre on lipid peroxidation.

Modulatory effect of pineapple peel extract on lipid peroxidation,catalase activity and hepatic biomarker levels in blood plasma of alcoholinduced oxidative stressed rats

Objective:To investigate the ability of the methanolic extract of pineapple peel to modulate alcohol-induced lipid peroxidation,changes in catalase activities and hepatic biochemical marker levels in blood plasma.Methods:Oxidative stress was induced by oral administration of ethanol(20%w/v) at a dosage of 5 niL/kg bw in rats.After 28 days of treatment,the rats were fasted overnight and sacrificed by cervical dislocation.Blood was collected with a 2 mL syringe by cardiac puncture and was centrifuged at 3000 rpm for 10 min.The plasma was analyzed to evaluate malondialdehyde(MDA),catalase activity,aspartate aminotransferase(AST),alkaline phosphatase(ALP) and alanine aminotransferase(ALT) concentrations.Results:Administration of alcohol caused a drastic increase(87.74%) in MDA level compared with the control.Pineapple peel extract significantly reduced the MDA level by 60.16%at 2.S mL/kg bw.Rats fed alcohol only had the highest catalase activity,treatment with pineapple peel extract at 2.5 mL/kg bw however, reduced the activity.Increased AST,ALP and ALT activities were observed in rats fed alcohol only respectively,treatment with pineapple peel extract drastically reduced their activities. Conclusions:The positive modulation of lipid peroxidation,catalase activities as well as hepatic biomarker levels of blood plasma by the methanolic extract of pineapple peels under alcoholinduced oxidative stress is an indication of its protective ability in the management of alcoholinduced toxicity.

Effects of melatonin on lipid peroxidation and antioxidant enzymes in streptozotocin-induced diabetic rat testis

Aim： To examine the effects of melatonin treatment on lipid peroxidation （LPO） and the activities of antioxidant enzymes in the testicular tissue of streptozotocin （STZ）-induced diabetic rats. Methods： Twenty-six male rats were randomly divided into three groups as follows： group Ⅰ, control, non-diabetic rats （n = 9）; group Ⅱ, STZ-induced, untreated diabetic rats （n = 8）; group Ⅲ, STZ-induced, melatonin-treated （dose of 10 mg/kg·day） diabetic rats （n = 9）. Following 8-week melatonin treatment, all rats were anaesthetized and then were killed to remove testes from the scrotum. Results： As compared to group Ⅰ, in rat testicular tissues of grouap Ⅱ, increased levels of malondialdehyde （MDA） （P 〈 0.01） and superoxide dismutase （SOD） （P 〈 0.01） as well as, decreased levels of catalase （CAT） （P 〈 0.01） and glutathione peroxidase （GSH-Px） （P 〉 0.05） were found. In contrast, as compared to group Ⅱ, in rat testicular tissues of group Ⅲ, levels of MDA decreased （but this decrease was not significant, P 〉 0.05） and SOD （P 〈 0.01） as well as CAT （P 〈 0.05） increased. GSH-Px was not influenced by any of the treatment. Melatonin did not significantly affect the elevated glucose concentration of diabetic group. At the end of the study, there was no significant difference between the melatonin-treated group and the untreated group by means of body and testicular weight. Conclusion： Diabetes mellitus increases oxidative stress and melatonin inhibits lipid peroxidation and might regulate the activities of antioxidant enzymes of diabetic rat testes.

Effects of Water Stress on the Protective Enzyme Activities and Lipid Peroxidation in Roots and Leaves of Summer Maize

A systematic study was conducted to determine the effects of water stress on the activities of protective enzymes and lipid peroxidation in maize. The results showed that, under water stress, the activities of superoxide dismutase （SOD）, catalase （CAT）, and peroxidase （POD） in leaves and roots increased sharply at prophase and metaphase growth stages, such as, male tetrad stage, but then declined towards the physiological maturity. The protective enzyme activities in roots were lower than those in leaves. The content of malondialdehyde （MDA） increased according to the severity of water stress. The content of MDA in roots was lower than that in leaves. The activities of protective enzymes and lipid peroxidation in roots were positively related to that in leaves with most of the correlation coefficients being significant. The content of soluble proteins in roots and leaves decreased with increasing drought stress. The ear characteristics deteriorated and the economic yields of maize decreased significantly under water stress. The main factors that caused reduction of yields were the decrease in the number of ear kernels and 100-kernel weight.

Effects of Fluoride on Lipid Peroxidation, DNA Damage and Apoptosis in Human Embryo Hepatocytes

Objective To investigate the effects of fluoride on lipid peroxidation, DNA damage and apoptosis in human embryo hepatocyte L-02 cells. Methods Lipid peroxide (LPO) level, reduced glutathione (GSH) content, DNA damage, apoptosis, and cell cycle analysis were measured after in vitro cultured L-02 cells were exposed to sodium fluoride at different doses (40 μg/mL, 80 μg/mL, and 160 μg/mL) for 24 hours. Results Fluoride caused an increase of LPO levels and a decrease of GSH content in L-02 cells. There appeared to be an obvious dose-effect relationship between the fluoride concentration and the observed changes. Fluoride also caused DNA damage and apoptosis and increased the cell number in S phase of cell cycle in the cells tested. There was a statistically significant difference in DNA damage and apoptosis when comparing the high dose of fluoride treated cells with the low dose of fluoride treated cells. Conclusion Fluoride can cause lipid peroxidation, DNA damage, and apoptosis in the L-02 cell experimental model and there is a significant positive correlation between fluoride concentration and these pathological changes.

Changes of Antioxidative Enzymes and Lipid Peroxidation in Leaves and Roots of Waterlogging-Tolerant and Waterlogging-Sensitive Maize Genotypes at Seedling Stage

To better understand the physiological and biochemical mechanisms of waterlogging tolerance, waterlogging effects on lipid peroxidation and the activity of antioxidative enzymes were investigated in leaves and roots of two maize genotypes, HZ32 （waterlogging-tolerant） and K12 （waterlogging-sensitive）. Potted maize plants were waterlogged at the second leaf stage under glasshouse conditions. Leaves and roots were harvested 1 d before and 2, 4, 6, 8 and 10 d after the start of waterlogging treatment. Through comparing the activities of superoxide dismutase （SOD）, ascorbate peroxidase （APX）, glutathione reductase （GR）, catalase （CAT） and guaiacol peroxidase （POD） between waterlogging-tolerant and waterloggingsensitive genotype, we deduced that CAT was the most important H2O2 scavenging enzyme in leaves, while APX seemed to play a key role in roots. POD, APX, GR and CAT activities in conjunction with SOD seem to play an essential protective role in the O2^- and H2O2 scavenging process. Lipid peroxidation was enhanced significantly only in K12 （P 〈 0.001） and there was no difference （P 〉 0.05） in HZ32 up to 6 d after waterlogging stress. These results indicated that oxidative stress may play an important role in waterlogging-stressed maize plants and that the greater protection of HZ32 leaves and roots from waterlogging-induced oxidative damage results, at least in part, through the maintenance of increased antioxidant enzyme activity.

Antioxidant,lipid peroxidation inhibition and free radical scavenging efficacy of a diterpenoid compound sugiol isolated from Metasequoia glyptostroboides

Objective:To investigate the antioxidant enicacy of a biologically active dilerpenoid compound sugiol isolated from Metasequoia glyptostroboides(M.glyptostroboides)in various antioxidant models.Methods:An abietane type diterpenoid sugiol,isolated from ethyl acetate extract of M.glyptostroboides cones,was analyzed for its antioxidant efficacy as reducing power ability and lipid peroxidation inhibition as well as its ability to scavenge free radicals such as 1,1-diphenyl-2-picryl hydrazyl,nitric oxide,superoxide and hydroxyl radicals.Results:The sugiol showed significant and concentration-dependent antioxidant and free radical scavenging activities.Consequently,the sugiol exerted lipid peroxidation inhibitory effect by 76.3%as compared to a-tocopherol(80.13%)and butylaled hydroxyanisole(76.59%).In addition,the sugiol had significant scavenging activities of l,l-diphenyl-2-picryl hydrazyl,nitric oxide,superoxide and hydroxyl free radicals in a concentration-dependent manner by 78.83%,72.42%,72.99%and 85.04%,when compared to the standard compound ascorbic acid(81.69%,74.62%,73.00%and 73.79%)and a-tocopherol/butylated hydroxyanisole(84.09%,78.61%,74.45%and 70.02%),respectively.Conclusions:These findings justify the biological and traditional uses of M.glyptostroboides or its secondary metabolites as confirmed by its promising antioxidant efficacy.

Sperm lipid peroxidation and pro-inflammatory cytokines

Aim： To investigate if interleukin-6 （IL-6）, interleukin-8 （IL-8）, interleukin- 10 （IL-10）, interferon-gamma （IFN-γ） or tumor necrosis factor-alpha （TNF-α） are able to stimulate the level of lipid peroxidation of sperm membranes, either alone or in the presence of leukocytes. Methods： Semen samples from normozoospermic donors were prepared by density gradient. The sperms were exposed to the indicated cytokines, at physiological and infection-inflammation concentrations, in the absence or presence of leukocytes. Lipid peroxidation of the sperm membranes was determined by measuring malondialdehyde （MDA） and 4-hydroxialkenals （HAE） formation. Results： TNF-α, IL-8 and IFN-γ increased the level of sperm membrane lipid peroxidation when tested at physiological concentrations. At infectioninflammation concentrations, only IL-8 was able to produce a higher effect. When assayed in the presence of leucocytes, IL-8 and TNF-α showed a higher effect at infection-inflammation concentrations than at physiological concentrations. Finally, IL-8 showed a higher effect in the presence of leukocytes than in their absence at both physiological and infection-inflammation concentrations. TNF-α also showed a higher effect when assayed in the presence of leuko- cytes than in their absence, but only at infection-inflammation concentrations. There was no effect of IL-6 or IL-10 in any of the tested conditions. Conclusion： Several pro-inflammatory cytokines at physiological concentrations increase the level of lipid peroxidation of sperm membranes, which could be important for the sperm fecundation process. However, infection-inflammation concentrations of some cytokines, such as IL-8 and TNF-α, either alone or in the presence of leukocytes, could drive the lipid peroxidation of the spermatozoa plasma membrane to levels that can affect the sperm fertility capacity.

Lipid Peroxidation and Ultrastructural Modifications in Brain after Perinatal Exposure to Lead and/or Cadmium in Rat Pups

Objective To assess lipid peroxidation and ultrastructural modifications in rat brains following perinatal exposure to lead （Pb） and/or cadmium （Cd）. Methods Female rats were divided into four groups： control group, Pb （300 mg/L） group, Cd group （10 mg/L） and Pb＋Cd （300 mg/L, 10 mg/L） group. The compounds were delivered in the drinking water throughout pregnancy and lactation. Results The levels of compounds in blood and brain of the Pb＋Cd group were similar to those of other groups, but the effects of Pb＋Cd on pups＇ body and brain weights were higher than on other compounds. Electron microscopy revealed that Pb and Cd had effects on mitochondrial swelling, disruption and cristae loss, Nissl body dissolution, degenerated organelles and vacuoles, cytomembrane disappearance, and nuclear chromoplasm concentration. The activity of glutathione peroxidase （GSH-Px）, superoxide dismutase （SOD）, catalase （CAT）, acetylcholinesterase （ACHE） was decreased, whereas the activity of maleic dialdehyde （MDA） was increased. Conclusion Perinatal exposure to low doses of Pb and Cd can produce alterations in lipid peroxidation and ultrastructural modifications in rat brains, and exposure to both metals can result in greater damages.